Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 119 appraisals
Human vaccines & immunotherapeutics
Artificial intelligence in immune checkpoint inhibitor research: A bibliometric analysis of the landscape
This bibliometric analysis examines the transformative role of artificial intelligence (AI) in immune checkpoint inhibitor (ICI) research. Using VOSviewer, CiteSpace, and Bibliometrix, we analyzed 1,938 publications from the Web of Science Core Collection (2015-2026), revealing a dramatic rise in AI-related ICI studies, led by China and the USA. Key findings demonstrate AI's integration in predicting treatment response, optimizing dosing strategies, and managing immune-related adverse events. Through keyword co-occurrence and citation analyses, we identify critical AI applications including digital pathology and tumor microenvironment characterization. This comprehensive overview provides valuable insights into research trends and emerging frontiers for AI-driven innovations in cancer immunotherapy.
30 July 2026
Read appraisal →Blood advances
Successful gene therapy for transfusion-dependent α-thalassemia: a case report
α-Thalassemia is a severe inherited hemoglobin (Hb) disorder with limited curative options for patients with transfusion dependency, lacking suitable donors. We report, to our knowledge, the first-in-human application of lentiviral vector-mediated α-globin gene therapy in a girl aged 14 years with transfusion-dependent HbH disease (--SEA/αCSα). Autologous CD34+ hematopoietic stem and progenitor cells were mobilized, collected, and genetically modified ex vivo using the lentiviral vector (Lenti-HBA) to restore α-globin expression, then reinfused after busulfan conditioning. The patient achieved engraftment within 3 weeks and started to be free of transfusions from the fourth week onward. In the last year of follow-up (months 12-24), the average Hb level remained at ∼90 g/L without transfusion support, with HbA accounting for >85% of total Hb. Vector copy numbers were stable, and no evidence of clonal dominance, insertional mutagenesis, or replication-competent lentivirus was detected. Adverse events (AEs) were limited to expected busulfan-related toxicities, including grade 2 menstrual irregularity and ovarian failure (serious AE). Despite cessation of chelation therapy, iron overload progressed minimally, and no cardiac iron deposition occurred. Immune recovery, growth, and development were preserved. This case demonstrates the feasibility, safety, and durable efficacy of lentiviral α-globin gene therapy as a potential curative treatment for transfusion-dependent α-thalassemia. This trial was registered at www.clinicaltrials.gov as NCT05851105.
29 July 2026
Read appraisal →Journal of chemical information and modeling
Functionally Guided Graph Learning for Robust Cross-Patient Cell-Type Annotation in Single-Cell RNA Sequencing
Cross-patient cell-type annotation in single-cell RNA sequencing (scRNA-seq) remains challenging due to pronounced interpatient heterogeneity and distribution shifts across patient-specific cellular contexts. Conventional annotation approaches often rely on proximity-driven graph construction or expression similarity, which may introduce spurious cell-cell connections and lead to unstable knowledge transfer across patients. To address this limitation, we propose PathoGraph, a functionally guided graph learning framework for robust cross-patient cell-type annotation. The proposed method integrates KEGG-7-based biosemantic graph structure learning with cross-patient representation adaptation. Specifically, pathway-derived functional semantic profiles are incorporated to refine patient-specific cell graphs, encouraging biologically coherent neighborhoods and suppressing noise introduced by purely expression-based similarity. Based on the refined graphs, a cross-patient representation adaptation mechanism further aligns embeddings between labeled reference patients and unlabeled query patients to facilitate reliable annotation transfer. Experiments on three cross-patient scRNA-seq data sets, including leukemia, breast invasive carcinoma, and colorectal cancer data sets, demonstrate that PathoGraph achieves stable annotation performance across 32 directed reference-to-query transfer tasks. Across all tasks, PathoGraph obtained an average ACC of 84.28% and an F1-score of 84.08%, showing competitive and stable performance compared with representative marker-based, correlation-based, and model-based annotation methods. Ablation studies further show that removing the biosemantic graph learning module reduces the average accuracy to 83.48%, highlighting the importance of functional-guided graph refinement. In addition, post hoc functional relevance analyses in immune-cell and cancer-associated contexts suggest that the learned cell-cell graphs capture biologically relevant neighborhood structures beyond expression-driven proximity. The source code and processed data are publicly available at: https://github.com/LiYuechao1998/PathoGraph.
29 July 2026
Read appraisal →New biotechnology
Harnessing AI to decode protein kinases: Structural, functional, and therapeutic design perspectives.
Recent advances in Artificial Intelligence (AI) are reshaping kinase research by uncovering complex regulatory mechanisms and accelerating drug discovery. These advances have enabled the capture of elusive allosteric transitions and transient cryptic pockets by exploring dynamic conformational landscapes, revealing features critical for understanding ligand interactions and enzymatic regulation. AI-driven structure prediction tools, such as AlphaFold (AF)-based models, offer high-resolution insights into kinase conformations and complex assembly, thereby clarifying receptor activation in signaling pathways. Moreover, cutting-edge AI frameworks provide fresh perspectives on substrate prediction, cofactor mapping, and mutation-induced structural changes. Integrative strategies that combine Machine Learning (ML), molecular docking, Molecular Dynamics (MD) simulation, and experimental validation have further streamlined the discovery of novel kinase inhibitors and related studies. Collectively, these AI-enhanced approaches deepen our understanding of kinase-mediated signaling-from developmental processes to oncogenic transformation-and highlight the powerful synergy between computational and experimental research in advancing therapeutic innovations.
25 July 2026
Read appraisal →Cell reports. Medicine
Toward generalizable prediction of cancer signal using a cell-free DNA language model.
Cell-free DNA can be used for early cancer detection, minimal residual disease monitoring, and post-treatment risk stratification. However, current assays are often designed for a single purpose and rely on deep or broad sequencing panels that capture only a small fraction of tumor-derived signals, limiting transferability, increasing cost, and reducing scalability. Fragmentia-AI is an artificial intelligence language model that learns fragment-level sequence patterns in tumor-derived cell-free DNA. Instead of focusing on mutations, it uses the structure of cell-free DNA to detect cancer signals in a partially panel-agnostic manner from ultra-low sequencing input, approximately 0.1%-1% of conventional depth. The model performs well across cancer types and clinical settings, including monitoring after surgery or immunotherapy, and in samples with low variant allele frequencies or no detected mutations. Fragment-level analyses identify shorter fragments and tumor-derived sequence patterns across panels of different sizes and ultra-low-pass whole-genome sequencing in multiple cohorts.
23 July 2026
Read appraisal →Nucleic acids research
DeepKinomeWeb: a quantitative, panel-level platform for kinase inhibitor screening and selectivity profiling
Protein kinases are central targets in drug discovery, yet early-stage development of potent and selective inhibitors remains challenging due to high experimental costs and limited interpretability of large-scale screening data. Here, we present DeepKinomeWeb, an integrated web-based platform that transforms competition-based high-throughput screening data into actionable insights for kinase inhibitor prioritization. Built upon our previously validated deep learning regression model, DeepKinome, the platform enables quantitative prediction of kinase-inhibitor binding affinities and provides panel-level visualization of selectivity landscapes, selectivity metric calculations, and integrated structural and physicochemical analyses. Through its user-friendly interface, DeepKinomeWeb supports rational, data-driven decision-making for biologists and medicinal chemists, lowering the barrier to systematic selectivity assessment in kinase inhibitor discovery. DeepKinomeWeb is freely available to all users without any login requirement at https://str.kribb.re.kr/deepkinome.
13 July 2026
Read appraisal →Molecular pharmaceutics
Platelets as Programmable Drug Depots: Toward Predictive and Mechanistic Drug Loading
Efficient drug delivery remains a major challenge in pharmaceutical science, with synthetic nanocarriers often facing limitations in real biological systems. While blood platelets have been explored as biomimetic carriers, their intrinsic capacity for molecular storage and stimulus-triggered release remains largely underutilized. Here, we propose that platelet granules can be viewed as programmable drug depots, whose loading can be rationally controlled using physicochemical principles and endogenous transport mechanisms. In contrast to empirical approaches, we outline a framework based on two complementary pathways: passive accumulation driven by ion trapping of weakly basic compounds in acidic granules, and active uptake mediated by vesicular transporters. Building on recent advances in structural biology and computational modeling, we further argue that drug loading into platelets can be predicted and optimized using molecular descriptors, docking approaches, and machine learning models to estimate transporter compatibility and accumulation efficiency. This perspective introduces a conceptual design loop linking prediction and molecular optimization─i.e., enabling both selection of suitable drug candidates and rational modification of their structures to enhance platelet compatibility. Together, these concepts position platelets not simply as biomimetic carriers but as model-guided and engineerable platforms for drug delivery, bridging biological systems with rational design strategies.
6 July 2026
Read appraisal →Journal of hematology & oncology
Emerging artificial intelligence advances in oncology: latest updates from the 2026 AACR annual meeting.
Advances presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting highlight a shift from standalone artificial intelligence (AI) models to integrated, agentic systems across oncology. Platforms such as Synapse enable large-scale data coordination, supporting interoperable and reproducible research. Building on this foundation, conversational and multi-agent AI tools (e.g., DrBioRight, GP CoPilot, Isabl AI Agent) allow natural language interaction with multimodal cancer data, lowering technical barriers. Agentic frameworks for real-world data (RWD) transformation, including clinical document abstraction, cohort extraction, and social determinants of health (SDOH) analysis, demonstrate high accuracy and scalability, while self-critical systems improve reliability. Clinically, AI shows growing impact through validated imaging biomarkers, enhanced trial matching, and scalable cohort identification. In parallel, multi-agent systems are accelerating therapeutic discovery, including CAR-T development and immunotherapy target identification. Collectively, these advances position AI as an active, collaborative partner in cancer research and precision oncology.
5 July 2026
Read appraisal →Lancet (London, England)
Diagnosis and treatment of postpartum haemorrhage: a race against time.
Postpartum haemorrhage (PPH) is common, affecting an estimated 13% of women having vaginal birth and 31% of women having caesarean birth. Successful management of PPH requires early and accurate diagnosis and effective treatment. A systematic review found that subjective visual estimation of blood loss misses 52% of PPH diagnoses at vaginal birth (pooled sensitivity 48%, 95% CI 44-53), and probably more at caesarean birth. The WHO-International Federation of Gynecology and Obstetrics-International Confederation of Midwives consolidated guidelines on PPH therefore recommend objective quantification of blood loss with products such as a calibrated blood collection drape. When supported by a robust implementation strategy and a first-response treatment bundle, objective measurement of blood loss and monitoring of vital signs has been shown to diagnose PPH accurately and early, and improve clinical outcomes. Refractory PPH can progress to life-threatening PPH, which should be managed by a multidisciplinary team providing aggressive resuscitation and targeted treatment. Saving the life of a woman with excessive postpartum bleeding is a race against time. The six delays to avoid are: (1) in the diagnosis (by use of objective cumulative blood loss measurement and early trigger criteria), (2) in the first-response treatment (by authorising midwives to administer all components of a standardised bundle of interventions), (3) in the escalation (by use of explicit escalation criteria and red flags), (4) in the use of temporising measures (eg, non-pneumatic anti-shock garment), (5) in the identification and targeted management of any specific causes of bleeding, and (6) in the provision of blood and blood products. Quick actions to avoid these delays can mean the difference between life and death for a woman with PPH.
4 July 2026
Read appraisal →Journal of hematology & oncology
Large language model-guided CAR-T in silico platform for cytokine optimization in liver cancer with low antigen density
CAR-T cell therapy has shown remarkable success in hematologic malignancies but remains limited in solid tumors such as liver cancer due to antigen heterogeneity, low target antigen density, and an immunosuppressive tumor microenvironment (TME). Cytokine engineering can enhance CAR-T persistence and effector function; however, the optimal cytokine payload may vary depending on tumor type, target antigen expression level, and microenvironmental context, making systematic experimental comparison time-consuming and labor-intensive. Here, we applied a large language model (LLM)-based CAR-T in silico platform to systematically evaluate cytokine engineering strategies, including IL-2, IL-7, IL-12, IL-15, and IL-18, in glypican-3 (GPC3)-targeted CAR-T cells for liver cancer. We used cytokine selection as a biologically grounded benchmark to test whether the platform could recover known CAR-T cell-relevant cytokine biology and support future novel predictions. Computational predictions identified IL-15 as the most effective enhancer, particularly against tumor cells with low GPC3 expression. Guided by these results, we generated cytokine-armored GPC3 CAR-T cells and performed in vitro and in vivo validation. IL-15-engineered CAR-T cells exhibited superior proliferation, persistence, and serial cytotoxicity against GPC3-low liver cancer cells. In human liver cancer xenograft models, IL-15-enhanced CAR-T cells achieved improved tumor control compared with conventional and other cytokine-engineered CAR-T cells. The recovery of IL-15 served as a positive benchmark supporting the validity of the LLM-guided CAR-T in silico workflow. Collectively, this study establishes an LLM-guided framework, schema-constrained for rational cytokine selection in CAR-T engineering and identifies IL-15 as a potent enhancer for targeting antigen-low liver cancers.
3 July 2026
Read appraisal →Open biology
Deep learning in tumour genomics: from multi-omics integration to precision oncology
Cancer remains a leading cause of death globally, with nearly 10 million deaths in 2020. Advances in genomic technologies have revolutionized cancer research, shifting focus towards precision medicine based on comprehensive tumour genomic profiling. Concurrently, deep learning (DL) has emerged as a powerful paradigm for complex biological data. This review critically assesses recent advances in DL applications for tumour genomics, emphasizing four key domains: DNA sequencing analysis for mutation detection, gene expression profiling for cancer subtype classification, methylation function prediction for epigenetic characterization and integrative multi-omics approaches for comprehensive tumour profiling. We systematically analyse how different DL architectures-including convolutional neural networks, recurrent neural networks, graph neural networks, autoencoders and transformers-address specific challenges in cancer genomics. Our review highlights how these approaches significantly enhance detection sensitivity for genomic alterations, improve cancer subtype stratification, identify novel biomarkers and optimize therapeutic target selection. We examine technical challenges in DL implementation, including model interpretability, data scarcity, computational requirements and integration issues, alongside emerging solutions such as explainable AI, federated learning, and multi-modal frameworks. By synthesizing methodological innovations and identifying research directions, this review provides bioinformaticians and cancer researchers with a roadmap for leveraging DL to advance precision oncology.
2 July 2026
Read appraisal →BMJ supportive & palliative care
Time toxicity of patients with cancer enrolled in clinical trials: a systematic review and meta-analysis
PURPOSE: Time toxicity-the time patients spend receiving treatment, managing side effects, attending follow-ups and undergoing rehabilitation-is increasingly recognised as an important burden of cancer care. While time toxicity has been studied in routine clinical settings, it has rarely been quantified among patients with cancer enrolled in pharmacotherapy clinical trials. This systematic review aims to quantify time toxicity in this population. DESIGN: We searched Ovid MEDLINE, Embase and Cochrane CENTRAL from inception to 12 June 2025. Studies were included if they reported time toxicity among patients with cancer enrolled in clinical trials. Time toxicity was defined as calendar days with healthcare contact. Primary outcomes were (1) total days, (2) planned days and (3) unplanned days per month. Study quality was assessed using the Joanna Briggs Institute's (JBI) Checklist for Cohort Studies. RESULTS: Four retrospective studies reporting on an aggregate of 1809 patients were included. Two studies had low risk for bias and two had unclear risk of bias. Patients experienced time toxicity a mean of 7.6 days per month, with the highest burden in the first month of trial participation. Planned and unplanned days averaged 2.2 and 2.0 days per month, respectively. The ratio of planned to unplanned days remained consistent over time. CONCLUSIONS: Time toxicity is a substantial, under-recognised burden in cancer pharmacotherapy trials-approximately two times that experienced by non-participants. Its measurement and mitigation should be prioritised to improve patient-centred care, support shared decision-making and inform trial design, policy and consent processes. REGISTRATION: Study protocol preregistration: https://doi.org/10.17605/OSF.IO/BVY7C.
1 July 2026
Read appraisal →Genome biology
MLMarker: a machine learning framework for tissue inference and biomarker discovery
MLMarker is a machine learning tool that computes continuous tissue similarity scores for proteomics data, addressing the challenge of interpreting complex or sparse datasets. Trained on 34 healthy tissues, its Random Forest model generates probabilistic predictions with SHAP-based protein-level explanations. A penalty factor corrects for missing proteins, improving robustness for low-coverage samples. Across three public datasets, MLMarker revealed brain-like signatures in cerebral melanoma metastases, achieved high accuracy in a pan-cancer cohort, and identified brain and pituitary origins in biofluids. MLMarker provides an interpretable framework for tissue inference and hypothesis generation, available as a Python package and Streamlit app.
26 June 2026
Read appraisal →PloS one
Artificial intelligence in the diagnosis of deep vein thrombosis: A scoping review
Deep vein thrombosis (DVT) is the formation of thrombi in the deep venous system, most often in the lower extremities. Although usually not life-threatening, DVT requires timely diagnosis to prevent complications such as pulmonary embolism and post-thrombotic syndrome. The growing demand for image interpretation has generated interest in applying artificial intelligence (AI) to automated DVT detection. This scoping review analyzes the performance of artificial intelligence in diagnosing DVT using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). We conducted a search across seven databases from inception to May 2025 using terms related to deep vein thrombosis, artificial intelligence, and machine learning. Eligible studies were limited to those evaluating DVT diagnosis using CT, MRI, or ultrasound. Two independent reviewers selected eligible studies, and quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Eleven studies published between 2021 and 2025 met the inclusion criteria. Some of the AI algorithms included RetinaNet, Deep R-Belief Neural Networks, and Sooty Tern Optimization. US-based models were the most studied algorithms, with sensitivities and specificities ranging from 68 to 100% and 70-100%, respectively. The MRI-based model achieved sensitivities, specificities, and accuracies of 95% to 97%. One CT-based model demonstrated a sensitivity of 83%. Studies evaluated across multiple imaging datasets showed high sensitivities, specificities, and precision of 96% or higher. Future research should prioritize multicenter validation and integration of clinical factors. In addition, explainable frameworks capable of integrating multiple imaging datasets must be developed with attention to workflow efficiency and cost-effectiveness to support clinical translation. The results indicate that AI is best situated as a supplementary tool rather than a replacement for expert interpretation in DVT diagnosis.
23 June 2026
Read appraisal →Journal of chemical information and modeling
GraFSyn: An Interpretable Deep Learning Framework for Anticancer Drug Synergy via Graphlet Fingerprints
Predicting drug synergy is important for accelerating the discovery of effective anticancer combination therapies. Synergy intrinsically depends on the precise interactions of key chemical substructures within specific cellular environments. However, current molecular graph-based computational methods typically rely on implicit atom-level feature aggregation, which may obscure the topological representation of critical chemical substructures and limit structural traceability. Therefore, we present Graphlet Fingerprint-based Synergy prediction (GraFSyn), a deep learning framework for anticancer drug synergy prediction that uses graphlet fingerprints to encode drugs as explicit connected substructure units, preserving predefined chemical substructures and their topological identity. We further introduce a Dynamic Multi-Scale Convolution (DMSC) module to learn informative representations from high-dimensional and sparse graphlet features. The framework also includes an interaction module to capture context-dependent interactions between drug substructures and cell line gene expression. On the Merck and AstraZeneca benchmark data sets, GraFSyn achieved ROC-AUC/PR-AUC values of 0.972/0.912 and 0.823/0.906, respectively, outperforming representative baseline methods. In addition, attributed signals can be mapped back to specific pharmacophoric regions, supporting substructure-level analysis of synergistic interactions. In general, GraFSyn provides an accurate and structurally traceable approach for anticancer drug combination screening.
23 June 2026
Read appraisal →Journal of chemical information and modeling
Generative Artificial Intelligence Optimization of Albumin Binders: Coumarin and Fatty Acid Derivatives
Previously, we reported a dual combination based on 4-hydroxycoumarin and dodecanedioic acid that could synergistically bind to human serum albumin (HSA). However, optimizing this combination remains challenging and could often be guided by empirical selection and extensive experimental screening, which may limit the chemical diversity and suboptimal affinity. In this study, we established a systematic artificial intelligence framework that integrates computational optimization with wet-lab synthesis and experimental validation, enabling improvement of the dual combination while preserving the core chemotypes. We first trained a machine learning classifier on curated HSA binding data and used it as an external scoring function to guide reinforcement learning-driven scaffold decoration with LibINVENT, enabling goal-directed generation of coumarin derivatives and fatty acid derivatives. Candidate molecules were prioritized through multiparameter filtering and diversity-aware selection, followed by synthesis and experimental validation using surface plasmon resonance. The optimized representatives show nanomolar HSA binding and enhanced affinity compared to the original ligands. Molecular docking and molecular dynamics simulations further provide a mechanistic rationale for the affinity improvements by revealing additional stabilizing interactions and more favorable binding energetics at the corresponding HSA sites. Besides, the optimized coumarin derivative (CD1) is a warfarin-derived coumarin analogue, yet it did not show detectable anticoagulant activity in an acute clotting time assay, whereas warfarin did. Overall, this work demonstrates a practical AI-guided route to expand chemical diversity and improve affinity for a synergistic HSA binding combination.
23 June 2026
Read appraisal →Analytica chimica acta
Rapid detection of drug-resistant leukemia cell using an optofluidic chip and machine learning
BACKGROUND: Rapid detection of drug-resistant leukemia played a crucial role in formulating appropriate treatment plans for patients and improving their prognosis. In this research, an integrated optofluidic platform was developed to detect and analyze leukemia and drug-resistant leukemia cell. The detection technique was designed by embedding optical fibers coupled with photosensors and a laser source into optofluidic chip. The scattered light signals were detected when the cells pass through the detecting area. RESULTS: The platform was first validated by classifying 1 μm polystyrene microparticles and 1 μm polystyrene microparticles coated with spherical 10 nm Fe3O4 nanoparticles. After validation, the method was applied to classify leukemia and drug-resistant leukemia cells by injecting the testing sample and obtaining. The SVM classifier demonstrated the highest classification accuracy of 91.1% compared with LR, RF, and KNN classifiers for analyzing leukemia cells and drug-resistant leukemia cells. The proposed method can perform detection within 10 min with a total experimental timeframe of 20 min. SIGNIFICANCE: The presented results demonstrate the feasibility of applying microfluidics and machine learning approaches to detect and classify biological entities with slight variations based on scattered light signals. This platform holds significant potential for clinical diagnostics, offering a rapid, cost-effective, and efficient method for detecting drug-resistant leukemia cells, potentially aiding in personalized treatment strategies.
16 June 2026
Read appraisal →The Cochrane database of systematic reviews
Bone marrow-sparing radiotherapy in women with cervical cancer treated with radiochemotherapy
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary objective To evaluate the benefits and harms of bone marrow-sparing radiotherapy compared with non-bone marrow-sparing radiotherapy in women with locally advanced cervical cancer treated with concurrent chemoradiotherapy. Secondary objectives To investigate whether effects differ according to clinical, histopathological, and technical characteristics, focusing on: acute haematologic toxicity; acute gastrointestinal and genitourinary toxicity; and bone marrow dose-volume parameters associated with acute haematologic toxicity, including exploration of dose-volume ranges relevant for clinical implementation.
13 June 2026
Read appraisal →Blood
Fixed-duration VenO vs FCR/BR in fit patients with untreated CLL: primary analysis of the phase 3 CRISTALLO trial
The phase 3 CRISTALLO trial compared first-line fixed-duration venetoclax-obinutuzumab (VenO) vs fludarabine, cyclophosphamide, and rituximab (FCR)/bendamustine-rituximab (BR) in patients with chronic lymphocytic leukemia (CLL), using undetectable minimal residual disease (uMRD) as the sole primary end point. Previously untreated patients with a cumulative illness rating scale score ≤6 and creatinine clearance ≥70 mL/min without del(17p)/TP53 mutations were randomized 1:1 to VenO or FCR/BR. The primary end point was uMRD (<10-4) in peripheral blood (PB) using next-generation sequencing at month 15. Key secondary end points included uMRD (<10-4) in PB and bone marrow (BM) at end of treatment (EOT) and progression-free survival (PFS). uMRD at deeper cutoffs were explored. At data cutoff (19 March 2024), 80 patients received VenO, and 86 received FCR/BR. Baseline characteristics were generally balanced across arms. The primary end point was met: 81.3% (VenO) and 54.7% (FCR/BR) achieved uMRD (<10-4) in PB at month 15 (P = .0004). uMRD (<10-4) in PB and BM at EOT was also higher with VenO vs FCR/BR. Short follow-up precluded evaluation of PFS at the first planned interim analysis; however, fewer patients progressed/died with VenO vs FCR/BR (7 vs 13). At month 15, 65.0% (VenO) and 25.6% (FCR/BR) achieved uMRD (<10-6) in PB. The overall safety profile was consistent with the known safety profile of each drug. No patient in the VenO arm was deemed high risk for tumor lysis syndrome (TLS) after obinutuzumab debulking; no clinical TLS occurred. These results confirm and extend the findings from the GAIA-CLL13 trial, validating increased depth of response with VenO vs chemoimmunotherapies. This trial was registered at www.clinicaltrials.gov as NCT04285567.
13 June 2026
Read appraisal →Developmental cell
A machine learning-based megakaryocyte identification system uncovers resident organs, markers, and functional diversity
The organ- and stage-specific diversity of megakaryocytes (MKs) has prompted a reassessment of their distribution and functions. By integrating single-cell transcriptomic data across multiple organs and developmental stages, we identified previously unreported MK and platelet markers, including Tnik, a key regulator of MK function and platelet production. Using these markers alongside established ones, we developed a machine learning-based MK identification system (MKIDS) that enables MK detection in the brain, heart, and placenta in mice and humans. Functional studies demonstrated that brain-resident MKs are essential for neural development, underscoring organ-specific roles of MKs in regulating tissue development and function. Transcriptomic integration of MKs across organs and stages, with functional validation, revealed a developmental shift in platelet production-from a mitochondria-low to a mitochondria-enriched subpopulation. Our findings offer a transformative perspective on the MK system, highlighting its cellular diversity, functional complexity, and developmental dynamics.
12 June 2026
Read appraisal →Blood advances
A phase 1/2 study of duvelisib plus venetoclax in patients with relapsed/refractory CLL/SLL or Richter transformation
In this phase 1/2 study we evaluated duvelisib plus venetoclax in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Richter transformation (RT). Venetoclax was added after 1 week of duvelisib. After 1 year of therapy, patients with a complete response (CR) and undetectable minimal residual disease (uMRD) could discontinue therapy; patients with detectable MRD continued venetoclax monotherapy until 2 separate occasions of uMRD. Thirty five patients with CLL/SLL and 9 with RT enrolled. Among patients with CLL, 77% had unmutated immunoglobulin heavy chain variable region, 46% had TP53 aberrancy, and patients had a median of 2 prior therapies, including 60% with prior Bruton tyrosine kinase inhibitor. In phase 1 the maximum tolerated dose was not reached, and the recommended phase 2 dose was 25mg twice daily duvelisib plus 400mg daily venetoclax. 91% of patients experienced ≥grade 3 neutropenia, with febrile neutropenia in 6%. Common nonhematologic toxicities were diarrhea (63%, 14% ≥grade 3) and elevated aspartate aminotransferase (51%, 9% ≥grade 3). The best CR and overall response rates were 60% and 91%, respectively. At cycle 13, peripheral blood and bone marrow uMRD at 10-4 were 43% and 40%, respectively. The median progression-free survival (PFS) for patients with CLL/SLL was 46 months, and the 3-year PFS was 67% (95% confidence interval, 0.51-0.86). Four patients with RS achieved a response (3 CRs). Overall, duvelisib plus venetoclax was active in R/R CLL/SLL and RT, although serious adverse events occurred, including immune-mediated toxicities. This trial was registered at www.clinicaltrials.gov as NCT03534323.
9 June 2026
Read appraisal →Blood advances
Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia
Acalabrutinib is a selective, covalent Bruton tyrosine kinase inhibitor approved for marketing in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report final, long-term phase 1/2 study results in 99 patients with treatment-naive (TN) and 134 with relapsed/refractory (R/R) CLL/SLL. At final data cutoff, 71% and 31% of patients in the TN and R/R cohorts, respectively, remained on acalabrutinib treatment (median follow-up of 73.7 and 52.6 months). Among the events of clinical interest (any grade) in the TN and R/R cohorts, atrial fibrillation was reported in 6.1% and 9.0%, hypertension in 29.3% and 23.1%, other malignancies (excluding nonmelanoma skin cancer) in 14.1% and 17.2%, and major bleeding in 8.1% and 8.2% of patients, respectively. The incidence of the most common adverse events decreased over time. Overall response rates were 97.0% and 94.8% in the TN and R/R cohorts, respectively, with similar response findings among patients with standard and high-risk genomic features. In the TN cohort, median progression-free survival (PFS) was not reached and the 72-month PFS rate was 86.7% (95% confidence interval [CI], 77.0-92.5). For the R/R cohort, median PFS was 66.1 months (range, 0.4-87.8) and the 72-month PFS rate was 45.1% (95% CI, 35.6-54.1). This final analysis extends the duration of benefit observed with acalabrutinib, demonstrates that no new safety signals are apparent with longer follow-up, and confirms the safety and tolerability of acalabrutinib monotherapy for patients with CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02029443.
9 June 2026
Read appraisal →Blood advances
Ropeginterferon alfa-2b for prefibrotic myelofibrosis and lower-risk myelofibrosis requiring cytoreduction
There is currently no consensus on the optimal treatment of early myelofibrosis (MF). Ropeginterferon alfa-2b (ropeg) is a next-generation monopegylated interferon alfa-2b developed specifically to treat myeloproliferative neoplasms. We conducted a phase 2 study in patients with prefibrotic primary MF (pre-PMF) and Dynamic International Prognostic Scoring System low-/intermediate-1-risk fibrotic PMF or secondary MF (SMF) who required cytoreduction. Ongoing treatment with hydroxyurea was substituted with ropeg (week 0, 250 μg; week 2, 350 μg; week 4 onward, 500 μg every 2 weeks). The primary end points were safety and clinicohematologic complete response (CHCR). Seventy-one patients (40 men and 31 women) with a median age of 60 years (range, 31-86) were enrolled and followed up for a median of 119 weeks (range, 10-131). At weeks 24, 48, and 104, CHCR was achieved in 63.8% (pre-PMF, 74%; fibrotic PMF, 20%; fibrotic SMF, 42.9%), 63.5% (pre-PMF, 69.6%; fibrotic PMF, 25%; SMF, 53.9%), and 70% of patients (pre-PMF, 78.4%; fibrotic PMF, 33.3%; SMF, 50%), respectively. Thrombo-hemorrhagic events were not observed after stopping hydroxyurea. At weeks 24, 48, and 104, reduction in JAK2V617F variant allele frequency (VAF) was observed in 53.1%, 70%, and 67.6% of patients, and reduction in CALR mutant VAF was observed in 52.6%, 42.9%, and 40% of patients, respectively. In 50 evaluable cases at week 104, 13 patients (26%) had reduced bone marrow reticulin fibrosis. There were 3 treatment discontinuations (4.2%) due to adverse events. In conclusion, ropeg was safe and induced CHCR associated with significant molecular responses in patients with early MF. This trial was registered at www.clinicaltrials.gov as NCT04988815.
9 June 2026
Read appraisal →Neurology
Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease
BACKGROUND AND OBJECTIVES: Adults with sickle cell disease (SCD) are at risk of decline in brain health and cognition, even without clinical stroke. SCD-related changes on MRI include brain atrophy and T2 fluid attenuated inversion recovery (FLAIR) white matter hyperintensity (WMH) growth. Hematopoietic stem cell transplant (HSCT) can be curative, but conditioning regimens risk new complications, particularly for adults with accumulated organ damage. We tested whether successful HSCT for adults with SCD was associated with reduced brain atrophy or WMH growth. METHODS: In this cohort study, adults with severe SCD underwent HSCT as part of 5 research protocols at the National Institutes of Health Clinical Center, including autologous gene therapy, HLA-matched donor HSCs, and haploidentical HSCs. Serial brain MRI scans acquired before and after transplant for up to 12 years included 3D T1-weighted and axial FLAIR sequences. Longitudinal brain volumes, segmented using FreeSurfer and corrected for total intracranial volume (TICV), were used to measure brain parenchymal fraction (BPF). A deep learning algorithm segmented WMH volumes from FLAIR sequences. Volumes were log2-transformed as a percentage of TICV. We tested whether HSCT success (persistent engraftment vs graft failure) or change in hemoglobin (Hb) (post-pre-HSCT) was associated with the rate of brain atrophy or WMH growth using mixed-effects linear regression. Random effects included scanner, participant intercept, and slope, while fixed effects included age and sex. RESULTS: Seventy-seven participants (mean age 32 ± 9 years, 43% female) who underwent HSCT were followed for a median 5.3 years (interquartile range [IQR] = 4.6). For 65 participants with successful HSCT, BPF declined nonsignificantly (-0.055%/year; 95% CI -0.12, 0.006; p = 0.08). Twelve participants with graft failure had a 7-fold greater BPF decline (-0.42%/year; 95% CI -0.57, -0.26; p < 0.001; group difference p < 0.001). A smaller change in Hb after HSCT was associated with steeper BPF decline (0.035%/year per unit Hb; 95% CI 0.017, 0.053; interaction p < 0.001). WMH growth was similar in both groups (0.038% vs 0.030% per year; interaction p = 0.50) and was associated with older age and baseline WMHs, but not treatment success. DISCUSSION: Successful HSCT was associated with preserved brain volume, but not WMH growth, another brain health biomarker. Whether these HSCT-related brain structural changes translate to cognitive preservation remains to be determined. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT02140554 registered 2014-05-14, first enrollment February 2015; ClinicalTrials.gov NCT00061568; registered 2004-07-16, first enrollment July 2004; ClinicalTrials.gov NCT02105766; registered 2014-04-01, first enrollment April 2014; ClinicalTrials.gov NCT03077542; registered 2017-03-10, first enrollment April 2017; ClinicalTrials.gov NCT00977691; registered 2009-12-14, first enrollment December 2009. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in adults with sickle cell disease, successful hematopoietic stem cell transplant is associated with slower declines in BPFs over a median period of 5 years, compared with patients with transplant failure.
9 June 2026
Read appraisal →Blood advances
Phase 1 study of zanubrutinib plus lenalidomide for patients with relapsed/refractory diffuse large B-cell lymphoma
Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) typically have a poor prognosis. In preclinical studies, lenalidomide and a Bruton tyrosine kinase (BTK) inhibitor demonstrated synergistic antitumor effects. Zanubrutinib, a next-generation BTK inhibitor, has greater selectivity to minimize off-target binding. BGB-3111-110 was a phase 1 multicenter dose-escalation/-expansion study. Patients with R/R DLBCL received zanubrutinib 160 mg twice daily plus lenalidomide (15, 20, or 25 mg once daily) until progression or unacceptable toxicity. Primary end points were safety, recommended phase 2 dose (RP2D), and overall response rate (ORR; Lugano 2014 criteria). Sixty-six patients were enrolled and treated. Patients had a median of 2 previous therapies, 83% had stage III/IV disease, and ∼67% had non-geminal center B-cell-like or activated B-cell-like DLBCL. No dose-limiting toxicities occurred; the lenalidomide RP2D was 25 mg once daily when combined with zanubrutinib 160 mg twice daily. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 74%; the most common (>20%) grade ≥3 TEAEs were decreased neutrophil count (58%) and decreased white blood cell count (29%). TEAEs led to 7 treatment discontinuations (11%) and 2 deaths (3%). At the RP2D, ORR and complete response rate were 58% and 42%, respectively; median time to response was 2.8 months. Median duration of response was 14.9 months. Median progression-free survival was 5.5 months (95% confidence interval [CI], 2.9-11.1); the 12-month event-free rate was 34% (95% CI, 21-48). Zanubrutinib plus lenalidomide demonstrated acceptable tolerability and antitumor activity in patients with R/R DLBCL. This trial was registered at www.clinicaltrials.gov as NCT04436107.
9 June 2026
Read appraisal →Blood advances
Accurate identification of sickle cell disease cases in a large genotyped cohort using electronic health record data
The US Food and Drug Administration recently approved sickle cell disease (SCD) gene therapies that require a contemporaneous cohort to compare their outcomes with those of individuals who did not receive gene therapy. Previously, we developed an automated algorithm to create a contemporaneous cohort of children and adults with SCD using electronic health record data. We tested the hypothesis that the updated Vanderbilt University Medical Center (VUMC) algorithm can identify individuals with SCD with sensitivity and specificity of >95%. In the VUMC health care system, we identified a cohort of 33 141 adults and children of primarily African ancestry who underwent β-globin gene sequencing, with a 1.4% prevalence of SCD (473/33 141). For SCD, the performance of the VUMC algorithm using International Classification of Diseases (ICD) and laboratory data showed a sensitivity of 97.6% (462/473), specificity of 99.9% (32 663/32 668), positive predictive value of 98.9% (462/467), and negative predictive value of 99.9% (32 663/32 674). Three SCD phenotypes account for 98.5% of the individuals in the cohort. The cohort had sensitivities of 96.8% (272/281), 93.7% (136/145), and 85% (34/40) for hemoglobin SS (HbSS)/Hb Sβ0-thalassemia (HbSβ0), HbSC, and HbSβ+, respectively. The cohort had a specificity of 99.9% across all 3 phenotypes: HbSS/HbSβ0, HbSC, and HbSβ+, respectively. We have developed an updated algorithm using ICD and laboratory data that accurately identifies individuals with SCD within a large health care system, and distinguishes HbSS/HbSβ0, HbSC, and HbSβ+.
9 June 2026
Read appraisal →Blood advances
FDG-PET medullary total tumor volume highlights high-risk patients with newly diagnosed multiple myeloma in CASSIOPEIA trial.
This study aimed to assess the prognostic value of medullary total metabolic tumor volume (mTMTV) derived from fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) compared with conventional PET-derived features and biological/chromosomal abnormalities in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab for induction/consolidation and/or maintenance and enrolled in CASSIOPET, a companion study of CASSIOPEIA, with long-term follow-up. Automated bone/liver CT-based segmentation were applied to the baseline [18F]FDG-PET images, with mTMTV being defined using the median liver background as the cut-off, including focal lesions and diffuse bone marrow (BM) involvement. Both univariate/multivariate Cox and machine learning (ML)-based survival models were performed. A total of 195 patients were included, 81% of them PET-positive. Multivariate analysis demonstrated independent prognostic value of mTMTV for progression-free survival (PFS) (P< .001) and overall survival (OS) (P< .001), complementary to Revised International Staging System (R-ISS) (P = .008 and P< .001, respectively). The ML model confirmed these findings, achieving concordance index of 0.609 and 0.659 and identifying mTMTV as the most informative feature for PFS and OS. Adding R-ISS, BM maximum standardized uptake value (SUVmax) and anemia to mTMTV accounted for >60% of the ML model explanation for PFS and adding R-ISS, the number of focal lesions and BM SUVmax for >60% of the model for OS. Combining R-ISS and mTMTV enabled the creation of 2 new-risk subgroups. In conclusion, this prospective study demonstrated the prognostic relevance of [18F]FDG-PET/CT-based parameters in the initial workup of patients with NDMM in the era of anti-CD38-based therapy. mTMTV was found to have strong independent prognostic value, complementary to R-ISS and refining risk stratification. This trial was registered at www.clinicaltrials.gov as #NCT02541383.
9 June 2026
Read appraisal →Blood advances
A pilot randomized clinical trial of a peer support intervention for hematopoietic stem cell transplantation
Peer support has been associated with improved patient-reported outcomes (PROs), including reduced psychological distress, among patients undergoing hematopoietic stem cell transplantation (HSCT), but structured interventions are limited. This study assessed the feasibility, acceptability, and preliminary effects of a scalable peer support intervention to reduce psychological distress and enhance quality of life (QOL) post-HSCT. We conducted a pilot randomized clinical trial evaluating the Supporting Transplant Experiences with Peer Program (STEPP), a 5-session, telephone-based intervention delivered by an HSCT survivor offering psychoeducation and coping strategies. Participants were recruited 1 to 2 weeks pre-HSCT admission and randomized to STEPP or usual care. Feasibility was defined as ≥60% enrollment and ≥60% completing ≥3 sessions. Acceptability was assessed using the Client Satisfaction Questionnaire (CSQ; ≥3/4 mean benchmark). PRO measures of anxiety, depression (Hospital Anxiety and Depression Scale), posttraumatic stress (Post-Traumatic Stress Disorder Checklist-Civilian Version), QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplant), social support (Social Support and Effectiveness Questionnaire), and self-efficacy (Cancer Self-Efficacy Scale) were assessed pre-HSCT and at 30 and 60 days post-HSCT. Mixed-effects models explored preliminary effects. We enrolled 77% (90 of 117) of eligible patients (STEPP, n = 45; usual care, n = 45); 12 became ineligible due to HSCT cancellation or postponement. Among 78 active participants (mean age, 58.9 years [standard deviation, 12.3]; 57.7% women), all STEPP participants completed ≥3 sessions, and the mean CSQ score was 3.5. STEPP showed small-to-moderate improvements in day 30 anxiety (d = -0.36) and day 60 anxiety (d = -0.58), depression (d = -0.25), posttraumatic stress (d = -0.28), QOL (d = 0.48), social support (d = 0.36), and self-efficacy (d = 0.46). STEPP exceeds feasibility and acceptability thresholds, showing promising psychosocial benefits warranting a fully powered multisite efficacy trial. This trial was registered at www.clinicaltrials.gov as NCT06010017.
9 June 2026
Read appraisal →Bioorganic chemistry
In silico discovery and biological evaluation of a novel selective HDAC8 inhibitor featuring 1H-pyrazolo[3,4-b]pyridine scaffold
Histone deacetylase 8 (HDAC8), a pivotal epigenetic regulator orchestrating chromatin remodeling and transcriptional control, has emerged as a compelling anticancer target owing to its frequent dysregulation in malignancies. The development of isoform-selective inhibitors, however, confronts substantial challenges because of the pronounced structural conservation across HDAC isoforms. This study developed a high-efficiency drug screening pipeline primarily leveraging artificial learning (AI) models and molecular simulation techniques, and further evaluated the biological activity of computationally prioritized compounds through enzymatic inhibition assays and cellular experiments. The structurally novel compound Cmpd.16 was successfully identified, exhibiting promising inhibitory activity against HDAC8 (IC50 = 0.16 ± 0.01 μM) and moderately inhibited HCT116 cell proliferation mainly through the induction of apoptosis and G2/M phase cell cycle arrest. Subsequently, molecular dynamics simulations were employed to investigate the binding conformation of Cmpd.16 within the active pocket, and the key residues identified through free energy decomposition further elucidated the drug-target binding mode. Collectively, Cmpd.16, featuring 1H-pyrazolo[3,4-b]pyridine scaffold, was discovered via an efficient screening workflow, offering valuable insights to guide the rational design of HDAC8-targeted agents.
7 June 2026
Read appraisal →Acta microbiologica et immunologica Hungarica
Characteristics of fungaemia caused by Trichosporon species in South-Eastern Europe
The incidence of fungaemia caused by rare yeasts, particularly Trichosporon species, is rising globally, posing diagnostic and therapeutic challenges-especially in immunocompromised patients. This systematic review aims to analyse the epidemiology, diagnostic approaches, antifungal susceptibility, and clinical outcomes of Trichosporon fungaemia (TF) in South-Eastern Europe, including Turkey. A comprehensive search was conducted in PubMed and Scopus in August 2025. A total of 59 cases from 12 studies were identified, with Trichosporon asahii being the most prevalent species (86.4%). Cases originated from Turkey (79.7%), Greece (18.6%), and Croatia (1.7%). Diagnostic techniques varied, with phenotypic methods still widely used. MALDI-TOF MS and DNA sequencing were mainly applied as confirmatory methods. Haematologic disorders were the most frequently reported underlying conditions among the patients. Sixteen breakthrough fungaemia cases-occurring despite empirical or prophylactic antifungal therapy-were identified. Although rare, TF represents a severe infection with significant mortality in South-Eastern Europe. Early and accurate species identification-facilitated by advanced diagnostic tools-is crucial for effective management. In addition to diagnostic difficulties, treatment is also challenging. Voriconazole appears to be the preferred antifungal agent, even in breakthrough fungaemia cases. Enhanced awareness, routine use of molecular diagnostics, and ongoing epidemiological monitoring are essential to improve patient outcomes.
1 June 2026
Read appraisal →Science translational medicine
Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma
Traditional manufacturing of B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cell therapies is prolonged, leading to reduced patient access, T cell exhaustion, and consequently limiting therapeutic efficacy. To address this issue, we developed durcabtagene autoleucel, a BCMA-directed CAR T cell therapy manufactured using a rapid platform aimed at preserving T cell stemness. Here, we present the primary findings of part A of a phase 1 study (NCT04318327) of durcabtagene autoleucel in patients with relapsed/refractory multiple myeloma (r/r MM). The primary objective was safety; secondary objectives included response rates, cellular kinetics, immunogenicity, and manufacturing feasibility. Durcabtagene autoleucel was successfully manufactured for all 55 patients (median vein-to-vein time, 24 days) and given as a single infusion at one of four flat target doses (2.5 × 106 to 20 × 106 CAR T cells). Among all patients, the overall response rate was 98%, and the stringent complete response rate was 55%. Eighty percent of evaluable patients (35 of 44) achieved minimal residual disease negativity. There were no unexpected safety findings and no reports of delayed neurotoxicity. Immunophenotyping and transcriptomic analyses confirmed preservation of a stem-like phenotype in the manufactured final product. On the basis of the safety, efficacy, and cellular expansion results from the phase 1 trial, a phase 2 trial (NCT05172596) was initiated to further explore the efficacy and safety of durcabtagene autoleucel in heavily pretreated patients with aggressive r/r MM.
30 May 2026
Read appraisal →BMC nephrology
Roxadustat for CKD-related anemia in patients undergoing peritoneal dialysis: a systematic review and meta-analysis
BACKGROUND: CKD-related anemia remains a major complication in patients receiving peritoneal dialysis (PD), with limited treatment options beyond erythropoiesis-stimulating agents. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, has shown promise in correcting CKD-related anemia and modulating iron and metabolic parameters. However, its evidence in PD remains limited. METHODS: We conducted a systematic search of PubMed, Scopus, and Web of Science from inception to July 20, 2025. We included studies reporting the efficacy and safety of roxadustat in PD. Statistical analysis was performed using Review Manager (RevMan 5.4 for Windows) and R Studio. RESULTS: Eight studies were included in the meta-analysis (n = 607). Roxadustat significantly increased hemoglobin at all time points (MD 0.35 g/dL, 95% CI 0.28-0.41; p < 0.00001), serum iron (MD 0.95 µmol/L, 95% CI 0.02-1.89; p = 0.05), and total iron-binding capacity (MD 6.25 µmol/L, 95% CI 3.95-8.55; p < 0.00001), and reduced hepcidin (MD - 12.28 ng/mL, 95% CI - 21.06 to - 3.50; p = 0.006). No significant effects were observed for ferritin (p = 0.49), transferrin saturation (p = 0.45), cholesterol (p = 0.07), LDL (p = 0.14), HDL (p = 0.27), triglycerides (p = 0.26), CRP (p = 0.75), systolic blood pressure (p = 0.10), or diastolic blood pressure (p = 0.08). Heterogeneity was low to moderate for most outcomes. CONCLUSION: Roxadustat is effective in improving hemoglobin and iron metabolism in patients with PD, while exerting neutral effects on lipids, inflammation, and blood pressure. These findings support its role as a promising therapy for CKD-related anemia in PD. CLINICAL TRIAL NUMBER: Not applicable.
28 May 2026
Read appraisal →Clinical and experimental dermatology
An open-label phase II study of bitopertin in adults and adolescents with erythropoietic protoporphyria or X-linked protoporphyria
BACKGROUND: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare genetic disorders characterized by accumulation of protoporphyrin IX (PPIX), painful phototoxic reactions and hepatobiliary disease. No disease-modifying therapies are approved for these conditions. OBJECTIVES: To evaluate the safety and efficacy of bitopertin in adults and adolescents with EPP or XLP. METHODS: BEACON (ACTRN12622000799752) was a phase II, randomized, open-label, parallel-arm study in adult and adolescent participants with EPP or XLP. Participants received an oral, once-daily administration of bitopertin 20 mg or 60 mg for 24 weeks. RESULTS: Twenty-six participants were randomized to 20 mg (n = 14) or 60 mg (n = 12) of bitopertin. The study met its primary efficacy endpoint. Treatment with bitopertin resulted in significant, dose-dependent reductions in PPIX levels compared with baseline at both the 20-mg and 60-mg dose levels (mean -31.7%, SE 7.0; P < 0.001 vs. baseline and mean -57.7%, SE 7.4; P < 0.001 vs. baseline, respectively). Similar efficacy was observed across the adult and adolescent populations. No serious adverse events were reported. Dizziness was the most common adverse event reported with bitopertin, in 9 (64%) and 8 (67%) participants completing the study in the 20-mg and 60-mg dose groups, respectively. CONCLUSIONS: By reducing whole-blood PPIX levels, bitopertin targets the underlying pathophysiology of EPP, resulting in consistent improvements in multiple measures of light tolerance and quality of life. Bitopertin was well tolerated, and most adverse events were mild or moderate in severity.
27 May 2026
Read appraisal →Clinical chemistry and laboratory medicine
T-cell receptor beta constant 1 flow cytometry for diagnosing clonality in mature T-cell neoplasms: a systematic review and meta-analysis of diagnostic accuracy
INTRODUCTION: Accurate assessment of T-cell clonality is key for diagnosing mature T-cell neoplasms. TRBC1-based flow cytometry provides a rapid, robust, and cost-efficient approach. This systematic review and meta-analysis assessed the diagnostic accuracy of TRBC1 flow cytometry (TRBC1-FC) for detecting T-cell clonality in mature T-cell neoplasms. CONTENT: We systematically searched Scopus, PubMed (MEDLINE), and Google Scholar for articles on TRBC1-FC diagnostic accuracy published up to July 1, 2025. Pooled sensitivity and specificity were estimated, between-study heterogeneity was evaluated and small-study effects were examined. SUMMARY: This meta-analysis included 10 studies. The pooled sensitivity was 97.6 % (95 % CI, 95.1-99.4 %) and specificity 90.7 % (95 % CI, 76.0-99.3 %). The pooled LR+ was 10.9 (95 % CI, 4.1-28.9), LR-was 0.053 (95 % CI, 0.025-0.12), and DOR 339 (95 % CI, 64-1,788). The HSROC curve demonstrated an AUC of 0.974 (partial AUC=0.970), confirming excellent global discriminatory capacity. Between-study heterogeneity was substantial (I2=83.3 %), mainly affecting specificity and DOR, while sensitivity remained highly consistent. No evidence of a threshold effect was found. Deeks' test showed significant small-study effects (p<0.001), and sensitivity analyses identified one influential study whose exclusion markedly reduced heterogeneity. These results confirm the high diagnostic performance and robustness of TRBC1-FC for T-cell clonality assessment. OUTLOOK: TRBC1-FC demonstrates high sensitivity and low LR-, supporting its role as a rule-out test. Variability in specificity, LR+ and DOR, mainly due to small-study effects, advises caution for rule-in use. Standardized protocols and cost-effectiveness analyses are needed before broad clinical adoption.
26 May 2026
Read appraisal →Blood advances
Pediatric-inspired regimens and HSCT for adolescents and young adults with acute lymphoblastic leukemia
The best frontline treatment for acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs) is unclear. To support a clinical practice guideline, we systematically reviewed and meta-analyzed evidence on (1) asparaginase-based (pediatric) vs non-asparaginase-based (adult) regimens and (2) allogeneic hematopoietic stem cell transplantation (HSCT) vs no HSCT for AYAs (aged 15-39 years) with ALL in first complete remission. Data sources were PubMed, CINAHL, and PsycINFO from inception to 29 November 2023. Eligible studies compared regimens or the use of HSCT and reported survival, remission, toxicity, or quality of life in AYAs. We included 19 studies (14 comparative, 5 single-group; N = 3607) comparing regimens and 7 studies (N = 7492) comparing HSCT and no HSCT. Studies were mostly of poor quality, with sparse randomized controlled trials (RCTs), yielding low-certainty findings. Pediatric regimens were associated with higher 5-year overall survival (OS; relative risk [RR], 1.40; 95% confidence interval [CI], 1.18-1.65), event-free survival (RR, 1.80; 95% CI, 1.13-2.85), disease-free survival (DFS; RR, 1.55; 95% CI, 1.32-1.82), and lower treatment-related mortality (TRM; RR, 0.29; 95% CI, 0.09-0.90). HSCT was associated with lower 5-year OS (RR, 0.72; 95% CI, 0.61-0.84) and DFS (RR, 0.78; 95% CI, 0.68-0.90) and higher nonrelapse mortality (RR, 2.70; 95% CI, 1.18-6.18) and TRM (hazard ratio, 6.88; 95% CI, 3.02-15.70). Relapse risk varied by time point. In AYAs with Philadelphia chromosome-negative ALL, pediatric regimens may improve survival; toxicity-related evidence remains limited. HSCT may lead to inferior OS and DFS. With a dearth of RCTs, low-certainty evidence highlights the need for high-quality studies and subanalyses of AYAs.
26 May 2026
Read appraisal →Blood advances
A phase 1 trial of romidepsin, azacitidine, dexamethasone, and lenalidomide in relapsed or refractory T-cell lymphoma
Targeted therapies can induce responses in patients with relapsed/refractory T-cell lymphoma (R/R TCL) but are not curative. Genetic mutations associated with epigenetic and transcriptional dysregulation are common in many TCL subtypes, and drugs that modulate the epigenome and that target transcriptional regulators have synergistic activity in TCL. We hypothesized that fixed duration treatment with multiagent combinations of these drugs could produce deep responses leading to durable remissions. In a phase 1 trial, we tested escalating doses of lenalidomide added to romidepsin, azacitidine, and dexamethasone (RAdR) for patients with R/R TCL. The primary objective was to identify the maximum tolerated dose (MTD) of lenalidomide that could safely be used in RAdR. Secondary end points included response rate, survival, and markers of immune activation. Twenty-six patients enrolled and 21 were evaluable for response. Adverse events were predominantly gastrointestinal and hematologic. Grade 3/4 thrombocytopenia and neutropenia occurred in 19% and 21% of cycles, respectively. The MTD of lenalidomide was 20 mg. Among 9 patients treated at the MTD the objective response rate was 89% and complete response rate 22%. At 1 year, the estimated rate of progression-free survival was 14% and overall survival was 66%. Cell line models of anaplastic large cell lymphoma were interrogated to explore the activity of drug combinations in responding genetic subtypes. RAdR demonstrated activity in patients with highly refractory TCL but did not induce durable responses. This novel combination effectively bridged some patients with refractory TCL to consolidation such as allogeneic transplantation. This trial was registered at www.ClinicalTrials.gov as NCT04447027.
26 May 2026
Read appraisal →Blood advances
Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study
The phase 1 portion of SENTRY/XPORT-MF-034 (NCT04562389) evaluated the exportin 1 inhibitor selinexor (40 mg/60 mg once weekly) plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (n = 24). Primary end points were maximum tolerated selinexor dose, recommended clinical trial dose, and safety. No dose-limiting toxicities were reported. Common adverse events were nausea, fatigue, anemia, thrombocytopenia, constipation, vomiting, and headache. Nausea was transient, mainly grade 1, and managed by prophylactic antiemetics. Four deaths occurred, all unrelated to study treatment. Selinexor 60 mg in combination with ruxolitinib was identified as the recommended phase 3 dose based on safety, efficacy, and exposure-response analyses. Overall safety profiles and grades of clinically significant adverse events were similar and generally manageable regardless of selinexor dose. A greater proportion of patients achieved spleen volume reduction of ≥35% (SVR35) and total symptom score reduction of ≥50% (TSS50) at week 24 in the selinexor 60-mg group (79% and 58%) than the 40-mg group (38% and 25%). Among evaluable patients who received suboptimal ruxolitinib ≤5 mg twice daily in the selinexor 60-mg group, SVR35 was observed in 100% (6/6) and TSS50 in 75% (3/4) of patients. The trial was registered at ClinicalTrials.gov as NCT04562389.
26 May 2026
Read appraisal →Blood advances
Phase 2 study of the lysine-specific demethylase 1 inhibitor bomedemstat for essential thrombocythemia
Novel treatments that can improve outcomes of essential thrombocythemia (ET) are needed. In a phase 2 trial, participants with ET who required cytoreduction and had inadequate response to, or were intolerant of, ≥1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200 × 109/L to 400 × 109/L). Primary end points were safety and response, defined as a platelet count of ≤400 × 109/L without new thromboembolic events. Of 73 who received bomedemstat, at 24 weeks, 49 of 64 evaluable participants (77%) achieved a response. Durable reductions in platelet count (≤400 × 109/L for ≥12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10 × 109/L for ≥12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10 × 109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ≥1 thrombotic event, and 15 of 73 (21%) experienced ≥1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. This trial was registered at www.clinicaltrials.gov as #NCT04254978.
26 May 2026
Read appraisal →Neurosurgical review
The role of preoperative thrombocytic factors on survival in patients with glioblastoma: a meta-analysis and synopsis of the literature
Glioblastoma (GBM) is the most common malignant primary brain tumour and is associated with poor prognosis. Platelet-related factors have been linked to outcomes in GBM, but evidence remains inconsistent. This review evaluates their prognostic value for survival. We conducted a systematic review and meta-analysis of studies on preoperative thrombocytic factors in GBM. PubMed, MEDLINE, and Embase were searched from inception to January 2025 using MeSH terms. Eligible studies included observational cohort studies of adults (≥ 16 years) with WHO grade 4 diffuse astrocytoma (GBM), ≥ 30 participants, and ≥ 3 months' follow-up after resection. Random-effects meta-analysis using restricted maximum likelihood with Hartung-Knapp adjustment was used to pool hazard ratios (HRs) of high vs. low parameters on overall survival (OS). Study quality was assessed with the Newcastle-Ottawa Scale. 21 studies were included. 13 (n = 2609) reported HRs of high vs. low platelet: lymphocyte ratio (PLR, median threshold = 150), with high PLR significantly associated with worse OS (pooled HR = 1.46, 95% CI [1.23, 1.74]). Eight studies (n = 1921) assessed platelet count (PC, median threshold = 208*109/L), showing high PC was a borderline predictor of worse OS (pooled HR = 1.38, 95% CI [1.00, 1.90]). Four studies (n = 1234) examined mean platelet volume (MPV, median cut-off = 9.05 fL), which qualitatively demonstrated worse OS in patients with high MPV or high MPV: PC ratio. One study assessed platelet distribution width (PDW, threshold = 14.7 fL), finding worse OS in the high PDW group. High preoperative PLR is associated with poor prognosis in GBM, while high PC demonstrates borderline increased risk, which may help refine risk stratification and guide future mechanistic studies.
25 May 2026
Read appraisal →Annals of medicine
Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis
BACKGROUND: No systematic review has evaluated the existing evidence regarding the association between packed red blood cell (pRBC) transfusion and clinical worsening of necrotizing enterocolitis (NEC) in neonates. This systematic review and meta-analysis was conducted to address this knowledge gap. MATERIALS AND METHODS: We searched the Cochrane Library, EBSCO, Embase, Web of Science, Google Scholar, and PubMed for studies on pRBC transfusion and NEC published before May 10, 2025. Relevant articles were selected through title, abstract, and full-text screening. English-language case-control studies or cohort studies, or randomized controlled trials involving newborns with NEC that compared pRBC transfusion with no transfusion and reported changes in NEC clinical status were included. Review articles, systematic reviews, case reports, editorials, animal studies, duplicate publications, and studies with incomplete data were excluded. RESULTS: Five studies involving 971 neonates with NEC were included. The pooled analysis demonstrated a potential association between pRBC transfusion and clinical deterioration of NEC in neonates (odds ratio: 6.05, 95% confidence interval: 3.02-12.14). CONCLUSIONS: pRBC transfusion was associated with an exacerbation of NEC in neonates. However, these findings should be interpreted cautiously because of the small number of eligible studies included in this meta-analysis, and future large-scale, well-designed studies are needed to confirm the observed association. Published studies have identified an association between pRBC transfusion and NEC progression; however, whether this association is causal remains unclear.Despite consistent evidence from observational studies suggesting a potential association between pRBC transfusion and NEC progression, the overall quality of the evidence is low because of the lack of randomized controlled trials to determine causality.
25 May 2026
Read appraisal →Occupational and environmental medicine
Lymphoid neoplasms and benzene exposure using a revised classification scheme: systematic review and meta-analysis
Lymphoid neoplasms are a diverse group of cancers derived from lymphocytes, with classification recently updated by the 5th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5). Benzene, a well-known carcinogen, is widely used in industries and environmental exposures vary; however, its association with specific lymphoid neoplasm subtypes remains unclear due to historical classification challenges. This study aimed to clarify the risk of lymphoid neoplasms related to benzene exposure using the updated WHO-HAEM5 framework.A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies were comparative human studies evaluating benzene exposure and lymphoid neoplasm risk, with sufficient data for risk estimates. Inclusion criteria specified study designs, participants, exposures and outcomes based on clinical diagnoses. Data were independently extracted by multiple reviewers. The main outcome was risk of lymphoid neoplasms and subtypes analysed by random-effects meta-analysis with heterogeneity and bias assessments.From 1488 records, 95 studies met criteria (65 occupational and 30 environmental exposure). Benzene exposure significantly increased overall lymphoid neoplasm risk (RR 1.26; 95% CI 1.18 to 1.35). B-cell neoplasms showed elevated risk (RR 1.26; 95% CI 1.16 to 1.37), including mature B-cell neoplasms, Hodgkin lymphoma and plasma cell neoplasms. T-cell and natural killer cell neoplasm risk was not significantly increased overall. Occupational exposures conferred higher risks with lower heterogeneity than environmental exposures.Benzene exposure is strongly associated with increased risk of lymphoid neoplasms, particularly B-cell subtypes, supported by the refined WHO-HAEM5 classification reducing heterogeneity. This study underscores the importance of biologically informed disease classification and the need for targeted occupational safety and environmental health policies.The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration ID: CRD420251063844) .
23 May 2026
Read appraisal →Postgraduate medical journal
Next-generation cancer therapies: translating experimental advances into clinical practice
Recent advancements in cancer therapy have led to the emergence of innovative approaches that offer new hope to patients. This review provides a comprehensive overview of the latest cutting-edge technologies and strategies in cancer treatment, including clinically approved therapies and experimental modalities in preclinical or early clinical development, with a focus on their potential to improve patient outcomes. We examined next-generation therapies, including personalized immunotherapies, targeted molecular treatments, gene editing approaches, and artificial intelligence-driven strategies. By evaluating the current landscape of these therapies, we highlighted their benefits, limitations, and future directions. The integration of these advanced modalities into clinical practice holds promise for enhancing their efficacy, reducing side effects, and ultimately transforming cancer care.
22 May 2026
Read appraisal →European heart journal. Acute cardiovascular care
Guided de-escalation of antiplatelet treatment in patients at high atherothrombotic risk presenting with acute coronary syndrome: a post hoc analysis of the TROPICAL-ACS trial
AIMS: Platelet function testing (PFT)-guided de-escalation of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been shown to reduce bleeding risk without increasing ischaemic events. Patients with high atherothrombotic risk (ATR) remain a challenging subgroup for such strategies. This study evaluated the safety and efficacy of early PFT-guided DAPT de-escalation according to ATR status. METHODS AND RESULTS: In the TROPICAL-ACS trial, 2610 ACS patients were randomized to standard 12-month prasugrel therapy or PFT-guided DAPT de-escalation. For this post hoc analysis, patients were stratified by ATR. High ATR was defined as age ≥ 65 years, polyvascular disease, or ≥2 risk factors (diabetes, smoking, or renal dysfunction). Hazard ratios (HRs) for clinical endpoints were derived using multistate Cox regression. High-ATR patients (n = 990) had a higher incidence of the primary net clinical benefit endpoint-composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium 2-5 bleeding-compared with low-ATR patients (n = 1620) (11.0% vs. 6.7%; HR 1.67, 95% confidence interval 1.28-2.18; P < 0.001). Platelet function testing-guided de-escalation showed no significant interaction by ATR status for the primary endpoint [high ATR: 10.5% vs. 11.5%, HR 0.90 (0.61-1.32), P = 0.586; low ATR: 5.6% vs. 7.7%, HR 0.71 (0.48-1.04), P = 0.082; Pinteraction = 0.394] or ischaemic events [high ATR: 3.7% vs. 4.4%, HR 0.83 (0.44-1.56); low ATR: 1.8% vs. 2.6%, HR 0.68 (0.35-1.34); Pinteraction = 0.666]. CONCLUSION: Early PFT-guided de-escalation from prasugrel to clopidogrel was safe across atherothrombotic risk categories, supporting individualized DAPT optimization in ACS patients with both low and high ischaemic risk.
21 May 2026
Read appraisal →Biomedical microdevices
Automated blood group classification using a digital microfluidics chip and vision transformer-based image analysis
Identifying blood groups accurately is critical for safe medical practices, especially in emergencies, surgeries, and prenatal care. Conventional methods often depend on visual inspection of agglutination reactions, which can be error-prone, particularly when using small sample volumes. In this work, we introduce an efficient and intelligent system for blood type detection that combines digital microfluidics with advanced deep learning and antigen-based decision logic. A Vision Transformer (ViT) model was trained to recognize agglutination patterns in droplet-based blood images, followed by an automated mapping of standard ABO/Rh rules to assign the corresponding blood group based on antigen presence. The proposed system achieved 100% accuracy specifically in detecting antigen-antibody agglutination reactions, with perfect scores across precision, recall, specificity, and F1-score. Our method reduces the need for large reagent volumes and minimizes testing cost, while also improving reliability. In future work, our aim is to embed this system into a compact, microfluidics paper-based device, enabling low-cost, AI-assisted blood typing in portable point of care settings.
21 May 2026
Read appraisal →Revista do Instituto de Medicina Tropical de Sao Paulo
Molecular biomarkers associated with ATLL and HAM progression in HTLV-1 infection: a systematic review
Human T-lymphotropic virus type 1 (HTLV-1) infects approximately five to 10 million individuals worldwide, although only a minority develop severe outcomes such as adult T-cell leukemia/lymphoma (ATLL) or HTLV-1-associated myelopathy (HAM). Proviral load (PVL), while widely used, shows limited sensitivity and specificity, reinforcing the need for complementary biomarkers. Omics-based approaches have emerged as promising tools to improve risk prediction. We conducted a systematic review following PRISMA guidelines, searching PubMed, Web of Science, Virtual Health Library (BVS), and CAPES Periodicals databases for studies published between May 2020 and May 2025. Eligible studies included original observational designs investigating genomic, proteomic, and metabolic biomarkers associated with progression to ATLL or HAM. Methodological quality was assessed using tools from the National Heart, Lung, and Blood Institute (NHLBI). In total, 35 studies met the inclusion criteria, most conducted in Brazil, Japan, and Iran. A total of 67 biomarkers were identified: 37 genomic, 27 proteomic, and three metabolic with potential clinical applications in risk stratification, prognosis, and therapeutic monitoring of HTLV-1 infection. PVL remained the most frequently investigated marker but lacked predictive power in isolation. Additional candidates with strong potential included IFN-γ, CXCL10, Neopterin, AnxA1, and sTNFR2. This review highlights the potential of integrated multiparametric panels-combining PVL with omics-derived biomarkers-as a promising strategy to improve risk stratification, prognosis, and therapeutic monitoring in people living with HTLV-1 (PLHTLV-1). However, further longitudinal and clinically validated studies are needed to confirm their applicability and support their translation into early intervention strategies, particularly during the asymptomatic phase.
20 May 2026
Read appraisal →Journal of the American Heart Association
Association of Edoxaban Pharmacokinetics With Bleeding in Older Patients With Atrial Fibrillation Treated With Low-Dose Edoxaban: A Post Hoc Analysis of a Randomized Controlled Trial
BACKGROUND: Edoxaban is a direct oral anticoagulant used for stroke prevention in patients with atrial fibrillation (AF) and treatment of venous thromboembolism. We examined the relationship between trough edoxaban concentrations (E-trough) and prothrombin time (PT) and major bleeding in very old Japanese patients with atrial fibrillation and high bleeding risk. METHODS: In this post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled ELDERCARE-AF (Study of DU-176b Aged 80 Years or Older) trial, patients were randomly assigned 1:1 to edoxaban 15 mg or placebo once daily. After 8 weeks of treatment, E-trough was determined and the incidence of major bleeding examined in each quartile. The incidence of major bleeding by PT was also examined. RESULTS: Data were obtained from 427 patients. E-trough (ng/mL) was ≤9.24 in the first quartile (107 patients), >9.24 to ≤13.6 in the second (111 patients), >13.6 to ≤21.6 in the third (103 patients), and >21.6 in the fourth (106 patients). Older age, lower body weight, lower creatinine clearance, and the presence of congestive heart failure were independent predictors of higher E-trough. Higher E-trough was associated with greater incidence of major bleeding (0.8%, 1.9%, 3.4%, and 4.7%/year, respectively, P=0.0408). There was a significant positive correlation between E-trough and PT (r=0.426, P<0.0001). Significantly more major bleeding events occurred in the longer (>13 seconds) versus shorter (≤13 seconds) PT subgroups (4.61% versus 0.98%/year, P=0.0060). CONCLUSIONS: Several factors were associated with higher E-trough and increased risk of major bleeding events. PT >13 seconds may be a useful predictor of the development of major bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02801669.
20 May 2026
Read appraisal →JAMA
Tucidinostat Plus R-CHOP vs R-CHOP in MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma: A Randomized Clinical Trial
IMPORTANCE: Epigenetic dysregulation is associated with the pathogenesis and progression of diffuse large B-cell lymphoma (DLBCL). MYC/BCL2 double-expressor lymphoma (DEL), a distinct population of DLBCL defined by MYC and BCL2 coexpression, refers to poor prognosis after standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy. Tucidinostat (or chidamide), an oral, selective histone deacetylase inhibitor, has shown promising activity in DEL. OBJECTIVE: To evaluate efficacy and safety of tucidinostat plus R-CHOP vs R-CHOP alone as first-line treatment for patients with DEL. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled phase 3 trial enrolled patients from May 21, 2020, through July 25, 2022, with follow-up to June 26, 2025. The trial was conducted at 40 study centers in China; a total of 423 eligible patients were enrolled. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to receive oral tucidinostat (20 mg on days 1, 4, 8, and 11 of each 21-day cycle) or matching placebo, plus 6 cycles of R-CHOP. Patients with a complete response after combination therapy received either tucidinostat or placebo maintenance up to 24 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was event-free survival. Secondary end points included complete response rate, progression-free survival, disease-free survival, overall survival, and tolerability. RESULTS: Among 423 patients randomized (median age, 63 years; 47.5% male), the median follow-up duration from randomization was 41.3 months. The tucidinostat group demonstrated a 28% lower risk of disease progression, relapse after complete response, death, or initiation of new therapy for residual disease compared with the placebo group (stratified hazard ratio, 0.72 [95% CI, 0.54-0.96]; P = .02), with a 2-year event-free survival rate of 60.3% vs 50.5%, respectively. The complete response rate was 73.0% vs 61.8% (difference, 11.1% [95% CI, 2.3%-20.0%]), respectively. Increased toxicity associated with treatment was observed in the tucidinostat group but generally manageable with supportive care. CONCLUSIONS AND RELEVANCE: Tucidinostat plus R-CHOP significantly improved event-free survival, with manageable toxicity in patients newly diagnosed with DEL. This trial is the first to demonstrate the benefit of an epigenetic modulator in DLBCL, offering a new first-line therapeutic approach dually targeting MYC and BCL2 oncoprotein for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04231448.
20 May 2026
Read appraisal →Journal for immunotherapy of cancer
Clinical outcomes and spatial transcriptomic profiles of CD19/20 CAR-T therapy in relapsed or refractory B-cell non-Hodgkin's lymphoma
BACKGROUND: Relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma (B-NHL) remains a major therapeutic challenge despite CD19-directed chimeric antigen receptor (CAR) T-cell therapies, with treatment failure often driven by antigen escape and limited CAR-T persistence. Dual targeting of CD19 and CD20 may mitigate antigen loss. We conducted an expanded phase I/II study of bispecific CD19/20 CAR-T cells and incorporated spatially resolved single-cell transcriptomics to evaluate tumor-intrinsic and microenvironmental factors of clinical response. METHODS: Patients with R/R B-NHL received CD19/20 CAR-T cells following lymphodepletion. Efficacy, safety, CAR-T expansion/persistence, and B-cell reconstitution were assessed. Pretreatment tumor biopsies from five patients with divergent outcomes underwent spatial single-cell transcriptomic profiling. RESULTS: 32 patients were treated, including 24 with diffuse large B-cell lymphoma. Among 31 evaluable patients, the best overall response rate was 74%, including 58% achieving complete remission. Median progression-free and overall survival were 6.8 and 22.1 months, respectively. Response rates were higher in patients with normal lactate dehydrogenase. CAR-T expansion peaked on days 7-17, and persistence exceeded 500 days in long-term responders. Cytokine release syndrome occurred in 53% (12% grade ≥3) and immune effector cell-associated neurotoxicity syndrome in 9% (all grade 3), with no lasting deficits. Spatial profiling identified two dominant tumor architectures: (1) a B-cell-dominant phenotype, in which durable remission was associated with heightened apoptotic competence in malignant B cells, and (2) a fibroblast-enriched and monocyte/macrophage-enriched phenotype, in which response correlated with a chemokine-rich, T-cell-permissive microenvironment. CONCLUSIONS: Bispecific CD19/20 CAR-T therapy produced durable clinical activity with manageable toxicity. Spatial single-cell analysis reveals distinct tumor-intrinsic and microenvironmental features associated with CAR-T responsiveness, providing a spatially informed framework for understanding heterogeneous therapeutic outcomes. TRIAL REGISTRATION NUMBER: NCT04723914.
18 May 2026
Read appraisal →Lancet (London, England)
Addition of autologous stem-cell transplantation to an ibrutinib-containing first-line treatment in patients aged 18-65 years with mantle cell lymphoma (TRIANGLE): 4·5-year follow-up of a three-arm, randomised, open-label, phase 3 superiority trial of the European MCL Network
BACKGROUND: Adding ibrutinib to standard, first-line immunochemotherapy improves failure-free survival in adult patients aged 18-65 years with mantle cell lymphoma, according to the first results from the TRIANGLE trial. With prolonged follow-up, we investigated whether the addition of autologous stem-cell transplantation (ASCT) to an ibrutinib-containing regimen improves failure-free survival, and evaluated effects on overall survival. METHODS: We conducted a three-arm, randomised, open-label, phase 3 superiority trial (TRIANGLE) in 165 secondary or tertiary clinical centres, with experience in mantle cell lymphoma treatment and the capability to perform ASCT or an association with such a centre, in 13 European countries and Israel. Patients aged 18-65 years with untreated, stage II-IV mantle cell lymphoma and suitable for ASCT were randomly assigned (1:1:1) to control group A or experimental groups A + I or I. Randomisation was done using computer-generated random numbers and stratified by study groups and Mantle Cell Lymphoma International Prognostic Index risk groups. Treatment in group A consisted of six alternating, 21-day cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, cyclophosphamide 750 mg/m2 on day 1, doxorubicin 50 mg/m2 on day 1, vincristine 1·4 mg/m2 on day 1 [up to a maximum of 2 mg], and oral prednisone 100 mg on days 1-5) and R-DHAP or R-DHAOx (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, high-dose intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, plus either intravenous cisplatin 100 mg/m2 over 24 h on day 1 [R-DHAP] or intravenous oxaliplatin 130 mg/m2 on day 1 [R-DHAOx]), followed by ASCT. In group A + I, oral ibrutinib (560 mg daily) was added on days 1-19 of R-CHOP cycles and as 2-year maintenance after ASCT. In group I, ibrutinib was given the same way, but ASCT was omitted. Rituximab maintenance was allowed in all treatment groups according to national guidelines. Three pairwise, one-sided, log-rank tests for the primary outcome (failure-free survival) were statistically monitored. The primary analysis was by intention to treat and included all randomly assigned patients, ignoring protocol deviations. Safety was assessed in randomly assigned patients who started any trial treatment component of the respective treatment phase. The trial is registered with ClinicalTrials.gov (NCT02858258) and is complete. FINDINGS: Between July 29, 2016, and Dec 28, 2020, 870 patients (662 [76%] were male, 208 [24%] were female) were randomly assigned to group A (n=288), group A + I (n=292), or group I (n=290). After median follow-up of 54·9 months (95% CI 54·4-56·0), group A + I did not show superiority over group I, with 4-year failure-free survival of 82% (95% CI 78-87) versus 81% (76-86; hazard ratio [HR] 0·86 [one-sided 98·33% CI 0·00-1·27]; one-sided p=0·21). Group A + I remained superior to group A (82% [78-87] vs 70% [65-76]; HR 0·63 [one-sided 98·33% CI 0·00-0·89]; one-sided p=0·0026) and, as before, group A did not show superiority over group I (70% [65-76] vs 81% [76-86]; HR 1·45 [one-sided 98·33% CI 0·00-2·02]; one-sided p=0·99). 4-year overall survival was 88% (95% CI 84-92) in group A + I versus 81% (76-85) in group A (HR 0·59 [95% CI 0·38-0·92], p=0·0036) and 90% (87-94) in group I versus 81% (76-85) in group A (0·57 [0·36-0·90], p=0·0019). During maintenance or follow-up, the most common grade 3-5 adverse events were haematological disorders, reported in 127 (54%) of 234 patients in group A + I versus 74 (28%) of 269 in group I and 56 (23%) of 240 patients in group A, and infections, reported in 80 (34%) of 234 patients in group A + I versus 71 (26%) of 269 in group I and 37 (15%) of 240 patients in group A. Infections and infestations were the most common fatal adverse events during maintenance or follow-up, occurring in four (2%) of 234 patients in group A + I and five (2%) of 269 patients in group I. INTERPRETATION: After a prolonged follow-up of 55 months, both ibrutinib-containing groups showed relevant improvements not only in failure-free survival-a modified form of progression-free survival-but also in overall survival. In contrast, the addition of ASCT to an ibrutinib-containing regimen had no supplementary benefit but increased toxicity. Induction treatment with ibrutinib and R-CHOP plus R-DHAP (or R-DHAOx), followed by 2 years of maintenance treatment with ibrutinib, should be considered as a new standard of care for younger patients with mantle cell lymphoma. FUNDING: Janssen.
18 May 2026
Read appraisal →Clinica chimica acta; international journal of clinical chemistry
Exploring clinical feasibility of zero-shot learning in a large language model for immunofixation electrophoresis image interpretation
INTRODUCTION: Immunofixation electrophoresis (IFE) is the gold standard method for detecting and typing monoclonal immunoglobulins, but its interpretation requires expert evaluation and remains susceptible to subjectivity and variability. Recent advances in multimodal large language models (LLMs) have enabled zero-shot visual reasoning without task-specific training. This study aimed to evaluate the feasibility and diagnostic performance of zero-shot multimodal LLMs for automated interpretation of IFE images. MATERIALS AND METHODS: A dataset of 487 immunofixation electrophoresis images representing ten semantic classes (AK, AL, GK, GL, K, L, LGL, MK, ML, and NONE) was retrospectively collected and annotated by expert laboratory specialists. Two multimodal LLMs, ChatGPT-5.2 and Gemini3 Pro, were evaluated using a zero-shot visual question answering (ZS-VQA) framework without additional training or fine-tuning. Each image was analyzed using two prompt configurations: a simple prompt and a detailed prompt with structured diagnostic guidance. Model performance was assessed using precision, recall, F1-score, and confusion matrix analysis. RESULTS: Gemini outperformed ChatGPT across most classes, particularly with detailed prompts, achieving high F1-scores in clinically relevant monoclonal categories such as MK (89.80), AK (84.75), and GK (71.54). Detailed prompting consistently improved recall and F1-scores, underscoring the importance of prompt design. In contrast, ChatGPT showed lower recall, F1-scores, and classification consistency. Both models performed less effectively in visually subtle patterns. CONCLUSIONS: Zero-shot multimodal LLMs, particularly Gemini, show promising potential for interpreting IFE images without task-specific training. However, performance variability and limitations in certain classes indicate that further optimization and validation are required before clinical implementation.
18 May 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
Allogeneic B7-H3-Targeted CAR Vδ1T-cell Therapy in Advanced Solid Tumors: A Phase I Study
PURPOSE: The aim of the study was to evaluate the safety, pharmacokinetics, and preliminary clinical activity of UTAA06, an "off-the-shelf" allogeneic B7-H3-targeted chimeric antigen receptor (CAR) Vδ1T-cell therapy, in patients with pretreated, advanced B7-H3-positive solid tumors. PATIENTS AND METHODS: In this first-in-human, phase I, dose-escalation study (NCT06372236), 10 patients with advanced solid tumors (including gastric, colorectal, hepatocellular, ovarian, and neuroendocrine cancers) were enrolled. Following lymphodepletion chemotherapy (cyclophosphamide and fludarabine), patients received UTAA06 infusion across three dose levels (5 × 108, 8 × 108, or 1 × 109 cells). The primary endpoint was safety. Secondary endpoints included pharmacokinetics and antitumor efficacy. RESULTS: UTAA06 demonstrated a manageable safety profile; no GVHD was observed, and cytokine release syndrome was limited to two transient grade 1 events. A single dose-limiting toxicity (grade 3 pneumonitis) was reported in one patient at the 5 × 108 cell dose level. Although UTAA06 demonstrated signals of biological activity, including transient reductions in serum tumor markers in 50% of patients, no objective response by RECIST v1.1 criteria was observed. Further analysis identified that the limited CAR T-cell persistence was likely driven by subclinical host-versus-graft rejection. CONCLUSIONS: This study provides clinical proof of concept for allogeneic B7-H3-targeted CAR-Vδ1T cells as a safe platform with low risk of GVHD and demonstrable biological activity in solid tumors. However, clinical efficacy was constrained by limited cellular persistence caused by host immune rejection. Future strategies are required to enhance the durability and therapeutic potential of this allogeneic approach.
17 May 2026
Read appraisal →Clinical cancer research : an official journal of the American Association for Cancer Research
Efficacy and Safety of Belantamab Mafodotin with Bortezomib plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: The DREAMM-6 Arm B Trial
PURPOSE: The phase I/II DREAMM-6 arm B study (NCT03544281) explored belantamab mafodotin combined with bortezomib/dexamethasone (BVd) in relapsed/refractory multiple myeloma (RRMM). PATIENTS AND METHODS: Adults with RRMM were enrolled sequentially in two belantamab mafodotin (intravenous) dose-escalation (DE) cohorts (2.5 then 3.4 mg/kg every 3 weeks). Additional patients enrolled sequentially to eight dose-expansion cohorts: 1.9, 2.5, or 3.4 mg/kg every 3 weeks; 2.5 or 3.4 mg/kg every 3 weeks split dose (days 1 and 8); 1.9 or 2.5 mg/kg every 6 weeks; or 2.5 mg/kg in cycle 1 stepped down to 1.9 mg/kg every 6 weeks thereafter. Patients received bortezomib twice weekly and dexamethasone four times weekly. Endpoints were dose-limiting toxicities (DLT; DE), adverse events (AE), serious AEs (SAE; DE and expansion), overall response rate (ORR; expansion), and pharmacokinetics. RESULTS: One hundred seven patients (median 4 prior lines of therapy) received BVd (n = 12-18/cohort). The median follow-up was 15.2 to 25.4 months. No DLTs occurred during DE. The most common grade 3/4 AE was keratopathy (53%). Protocol-defined ocular events (change in best corrected visual acuity and/or corneal examination findings) were reported in 93% of patients (grade 3/4: 77%). Twenty-eight (26%) patients experienced any study treatment-related SAEs; 3 of 7 fatal SAEs had a treatment-related primary cause. The ORR was 70% (95% confidence interval, 60.5-78.6). Higher initial exposures had higher probabilities of response and ocular events; lower exposures resulted in fewer deep responses, with small differences in ocular events. CONCLUSIONS: BVd demonstrated manageable safety and clinical activity across all dosing cohorts in heavily pretreated RRMM, supporting the 2.5 mg/kg every 3 weeks dose.
17 May 2026
Read appraisal →PloS one
D-dimer and lower limb ultrasound as prognostic factors for recurrent deep venous thrombosis and pulmonary embolism: A systematic review and meta-analysis
Venous thromboembolic disease is a chronic, recurrent condition. The optimal duration of anticoagulation therapy remains uncertain. We aim to evaluate D-dimer and lower limb ultrasonography as prognostic tools for the recurrence of venous thromboembolism. A search was conducted on May 28, 2022, in the Medline, Embase, and Cochrane databases. Inclusion criteria encompassed cohort studies, case-control studies, and clinical trials. Two reviewers independently screened all records and analyzed studies for inclusion/exclusion criteria, as well as risk of bias, using a structured framework (PROSPERO ID: CRD42022341082). The initial search yielded 4652 titles and abstracts. After removing 777 duplicates and reviewing 3875 titles and abstracts, 48 articles providing information on D-dimer and/or lower limb ultrasonography as prognostic factors were finally included. Very low-certainty evidence suggests that both residual vein thrombosis (RVT) at anticoagulation discontinuation and a positive post-treatment D-dimer are significantly associated with an increased risk of recurrent venous thromboembolism (VTE). For RVT, the pooled analysis showed a two-fold increase in risk (OR 2.00, 95% CI 1.02 to 3.94; I² = 85.7) while for positive D-dimer, the risk was similarly elevated (OR, 2.48; 95% CI, 1.85-3.33; I² = 56.0). In conclusion, very low-quality evidence suggests that abnormal D-dimer and RVT are associated with recurrent VTE; however, this association is inconsistent due to significant heterogeneity and wide prediction intervals. These biomarkers should be interpreted with caution as isolated predictors in clinical practice.
16 May 2026
Read appraisal →Blood
Evolution of tumor subclones and T-cell dynamics underlie variable ibrutinib responses in Waldenström macroglobulinemia
To elucidate the molecular basis underlying differential responses and resistance to ibrutinib in Waldenström macroglobulinemia (WM), we conducted a prospective phase 2 trial of ibrutinib monotherapy in treatment-naïve patients. A total of 74 sequential bone marrow (BM) aspirates from 17 patients, collected from baseline through 48 treatment cycles, were profiled using single-cell multiomics. BM cells were segregated primarily into B-cell/plasma cell and T-cell compartments. Longitudinal clonal tracking of malignant B cells/plasma cells identified 3 distinct evolutionary patterns: evolution (early clone contraction with late clone expansion and increasing genomic complexity), devolution (early clone expansion with late clone contraction and genomic simplification), and no evolution (stable clonal architecture). The evolution pattern was strongly associated with disease progression, whereas devolution correlated with durable clinical response. Transcriptomic profiling of resistant clones enabled development and validation of the Waldenström ibrutinib prediction (WIP) score, which predicted treatment response at baseline. Within the WIP signature, LYN emerged as a key regulator; LYN knockdown or inhibition significantly increased WM cell sensitivity to ibrutinib, suggesting a rational combination strategy. In parallel, GZMB+ CD8+ effector-memory T cells expanded after treatment in patients with progressive disease and coexisted with tumor evolution. These cells exhibited persistently impaired cytotoxic programs (eg, GNLY), a dedifferentiated memory-like state, elevated PDCD1 expression, and reduced T-cell receptor diversity. Together, this study provides, to our knowledge, the first single-cell framework of tumor clonal evolution and T-cell dysfunction under ibrutinib in WM, introduces the WIP score as a predictive biomarker for treatment response, and identifies actionable tumor-intrinsic and immune mechanisms driving resistance. This trial was registered at www.ClinicalTrials.gov as NCT02604511.
16 May 2026
Read appraisal →BMJ (Clinical research ed.)
Efficacy of dual antiplatelet therapy for three months versus 12 months after coronary artery bypass grafting: multicentre, double blinded, randomised controlled trial
OBJECTIVES: To evaluate the efficacy of dual antiplatelet therapy (DAPT) for three months versus 12 months in saphenous vein graft occlusion while reducing bleeding risk. DESIGN: Multicentre, non-inferiority, double blind, randomised controlled trial. SETTING: 13 cardiac surgery centres in China, with enrolment between February 2023 and July 2024. PARTICIPANTS: 2300 participants aged 18 to 80 years who underwent elective primary coronary artery bypass grafting with ≥1 saphenous vein graft. INTERVENTIONS: Participants were randomly assigned (1:1) to receive DAPT (ticagrelor 90 mg twice daily plus aspirin 100 mg once daily) for 12 months or the same dual antiplatelet regimen for the first three months, followed by placebo plus aspirin for nine months. MAIN OUTCOME MEASURES: The primary outcomes were saphenous vein graft occlusion at one year (non-inferiority) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (superiority). Secondary outcomes were major adverse cardiovascular events (MACCE), saphenous vein graft failure, venous or arterial graft stenosis, and venous or arterial graft occlusion. RESULTS: 2290 patients (mean age 61.5 (standard deviation (SD) 8.4) years, 20.6% (n=472) women) were included in the modified intention-to-treat set. The mean number of saphenous vein graft segments was 2.5 (SD 0.8). 2070 patients (90.4%) with a total of 5125 saphenous vein graft segments were assessed at one year. Saphenous vein graft occlusion occurred in 280 of 2596 (10.8%) in the three month DAPT group and 283 of 2529 (11.2%) in the 12 month DAPT group (absolute difference -0.31%, 95% confidence interval (CI) -3.13% to 2.52%; P=0.008 for non-inferiority). During a median follow-up of 368 (interquartile range 358-382) days, BARC type 2, 3, or 5 bleeding occurred in 95 patients (8.3%) in the three month DAPT group and 149 patients (13.2%) in the 12 month DAPT group (absolute difference -4.67%, 95% CI -7.18% to -2.16%; P<0.001). The number needed to treat to prevent one bleeding event was 21 (95% CI 13 to 46). MACCE occurred in 26 (2.3%) patients in the three month DAPT group and 27 (2.7%) in the 12 month DAPT group (absolute difference -0.11%, 95% CI -1.48% to 1.26%). The findings for other secondary outcomes were also similar between the two groups. CONCLUSIONS: A three month DAPT strategy was non-inferior to the 12 month DAPT strategy in saphenous vein graft occlusion and was superior in reducing bleeding risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT05380063.
15 May 2026
Read appraisal →Renal failure
Comparative efficacy and safety of apixaban and rivaroxaban versus warfarin in atrial fibrillation patients with end-stage renal disease: a systematic review and meta-analysis
This study aimed to evaluate the comparative efficacy and safety of apixaban and rivaroxaban versus vitamin K antagonists (VKAs) in anticoagulation management in a dialysis population. PubMed, Embase, and the Cochrane Library were searched for studies comparing apixaban or rivaroxaban with VKAs in patients with atrial fibrillation (AF) undergoing dialysis. The primary efficacy endpoints included stroke/systemic embolism (SSE) and all-cause mortality. Safety outcomes encompassed major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. Risk ratios (RR) with 95% confidence intervals (CI) were synthesized using random-effects models. The meta-analysis included three randomized controlled trials (RCTs) and eight observational studies. Pooled analyses showed that apixaban and rivaroxaban were associated with lower risks of major bleeding (RR 0.57, 95% CI: 0.51-0.63), gastrointestinal bleeding (RR 0.66, 95% CI: 0.57-0.76), and intracranial hemorrhage (RR 0.54, 95% CI: 0.36-0.83) compared with VKAs. Additionally, apixaban and rivaroxaban were associated with reduced risk of SSE (RR 0.57, 95% CI: 0.46-0.72) and all-cause mortality (RR 0.73, 95% CI:0.63-0.83), although substantial heterogeneity was present. Exploratory dose-stratified analyses suggested both standard- and low-dose apixaban regimens were associated with favorable efficacy and hemostatic safety relative to warfarin. Consistent numerical trends were observed in the RCT-only analysis, though none reached statistical significance owing to limited sample size. In conclusion, apixaban and rivaroxaban are associated with lower risks of bleeding compared with VKAs in patients with AF and ESRD. However, evidence regarding their efficacy in preventing SSE, all-cause mortality and the optimal apixaban dosing regimen remains inconclusive and requires validation in large, dedicated RCTs.
15 May 2026
Read appraisal →Blood advances
Novel use of a hash-based tokenization for sharing sickle cell disease data without sharing protected health information
Efforts to improve care for people living with sickle cell disease (SCD) have led to the development of several registries; however, many are dependent on time-limited funding and lack coordination. Consequently, existing data sets are fragmented and do not provide the comprehensive, longitudinal insights achievable through well-integrated registries. Although relevant data exist within electronic medical records across institutions, aggregation is limited by poor interoperability, inconsistent use of common data elements, and poor translation of natural language into codified data. These barriers hinder population-level research and contribute to gaps in understanding the lifelong progression of SCD. Creating a new common data system risk losing years of valuable data, highlighting the need to optimize existing data resources. This study aimed to develop a privacy-preserving method to securely link 3 of the largest SCD data collection efforts in the United States. Conducted at the University of Alabama at Birmingham Lifespan Sickle Cell Center, the study leveraged institutional review board-approved access to the Sickle Cell Data Collection project, the American Society of Hematology Research Collaborative Data Hub, and the Globin Research Network for Data and Discovery. Identity tokens were generated and hashed using Secure Hash Algorithm (SHA)-256 to enable secure linkage without sharing protected health information. A total of 8026 records were identified across the 3 registries. Deterministic matching of hashed tokens identified 1080 unique individuals appearing in at least 2 data sets. This study demonstrates the first privacy-preserving linkage of multiple SCD registries. Secure data integration enhances interoperability and enables richer longitudinal analyses critical for advancing SCD research and treatment development.
15 May 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Acupuncture for chemotherapy-induced dysgeusia (AcuDysg): a randomized controlled trial
PURPOSE: The study investigated the effectiveness of dysgeusia-specific acupuncture combined with self-acupressure compared to supportive acupuncture and self-acupressure for chemotherapy-induced dysgeusia in cancer patients with cancer-related fatigue (CRF) and dysgeusia. METHODS: This multicenter, randomized, controlled, two-armed parallel-group, single-blind trial included cancer patients with CRF and dysgeusia during chemotherapy. All participants received CRF treatment consisting of eight acupuncture sessions over 8 weeks and had access to an eLearning course for self-acupressure. Patients in the intervention group received additional dysgeusia-specific acupuncture treatment and an eLearning with instructions to acupressure points, whereas the control group received an intervention focused solely on addressing CRF. The main outcome was perceived dysgeusia over 8 weeks, measured weekly after each acupuncture session on a numeric rating scale from 1 to 10. Other outcomes included taste and smell tests, and assessments of perceived dysgeusia, fatigue, distress, and quality of life. Due to a small sample size, results can be only judged exploratory. The study was approved by the Cantonal Ethics Committee (CEC) (Kanton Zürich Kantonale Ethikkommission) (approval no. KEK-ZH-Nr. 2020-01900). RESULTS: Since we included only twenty-one patients (11 intervention, 10 control, 90% female) instead of the target sample size of 130, no confirmatory effectiveness analyses were conducted. All participants showed a substantial decrease in dysgeusia over time, regardless of treatment type (estimated mean reduction per session - 0.30; 95% CI - 0.43 to - 0.18), reflecting a 0.30-point reduction per session. Quality of life and cancer-related fatigue improved over time. The exploratory analyses did not show substantial differences between groups in any outcomes. No serious adverse events occurred. CONCLUSIONS: Exploratory findings showed no substantial differences between the study groups in perceived dysgeusia, but both study groups improved over time. TRIAL REGISTRATION NUMBER: DRKS00023348 at 03.11.2020, SNCTP000004128.
14 May 2026
Read appraisal →Blood advances
Early mortality with bispecific antibody therapy in RRMM: an IMWG immunotherapy database real-world analysis
Recent therapeutic advances, including bispecific antibodies (bsAbs), have improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM). However, early mortality (EM) remains a significant challenge, even in the era of novel immunotherapies. We conducted a multicenter, retrospective analysis of real-world patients with RRMM treated with commercial bsAbs to evaluate the incidence and causes of EM. Between May 2022 and June 2025, a total of 441 patients were treated across 7 countries. EM, defined as death within 12 months of therapy initiation, occurred in 148 patients (34%), with a median time from bsAb initiation to death of 2.87 months (interquartile range, 1.38-6.85). The leading cause of EM was progressive disease (72%), followed by infection (13%); regardless of the cause of death, 82% had active disease at the time of death. Our findings highlight that despite encouraging efficacy, EM remains high among real-world bsAb recipients, emphasizing the need for improved disease control strategies and supportive care interventions.
13 May 2026
Read appraisal →Blood advances
Belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone for relapsed or refractory multiple myeloma
Belantamab mafodotin (belamaf), an antibody-drug conjugate targeting B-cell maturation antigen, has demonstrated single-agent activity in relapsed/refractory multiple myeloma (RRMM) but is associated with ocular toxicity. This phase 1/2 study evaluated the safety and preliminary efficacy of belamaf administered every 8 weeks in combination with carfilzomib, lenalidomide, and dexamethasone (KRd-b) in patients with RRMM. Eligible patients had received at least 1 previous line of therapy and had not progressed on full-dose lenalidomide. In the dose-escalation phase (3+3 design), belamaf was administered at 1.4 or 1.9 mg/kg every 8 weeks. The recommended phase 2 dose was 1.9 mg/kg, with no dose-limiting toxicities at this level. Among 19 patients treated, the overall response rate was 89.5%, and 78.9% achieved very good partial response or better, with minimal residual disease negativity in all complete responders. At a median follow-up of 19.3 months, 24-month progression-free survival and overall survival rates were 74.3% and 85.1%, respectively. Keratopathy occurred in 94.7% of patients but was mostly grade 1 to 2, reversible, and manageable without permanent discontinuation. Grade ≥3 keratopathy (31.6%) was comparable with historical rates despite the less frequent dosing. Other adverse events, including hematologic and gastrointestinal toxicities, were manageable and consistent with known profiles of KRd or belamaf. The combination demonstrated deep and durable responses, including in patients at high-risk and with lenalidomide maintenance dose-refractory disease. These results support the feasibility of KRd-b with extended-interval belamaf and warrant further evaluation in phase 2 trials to confirm its clinical benefit in RRMM. This trial is registered at www.clinicaltrials.gov as NCT04822337.
13 May 2026
Read appraisal →Psychological medicine
Risk factors associated with blood dyscrasia during clozapine treatment: a systematic review and meta-analysis
Clozapine is the only effective treatment for treatment-resistant schizophrenia, but concerns over blood dyscrasia and need for monitoring limit its use. Evidence suggests many hematological abnormalities may result from surveillance bias, with agranulocytosis being the primary adverse effect directly induced by clozapine. This systematic review (PROSPERO: CRD42024487199) investigates non-genetic risk factors associated with blood dyscrasia during clozapine treatment, focusing on neutropenia and agranulocytosis. Random-effect meta-analyses were performed on studies reporting quantitative risk data. Due to inconsistent neutropenia definitions, analyses used absolute neutrophil count (ANC) thresholds of <2000/mm3, <1500/mm3, and <500/mm3. Forty-four studies were included in the systematic review, 15 in meta-analyses. No significant association was found between agranulocytosis and female gender (OR = 1.48, 95% CI: 0.92-2.38; p = 0.106) or age (pooled standardized mean difference [SMD] = 0.32, 95% CI: -0.26 to 0.90, p = 0.285), whilst a modest inverse association with clozapine dose (SMD = -0.32, 95%CI: -0.50 to -0.14, p < 0.001) and baseline white cell count (SMD = -0.21, 95%CI: -0.40 to -0.03, p = 0.026) was found. Neutropenia (ANC < 2000/mm3) was positively associated with concomitant psychotropic use (OR = 2.15, 95% CI: 1.13-4.07, p = 0.019). Clozapine rechallenge studies revealed no significant associations with gender, age, duration of initial clozapine trial, or length of discontinuation period prior to rechallenge. No strong predictors of clozapine-associated blood dyscrasia were identified. Findings may be limited by study variability, surveillance bias, and lack of consistent differentiation between agranulocytosis and milder neutropenia, highlighting limitations in current evidence.
13 May 2026
Read appraisal →European journal of clinical pharmacology
The impact of gene polymorphisms on the response of methotrexate-based treatments
PURPOSE: Methotrexate (MTX) is a long-standing drug used to treat leukemia (at high doses to inhibit DNA/RNA synthesis) and rheumatoid arthritis (at low doses for anti-inflammatory effects). Its characteristic narrow therapeutic range, in terms of efficacy and safety associated with MTX, are important factors to consider when deciding whether to prescribe it. A major challenge in its use is interindividual variability which is largely attributed to germline genetic polymorphisms in genes encoding proteins that control the pharmacokinetics or pharmacodynamics of MTX. METHODS: This study updates a previous 2018 review using a systematic literature search in PubMed/MEDLINE, Scopus, and SciELO. The search, conducted according to the PRISMA protocol, employed predefined keywords to identify studies published up to June 2025. RESULTS: This systematic review identified that, to date, only a few genetic polymorphisms influence clinical decision-making. Specifically, the MTHFR 677T allele and the MTHFR 677T-1298 A haplotype (rs1801133- rs1801131) have been associated with toxicity in both adults and children. Furthermore, the 677T-1298 A haplotype has been linked with reduced event-free survival in Caucasian patients with either adult RA or pediatric ALL. Regarding other markers, the TYMS rs34743033 3R allele has been implicated with reduced efficacy in adult patients receiving low-dose MTX, while the FPGS rs1544105 T allele has shown an association with diverse toxicities in ALL pediatric patients. CONCLUSION: Although considerable research has been conducted and numerous results have been obtained, the available evidence remains predominantly of moderate quality. Consequently, current guidelines from CPIC and the DPWG do not recommend routine MTX dose adjustments based solely on single gene variants. It is, therefore, imperative to develop and validate multifactorial risk prediction tools that integrate a range of other clinical factors. Accordingly, the establishment of a comprehensive pharmacogenetics-guided dosing guideline for MTX remains an elusive goal.
13 May 2026
Read appraisal →PloS one
Machine learning-based model for predicting recanalization in isolated distal deep vein thrombosis and analysis of predictors
BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is common, yet tools for predicting poor recanalization remain limited. We aimed to develop and compare machine learning models for predicting poor recanalization in patients with IDDVT and to identify the most informative predictors. METHODS: A total of 1600 patients with IDDVT were retrospectively enrolled. The dataset was randomly divided into a development set (n = 1280) and an independent test set (n = 320) using stratified sampling. Six predictive models were developed and compared: logistic regression (LR), support vector machine (SVM), random forest (RF), multilayer perceptron (MLP), extreme gradient boosting (XGBoost), and a Voting Ensemble. Model training and hyperparameter tuning were performed in the development set using five-fold stratified cross-validation, and optimal classification thresholds were determined using the Youden index. Model performance was evaluated by discrimination, calibration, and classification metrics, with 95% confidence intervals estimated by bootstrap resampling (10,000 iterations). SHAP analysis was applied to interpret the final model. RESULTS: In the independent test set, all models showed acceptable to strong discrimination, with AUC values ranging from 0.808 to 0.908. XGBoost achieved the best overall performance, with an optimal threshold of 0.183, an AUC of 0.908 (95% CI, 0.855-0.952), a Brier score of 0.077 (95% CI, 0.058-0.096), an accuracy of 0.900 (95% CI, 0.866-0.931), a precision of 0.650 (95% CI, 0.529-0.767), a recall of 0.803 (95% CI, 0.686-0.906), an F1-score of 0.717 (95% CI, 0.615-0.806), and a specificity of 0.918 (95% CI, 0.884-0.950). The calibration intercept and slope of the XGBoost model were 0.149 (95% CI, -0.192 to 0.454) and 1.410 (95% CI, 1.098-1.809), respectively, indicating acceptable overall calibration. SHAP analysis identified D-dimer rate, provoking-factor-related variables, anticoagulant use, and age group as the most influential predictors. CONCLUSION: Among six candidate models, XGBoost showed the best overall performance for predicting poor recanalization in patients with IDDVT. This study establishes an interpretable machine learning-based prediction framework focused specifically on poor recanalization in IDDVT and highlights the contribution of dynamic laboratory information, particularly D-dimer rate. The model may support early risk stratification and individualized follow-up planning, but external validation is required before routine clinical implementation.
13 May 2026
Read appraisal →Med (New York, N.Y.)
Evaluation of recombinant human prourokinase for acute pulmonary embolism: A phase 2, randomized clinical trial
BACKGROUND: Recombinant human prourokinase (rhPro-UK) is a novel plasminogen activator under investigation for acute pulmonary embolism (aPE). We aimed to explore the efficacy and safety of rhPro-UK vs. alteplase (recombinant tissue plasminogen activator [rt-PA]) in patients with aPE. METHODS: In this phase 2, randomized, single-blind, multicenter, active-controlled, randomized trial involved eighteen centers from university-affiliated tertiary hospitals across China. Patients aged 18-75 years with high or intermediate-to-high risk aPE were randomized to receive intravenous rhPro-UK (40 mg, n = 37; 50 mg, n = 35) or rt-PA (n = 35) and were followed for 7-30 days. The primary efficacy outcome was the change from baseline in systolic pulmonary artery pressure (sPAP) at 24 h post-treatment. Secondary outcomes include changes in right ventricular function parameters. Safety outcomes include all-cause mortality, recurrent PE, hemodynamic deterioration within 7 days, and bleeding events within 30 days. FINDINGS: All treatment groups showed a reduction in sPAP at 24 h (mean change: 40 mg rhPro-UK, -13.40 mmHg [95% confidence interval (CI): -24.10 to -2.71]; 50 mg rhPro-UK, -15.42 mmHg [95% CI: -25.93 to -4.91], and rt-PA: -16.02 mmHg [95% CI: -25.53 to -6.51]), with improvements sustained through 30 days. The incidence of non-major bleeding events was numerically lower in the rhPro-UK groups (40 mg: 63.9%; 50 mg: 55.6%) compared to the rt-PA group (82.9%; p = 0.04). Two deaths occurred, each in the 40 mg rhPro-UK group and rt-PA group. CONCLUSION: rhPro-UK tended to result in early hemodynamic improvement comparable to rt-PA and seemed to have a numerically lower risk of non-major bleeding events. The ClinicalTrials.gov identifier is NCT03108833. FUNDING: This work was funded by Tasly Biopharmaceuticals Co., Ltd.
12 May 2026
Read appraisal →The New England journal of medicine
Base Editing of HBG1 and HBG2 Promoters for Sickle Cell Disease
BACKGROUND: Sickle cell disease is characterized by chronic hemolytic anemia and recurrent severe vaso-occlusive crises. Ristoglogene autogetemcel (risto-cel) includes autologous CD34+ hematopoietic stem and progenitor cells that have been base-edited to target the HBG1 and HBG2 promoters and inhibit BCL11A binding without altering BCL11A expression, yielding a switch in hemoglobin production from sickle hemoglobin (HbS) to antisickling fetal hemoglobin (HbF). METHODS: In this phase 1-2 study, we enrolled patients 12 to 35 years of age with sickle cell disease who had had at least four severe vaso-occlusive crises in the 2 years before enrollment. After myeloablative conditioning with pharmacokinetically guided administration of busulfan, patients received a single infusion of risto-cel (at a dose of ≥3.0×106 viable CD34+ cells per kilogram of body weight). The primary efficacy end point was freedom from severe vaso-occlusive crises for 12 consecutive months, starting later than 60 days after the last red-cell transfusion. This interim analysis was unplanned; here, we describe safety, editing, engraftment, and hemoglobin production and the number of severe vaso-occlusive crises starting later than 60 days after the last red-cell transfusion. RESULTS: A total of 31 patients received risto-cel and were followed for a mean of 6.6 months (range, 0.3 to 20.4). A median of one cycle (range, one to five) was required for stem-cell collection. Neutrophil engraftment occurred at a median of 17.5 days, and platelet engraftment at a median of 19 days. One patient died from idiopathic pneumonia syndrome. All 31 patients had at least one adverse event, 27 (87%) had an adverse event of grade 3 or higher, and 12 (39%) had a serious adverse event. At 6 months, the mean fraction of on-target edited alleles in peripheral blood was 67.4%, the mean HbF as a fraction of total hemoglobin was more than 60%, and the HbS as a fraction of total hemoglobin was less than 40% (among 13 patients); these levels were maintained throughout follow-up. No investigator-reported severe vaso-occlusive crises occurred later than 60 days after the last red-cell transfusion. CONCLUSIONS: Treatment with risto-cel was followed by rapid engraftment and durable expression of HbF and reduction in HbS. These data support further investigation of risto-cel to treat sickle cell disease. (Funded by Beam Therapeutics; BEACON ClinicalTrials.gov number, NCT05456880.).
12 May 2026
Read appraisal →Blood
Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia.
Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia (TDT) involves autologous transplantation of hematopoietic stem and progenitor cells transduced with a modified β-globin gene to produce functional adult hemoglobin (Hb) containing βA-T87Q-globin (HbAT87Q). Sixty-three participants with TDT (median age, 17 years [range, 4-35]) received beti-cel in phase 1/2 (n = 22) or phase 3 (n = 41) studies and enrolled in the long-term follow-up LTF-303 study (median follow-up, 5.9 years [range, 2.9-10.1]). Manufacturing refinements in phase 3 increased transduction efficiency, resulting in higher drug product vector copy number and HbAT87Q levels, which translated into higher Hb and transfusion independence (TI) rates than in phase 1/2. TI was achieved by 15 of 22 (68.2%) phase 1/2 participants (median weighted average Hb during TI, 10.2 g/dL) and 37 of 41 (90.2%) of phase 3 participants (median, 11.2 g/dL), and was sustained through last follow-up. Treatment efficacy was similar across ages and TDT genotypes. Among participants achieving TI, 38 of 52 (73%) had discontinued iron chelation at last follow-up, with no increase in liver iron concentration. Markers of ineffective erythropoiesis, including serum transferrin receptor and erythropoietin, improved with restoration of iron homeostasis. Health-related quality-of-life assessment scores showed durable improvements. No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported. These findings establish beti-cel as a durable, 1-time therapy that achieves TI, restores iron balance, and improves quality of life, offering a potentially curative treatment option for people with TDT. This trial was registered at www.clinicaltrials.gov as NCT02633943.
11 May 2026
Read appraisal →European heart journal
Temporal modulation of antiplatelet therapy in high-risk patients undergoing complex percutaneous coronary intervention: the TAILORED-CHIP randomized clinical trial
BACKGROUND AND AIMS: Limited data exist on optimal antiplatelet strategies for high-risk patients undergoing complex percutaneous coronary intervention (PCI). This study aimed to investigate the efficacy and safety of tailored antiplatelet treatment with temporal modulation of the intensity of platelet inhibition in patients undergoing complex high-risk PCI. METHODS: We randomly assigned 2018 patients with high-risk anatomical or clinical characteristics undergoing complex PCI to a tailored antiplatelet strategy with early escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin <6 months) and late de-escalation (clopidogrel monotherapy >6 months) or dual antiplatelet therapy (clopidogrel plus aspirin for 12 months). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, stent thrombosis, unplanned urgent revascularization, and clinically relevant bleeding (Bleeding Academic Research Consortium Type 2, 3, or 5) at 12 months. RESULTS: The mean age was 64.0 years, 22.6% had left main PCI, 19.5% had complex bifurcation PCI, 84.1% had diffuse long lesions, 93.7% had multivessel PCI, and 36.7% had medically treated diabetes. At 12 months, a primary outcome event occurred in 105 patients (10.5%) assigned to tailored antiplatelet therapy and in 89 patients (8.8%) assigned to dual antiplatelet therapy [hazard ratio, 1.19; 95% confidence interval (CI), 0.90-1.58; P = .21]. The incidence of major ischaemic events appeared to be similar in both groups. The incidence of clinically relevant bleeding at 12 months was 7.2% in the tailored-therapy group and 4.8% in the dual-therapy group (difference, 2.45% points; 95% CI, 0.37-4.53). CONCLUSIONS: Among high-risk patients undergoing complex PCI, tailored antiplatelet strategy with early escalation and late de-escalation, as compared with dual antiplatelet therapy, did not decrease the incidence of primary net adverse events at 12 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03465644.
11 May 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Modified Frailty Index-11 (mFI-11) measured frailty as a predictor of post-transplant outcomes in non-Hodgkin's lymphoma patients undergoing hematopoietic stem cell transplantation: a retrospective analysis of National Inpatient Sample database
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a critical treatment for non-Hodgkin lymphoma (NHL) but involves significant post-transplant risks. Frailty, measured by the Modified Frailty Index-11 (mFI-11), may influence outcomes. METHODS: We analyzed NHL patients undergoing autologous or allogeneic HSCT from the Nationwide Inpatient Sample (2016-2020). Frailty was defined by mFI-11, and outcomes included in-hospital mortality, unfavorable discharge, prolonged length of stay (LOS), complications, and costs. Multivariable regression models with stratification by age and Charlson Comorbidity Index were applied. RESULTS: Of 2807 patients (ages 18-85), frail patients were older and had more comorbidities. In autologous HSCT, frailty was linked to higher mortality (2.02% vs. 0.27%, p < 0.001), increased unfavorable discharges (19.75% vs. 10.80%, p < 0.0001), and prolonged LOS (15.92% vs. 7.75%, p < 0.0001). Similar trends were observed in the allogeneic cohort. CONCLUSIONS: Frailty predicts worse post-transplant outcomes in NHL patients undergoing HSCT, emphasizing the need for pre-transplant frailty screening.
10 May 2026
Read appraisal →European journal of heart failure
Erythropoiesis-stimulating agents to reduce heart failure hospitalization: a systematic review and meta-analysis
AIMS: Anaemia is common in patients with chronic heart failure (CHF), worsening functional status and prognosis. The role of erythropoiesis-stimulating agents (ESAs) to reduce hospitalization remains unclear. METHODS AND RESULTS: A pre-registered systematic search was performed of randomized controlled trials in adults with CHF and anaemia, comparing any ESA at any dose versus placebo or no treatment.Fourteen trials were included with 3128 participants, with moderate quality of evidence for most outcomes and variable risk of bias. Meta-analysis during 5604 person-years of follow-up demonstrated no significant difference in first CHF hospitalization comparing ESAs with control: Peto odds ratio (OR) 0.93, 95% CI 0.78-1.10, P = .37; trial heterogeneity I2 = 36%. ESAs significantly reduced total CHF hospitalization with 622 events/2698 person-years, compared with 761/2914 person-years for control: incidence rate ratio 0.81, 95% CI 0.73 to 0.90, P < .001; no heterogeneity between trials, I2 = 0%. There were no significant differences between treatment groups for all-cause mortality (OR 1.01, 95% CI 0.86-1.18, P = .88; I2 = 35%) or incident adverse events. Patients randomized to ESAs increased their haemoglobin level [mean difference (MD) 1.6 g/dL compared with control, 95% CI 1.6-1.7, P < .001] and exercise tolerance (MD 69 metres, 95% CI 17-122, P = .009), with lower NYHA class on follow-up (MD -0.73 class, 95% CI -1.11 to -0.36, P < .001). CONCLUSION: ESA treatment in patients with CHF and mild anaemia can reduce recurrent CHF hospitalization and improve functional capacity, without any impact on adverse events. Including ESAs in CHF management could be considered in patients with anaemia at high risk of recurrent hospital admissions.
10 May 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Prevalence of antibody drug conjugated-induced nausea and vomiting (ADCINV) in patients with cancer
INTRODUCTION: Antibody-drug conjugates (ADC) have emerged as an important part of systemic treatment across disease sites. To date, there is no robust pooled prevalence estimate of nausea and vomiting induced by ADCs. Establishing such estimates is essential to determine if ADC-induced nausea and vomiting (ADCINV) represents a clinically significant problem warranting further research into antiemetic prophylaxis. Our aim is to report the prevalence of reported ADCINV across literature. METHODS: A systematic search of Medline, Embase, Cochrane CENTRAL and Web of Science was conducted from database inception until September 24, 2025. Articles were included if they reported nausea and/or vomiting due to ADCs used in cancer treatment, in the abstract. Pooled prevalence was reported. Subgroup analysis was conducted by ADC. Meta-regression was conducted by age and sex. Quality assessment was conducted. Type I error was set at 0.05. RESULTS: A total of 209 studies with 15,493 patients were included. Thirty-nine percent (95%CI, 36-42%) of patients experience any nausea, and 26% (95%CI, 23-29%) experience any vomiting. Younger patients are more likely to experience nausea; each 10-year increase in age is associated with a 12% decrease in nausea rates. Higher emetogenic ADCs include trastuzumab deruxtecan, sacituzumab govitecan, brentuximabvedotin and patritumab deruxtecan. Lower emetogenic agents include disitimab vedotin, telisotuzumab vedotin and rovalpituzumab tesirine. DISCUSSION: This is the first study to report prevalence of ADCINV across ADCs. It is a prevalent adverse effect akin to chemotherapy-induced nausea and vomiting that should be viewed as clinically relevant and further investigated to help develop optimal strategies related to antiemetics.
10 May 2026
Read appraisal →European journal of hospital pharmacy : science and practice
Algorithm-managed dosing and pharmacist-managed dosing of erythropoietin stimulating agents in renal anaemia: a systematic review
OBJECTIVES: The goal of this systematic review was to identify and summarise algorithm-managed and pharmacist-managed dosing of erythropoietin stimulating agents (ESA) in patients with renal anaemia and to determine the effects on available outcome parameters. METHODS: We followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines for systematic reviews. Studies investigating algorithm-managed and pharmacist-managed dosing of ESA in adult patients with renal anaemia were evaluated for inclusion. No restrictions were set on outcome parameters. Observational and interventional studies available as full-text articles with a control group and follow-up ≥6 months were eligible for inclusion. Relevant databases were searched from their inception through August 2024. Two independent reviewers evaluated all studies. The risk of bias was assessed by the ROBINS-I and RoB1 tools. The protocol of this study was registered in PROSPERO (CRD42021243678). RESULTS: After screening 140 articles, 17 articles and 4313 patients could be included. Available evidence was of low to moderate quality with a high risk of bias. Data were summarised and tabulated. Meta-analysis was not possible due to the substantial heterogeneity in participants, study design, interventions, comparisons, and outcome parameters. However, standardised metrics could be identified and calculated for haemoglobin and ESA dose. The percentage in target range for haemoglobin varied between 3.5% lower (95% CI -18.67% to +11.67%) to 32.0% higher (95% CI 14.07% to 49.93%) in the pharmacist-managed group versus the control group (n=1401). The range in reduction in ESA dose was 5.45% (95% CI -7.97% to +18.87%) to 49.97% (95% CI 20.32% to 79.61%) in the pharmacist-managed group versus the control group (n=2115). CONCLUSION: Low-quality data with high risk of bias suggest that pharmacist-managed renal anaemia may improve the percentage of haemoglobin within target range and reduce the ESA dose. However, meta-analysis was impossible due to substantial heterogeneity. Therefore, no definite conclusions could be drawn on the effectiveness of pharmacist-managed dosing of ESA in renal anaemia. PROSPERO REGISTRATION NUMBER: CRD42021243678.
26 Apr 2026
Read appraisal →Blood
A phase 1/2 study of donor-derived anti-CD33 CAR T-cell therapy (VCAR33) for relapsed/refractory AML after allogeneic HCT
VCAR33, a donor-derived CD33-directed chimeric antigen receptor T-cell (CAR T) product, was developed to decrease relapse of high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation (alloHCT). We describe preclinical characterization of the VCAR33 construct, which was optimized for long-term antitumor surveillance based on killing and persistence assays. Prior to its use in post-alloHCT maintenance, we evaluated safety and efficacy of VCAR33 in a phase 1/2 clinical study for adults with relapsed or measurable residual disease (MRD)-positive CD33+ AML/MDS after alloHCT. Fifteen patients received VCAR33 across 2 arms stratified by disease burden: 7 patients in arm A (bone marrow blasts ≥5%) at dose level 1 (DL1; 1 × 106 CAR+ Ts per kg) and 8 patients in arm B (bone marrow blasts <5%) at DL1 (n = 5) and DL2 (3 × 106 CAR+ Ts per kg; n = 3). The study ended for nonsafety reasons before escalation to DL3 (1 × 107 CAR+ Ts per kg) and maximum tolerated dose was not determined. The most common treatment-related adverse event was cytokine release syndrome (93.3%; all <grade 3). Four patients (26.7%) experienced immune cell-associated neurotoxicity syndrome (1 ≥grade 3) and 1 patient (6.7%) had grade 3 acute graft-versus-host disease within 28 days of VCAR33 infusion. Fourteen patients (93.3%) had transient VCAR33 expansion. Overall response rate was 20%: 2 patients had complete remission with incomplete count recovery in arm A and 1 arm B patient achieved MRD clearance. This allogeneic CAR T product demonstrated acceptable safety and preliminary antileukemic activity. This trial was registered at www.clinicaltrials.gov as #NCT05984199.
25 Apr 2026
Read appraisal →Renal failure
Dapagliflozin improves hemoglobin and anemia in chronic kidney disease: a systematic review and meta-analysis
Anemia becomes increasingly prevalent as kidney function declines. Current treatments carry multiple safety risks. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), dapagliflozin, have emerged as background anemia modulator, a promising alternative, showing protective effects against anemia. This study synthesizes evidence on dapagliflozin's potential to improve anemia in chronic kidney disease (CKD) patients. A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, including eight studies identified from six databases. Risk of bias was assessed using tools appropriate for each study design (RoB 2, NOS, JBI). Data were pooled using a random-effects model with RevMan 5.4. The primary analysis for hemoglobin demonstrated significant increase (MD = 4.37; 95% CI = 0.71-8.03; p = 0.02) and remained significant in the sensitivity analysis (MD = 4.11; 95% CI = 0.19-8.04; p = 0.04). A sensitivity analysis for hematocrit revealed a highly significant increase (MD = 2.15; 95% CI = 1.86-2.44; p < 0.00001). In the sensitivity analysis for adverse events dapagliflozin significantly reduced the overall risk (RR = 0.77; 95% CI = 0.59-0.99; p = 0.04). This finding was associated with significantly lower mortality (RR = 0.67; p = 0.02), while no significant differences were observed for cardiovascular (p = 0.22) or genitourinary events (p = 0.70). Dapagliflozin is associated with clinically meaningful improvements in hemoglobin and anemia outcomes in CKD. These findings suggest a potential erythropoietic benefit beyond glycemic control, although dedicated anemia-focused trials are needed to confirm clinical applicability.
25 Apr 2026
Read appraisal →European heart journal
Predictors of recurrent venous thromboembolism and bleeding in patients with cancer: a meta-analysis
BACKGROUND AND AIMS: Patients with cancer and venous thromboembolism (VTE) have a high risk of recurrent VTE and anticoagulant-related bleeding. This study aimed to identify prognostic factors for these complications. METHODS: A systematic review was performed for randomized trials and cohort studies evaluating prognostic factors for recurrent VTE or anticoagulant-related bleeding in adult patients with cancer and VTE. Adjusted hazard ratios (aHRs) for factors were pooled using random-effects meta-analysis. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Thirty-three studies (n = 96 753) were included in the meta-analyses. Factors with high certainty of association with increased risk of recurrent VTE included a previous history of VTE [aHR 1.50 (95% CI 1.08-2.09)], Eastern Cooperative Oncology Group (ECOG) performance status >0 [1.81 (1.34-2.46)] or >1 [2.44 (1.55-3.84)], advanced cancer [1.38 (1.15-1.65)], and specific cancer sites including lung [1.78 (1.29-2.46)], hepatobiliary [2.37 (1.70-3.30)], pancreas [3.20 (2.06-4.96)], and genitourinary [1.38 (1.14-1.67)]. Conversely, recent surgery [aHR 0.56 (95% CI 0.40-0.76)] and breast cancer [0.43 (0.23-0.81)] had a high certainty of association with a decreased risk. Factors with a high certainty of association with an increased risk of anticoagulant-related bleeding included a history of bleeding [aHR 2.41 (95% CI 1.50-3.88)], ECOG performance status ≥2 [2.10 (1.48-2.99)], advanced cancer [1.60 (1.29-1.97)], and cancers of the brain [2.25 (1.64-3.09)], gastrointestinal system [1.74 (1.44-2.11)], genitourinary system [1.90 (1.48-2.45)], and prostate [1.72 (1.26-2.34)]. CONCLUSIONS: The prognostic factors identified in this meta-analysis should be considered as part of risk stratification frameworks for anticoagulation management in patients with cancer and VTE.
24 Apr 2026
Read appraisal →European heart journal
Pre-treatment lysis time of plasma-derived fibrin clots and bleeding in patients on oral anticoagulants for atrial fibrillation in the ARISTOTLE trial
BACKGROUND AND AIMS: Oral anticoagulation reduces stroke risk in patients with atrial fibrillation (AF) but increases bleeding. Longer fibrin clot lysis time has been shown to predict adverse cardiovascular outcomes in acute coronary syndromes. This study explored relationships between fibrin clot lysis time at randomization and clinical outcomes in patients with AF enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in AF (ARISTOTLE) trial. METHODS: Plasma samples were obtained from anticoagulation-naïve participants, before initiation of study medication (n = 1841). Fibrin clot turbidimetry was performed, and lysis time determined. Associations between lysis time and characteristics, biomarkers, and on-treatment bleeding and cardiovascular events were assessed by lysis time quartile (Q1-4, shortest to longest). RESULTS: A shorter lysis time was associated with being older, male, permanent AF, lower body mass index, estimated glomerular filtration rate and C-reactive protein, and higher N-terminal pro-B-type natriuretic peptide. Major and clinically relevant non-major bleeding was significantly more frequent in lysis time Q1 vs. Q4 [6.3%/yr vs. 2.1%/yr; HR, 2.99 (95% CI, 1.75-5.12); P = .001], including after multifactorial adjustment [HR, 2.61 (1.45-4.69); P = .016]. Those in Q2 and Q3 had intermediate bleeding risk vs. Q4 [HR, 2.21 (1.27-3.87); 2.08 (1.18-3.66) respectively], suggesting a graduated effect. Treatment allocation to apixaban vs. warfarin did not affect the relationship between lysis time and bleeding (interaction-P = .80). There was no significant association between lysis time and a composite of cardiovascular death, stroke, systemic embolism or myocardial infarction. CONCLUSIONS: Shorter pre-treatment fibrin clot lysis time independently predicted higher bleeding risk in patients receiving oral anticoagulation for AF.
24 Apr 2026
Read appraisal →European heart journal
Venous thromboembolism and bleeding in cancer patients: role of inflammatory and cardiac biomarkers.
BACKGROUND AND AIMS: Patients with cancer have increased risk of venous thromboembolism (VTE) and bleeding. Inflammatory and cardiac biomarkers may predict these complications, but their role remains unclear. This study examined associations between two inflammatory-related markers (C-reactive protein and growth differentiation factor-15) and two cardiac markers [N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-TnT)] with VTE and clinically relevant bleeding in cancer patients. METHODS: A post hoc analysis of the AVERT trial, which evaluated apixaban for VTE prevention in ambulatory cancer patients with a Khorana score of ≥2, was performed. Biomarkers were measured at baseline and 1 month, with C-reactive protein also at 3 months. Fine and Gray regression, accounting for competing risk of death and adjusted for age and advanced cancer, estimated subdistribution hazard ratios (SHRs) for VTE and clinically relevant bleeding. RESULTS: Of 574 patients, 514 provided baseline samples. One- and 3-month samples were available from 454 and 447, and 378 and 364, patients without prior VTE and bleeding events, respectively. Elevated baseline growth differentiation factor-15 was associated with increased VTE risk [SHR 1.36, 95% confidence interval (CI) 1.01-1.84]. N-terminal pro-B-type natriuretic peptide (SHR 1.44, 95% CI 1.08-1.92) and C-reactive protein (SHR 1.38, 95% CI 1.07-1.76) were linked to bleeding risk. Increasing high-sensitivity troponin T from baseline to 1 month was associated with higher VTE risk (SHR 1.89, 95% CI 1.14-3.16). Nomograms were developed to estimate VTE and clinically relevant bleeding risks. CONCLUSIONS: Select inflammatory-related and cardiac markers were associated with VTE and bleeding risks in cancer patients, which can be determined using developed nomograms. Prospective research is needed to confirm these findings.
23 Apr 2026
Read appraisal →mSystems
Short-chain fatty acid-producing microbes differentiate non-infectious and infectious neutropenic fever in leukemia.
UNLABELLED: Neutropenic fever (NF) is often the first sign of infection in patients with hematologic malignancies, but its cause is frequently unknown, leading to broad-spectrum antibiotic use without confirmed infections. Although research links gut microbiome disruptions to treatment-related infections, it typically examines NF as the outcome, leaving a gap in understanding how the microbiome and metabolic factors distinguish infectious from non-infectious cases. Stool samples from acute myeloid leukemia patients were analyzed to characterize gut microbiome composition and fecal metabolites at baseline and at fever onset. Machine learning models, network analyses, and functional profiling were used to differentiate infectious NF vs non-infectious NF at baseline and at fever onset. The baseline model (area under the receiver operating characteristic [AUROC] = 0.769) identified higher levels of Akkermansia, Enterobacter, Escherichia-Shigella, and Flavonifractor as predictors of infectious NF, while Collinsella, Lachnospiraceae, Coprococcus, and acetic acid were linked to non-infectious cases. At fever onset, Enterococcus was enriched in infectious NF, whereas Gemella, Butyrate, Lachnospiraceae, Ruminococcaceae, and Eisenbergiella abundances favored non-infectious NF outcomes (AUROC = 0.752). Network analyses also revealed greater functional diversity and microbiome-metabolome connectivity in non-infectious cases at fever onset. This study suggests that gut microbiota and metabolites may serve as biomarkers for distinguishing infectious from non-infectious neutropenic fever, warranting further validation in larger cohorts. IMPORTANCE: Our study tackles the challenge of managing neutropenic fever (NF) in immunocompromised patients whose numbers have increased due to various immunodeficiencies and treatments that suppress immune function. Fever is often the only sign of a serious infection in these patients, yet there are neither clear patterns linking risk factors to infection nor biomarkers reliable for ruling out non-infectious causes. As a result, febrile patients are typically empirically treated for major pathogens, even in the absence of confirmed infections, which propagates antimicrobial resistance and gut dysbiosis. Our research utilizes gut microbiome and targeted metabolomic profiling from two cohorts of patients with acute myeloid leukemia undergoing chemotherapy and employs a machine learning framework to distinguish between infectious and non-infectious NFs at baseline and upon fever onset.
23 Apr 2026
Read appraisal →Journal of hematology & oncology
Uncoupling toxicity from efficacy in donor selection for allogeneic hematopoietic cell transplantation: a retrospective cohort study using double machine learning
Haploidentical hematopoietic cell transplantation (HCT) offers potent graft-versus-tumor effects but is historically limited by higher non-relapse mortality (NRM) compared to matched unrelated (MUD) or related donors (MRD). To algorithmically decouple the competing risks of NRM and relapse, we analyzed 1,713 adult patients (MD Anderson discovery cohort) and 6,829 patients (registry replication cohorts) using a double machine-learning framework of Causal Survival Forests to estimate individualized treatment effects, while Random Survival Forests defined absolute prognostic risk. We found biological uncoupling of relapse and NRM: relapse was driven by disease biology, while NRM was governed by physiological reserve. Specifically, cardiovascular or cerebrovascular comorbidities acted as selective amplifiers of haploidentical toxicity-a "vascular penalty" that doubled mortality risk in the bootstrapped model (sub-distribution hazard ratio 2.09, 95% confidence interval 1.26-3.35). We developed a 3-factor nomogram (recipient age, vascular comorbidity, B-leader matching status) to identify an "Optimized Haploidentical" phenotype. Exploratory multivariable modeling suggested MUD consistently maximized predicted disease-free survival across all subgroups. Among haploidentical versus MRD comparisons, B-leader mismatch appeared to favor MRD across ages, while B-leader matched haploidentical donors in older patients (≥ 60 years) modeled near-equivalent DFS to MRD, representing a hypothesis-generating "zone of equivalence" requiring prospective validation.
22 Apr 2026
Read appraisal →PloS one
Global folate deficiency among adolescent girls: A systematic review and meta-analysis
INTRODUCTION: Adolescents have higher nutrient requirements than adults, as this stage accounts for approximately 40% of total adult weight gain, 45% of skeletal mass and about 15% of adult height. Adequate micronutrient intake is particularly essential for adolescent girls to support growth, reproductive health, and cognitive development. Adolescent folate deficiency disrupts hematopoiesis, causing megaloblastic anemia, and hinders growth, cognition, and immune function and becoming a major public health concern. OBJECTIVE: This global systematic review and meta-analysis aims to address the gap in comprehensive evidence on the prevalence of adolescent folate deficiency. METHODS: This systematic review was conducted and reported according to PRISMA guidelines. We conducted a systematic literature search in PubMed, HINARI, Science Direct, DOAJ, Google, and Google Scholar for studies reporting the prevalence of folate deficiency among adolescent girls up to August 2025. Study quality was assessed using the Newcastle-Ottawa Scale, and evidence certainty was evaluated using GRADE. Pooled prevalence estimates with 95% confidence intervals were calculated using a random-effects model (DerSimonian-Laird method). Heterogeneity was assessed with Cochrane Q and I² statistics. Publication bias was evaluated through visual inspection of funnel plots and Egger's regression test, and adjusted estimates were calculated using the trim-and-fill method. Meta-regression analyses were conducted to explore potential sources of heterogeneity. Sensitivity analyses were performed to assess the robustness of pooled estimates. RESULTS: The search strategy identified 1,498 records, of which 26 studies met the eligibility criteria and were included in this systematic review and meta-analysis. The pooled global prevalence of folate deficiency among adolescent girls was 26.9%(95% CI: 20.5-33.2), with substantial heterogeneity observed between studies (I² = 99.99%, p < 0.001). On average across included studies, approximately one-quarter of adolescent girls were classified as folate deficient, though the true prevalence varied markedly between settings.. The pooled prevalence of folate deficiency among adolescent girls varied across regions, with the highest rate observed in Africa at 35.5%. CONCLUSION: These findings revealed folate deficiency as a substantial global public health concern among adolescent girls with a disproportionately high burden in low-resource settings. Region-specific strategies are urgently needed to prevent folate deficiency among adolescent girls, particularly in low-resource settings. Implementing targeted nutritional interventions and public health policies is essential to reduce its associated health consequences in this vulnerable population.
22 Apr 2026
Read appraisal →EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
Impact of renal function on edoxaban antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease: a prespecified analysis of the EPIC-CAD trial
BACKGROUND: Renal function is a critical factor of ischaemic and bleeding risks in patients with atrial fibrillation (AF) receiving antithrombotic therapy. AIMS: This study aimed to evaluate the impact of renal dysfunction in patients with AF and stable coronary artery disease (CAD) undergoing antithrombotic therapy. METHODS: The Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease (EPIC-CAD) trial randomised patients to edoxaban monotherapy or dual antithrombotic therapy (edoxaban plus a single antiplatelet agent). In this prespecified analysis, patients were stratified by creatinine clearance into low (<50 mL/min) or high (≥50 mL/min) groups according to edoxaban dose-reduction criteria. The primary endpoint was net adverse clinical events (NACE: death from any cause, myocardial infarction, stroke, systemic embolism, urgent revascularisation, or major/clinically relevant non-major bleeding) at 12 months. RESULTS: Of 1,040 randomised patients, 252 (24.2%) had low creatinine clearance; these patients were older and had more comorbidities compared with the 788 patients (75.8%) with high creatinine clearance. Patients with low creatinine clearance experienced higher risks of NACE (hazard ratio [HR] 1.72, 95% confidence interval [CI]: 1.19-2.49; p=0.004), ischaemic events (HR 2.70, 95% CI: 1.09-6.70; p=0.032), and bleeding (HR 1.54, 95% CI: 1.01-2.34; p=0.046). At 12 months, edoxaban monotherapy reduced NACE compared with dual therapy in both the low (12.1% vs 21.7%, HR 0.52, 95% CI: 0.28-0.98; p=0.042) and high creatinine clearance groups (5.2% vs 14.5%, HR 0.40, 95% CI: 0.25-0.65; p<0.001), with no interaction (p for interaction=0.53). CONCLUSIONS: In patients with AF and stable CAD, edoxaban monotherapy led to a lower risk of primary NACE than dual antithrombotic therapy, regardless of renal function. (ClinicalTrials.gov: NCT03718559).
21 Apr 2026
Read appraisal →Medicine
Drug-induced neutropenia: A comprehensive pharmacovigilance study of the FAERS database.
Drug-induced neutropenia (DIN) deserves both clinicians' and researchers' attention for the serious clinical consequences. This study aimed to conduct an exploratory analysis of DIN reports in the United States Food and Drug Administration Adverse Event Reporting System database to identify drugs associated with neutropenia. A disproportionality analysis of DIN was conducted using reports submitted to the United States Food and Drug Administration Adverse Event Reporting System from the first quarter of 2004 to the fourth quarter of 2024. Both the reporting odds ratio algorithms and the information component were applied to identify an association between target drugs and DIN events. A total of 223,736 DIN cases were found, and 254 drugs were identified as potentially associated with neutropenia. The top-ranked drug categories were "monoclonal antibodies and antibody-drug conjugates," "other antineoplastic agents," "protein kinase inhibitors," "direct-acting antivirals," "antimetabolites," "alkylating agents," and "immunosuppressants." The top 5 drugs ranked by number of cases were clozapine, lenalidomide, rituximab, palbociclib, and carboplatin. The top 5 drugs ranked by reporting odds ratio signal strength were calcium levofolinate, vinorelbine, gemtuzumab ozogamicin, fludarabine, and daunorubicin. This comprehensive pharmacovigilance study identified drugs potentially associated with neutropenia, which can help clinicians and researchers further understand DIN.
20 Apr 2026
Read appraisal →JMIR cancer
Digital and Paper-Based Hospital Workflows and 60-Day Mortality in Acute Leukemia: Retrospective Natural Experiment
BACKGROUND: Electronic medical record (EMR) systems have been associated with better clinical workflows and fewer documentation errors. However, evidence regarding their effect on time-sensitive leukemia care in public hospitals in Latin America remains limited. OBJECTIVE: This study aimed to compare 60-day mortality and urgent supportive-care processes between 2 tertiary public hospitals in Mexico with different documentation models (integrated EMR vs traditional physical records [TPR]), under the hypothesis that digital workflows may facilitate more timely treatment. METHODS: We conducted a retrospective natural experiment including 274 patients with newly diagnosed acute leukemia treated between February 2023 and April 2025. Clinical characteristics, treatment intensity, complications during induction, antibiotic administration times, and survival outcomes were abstracted from finalized institutional records that are routinely reviewed at discharge by the institutional medical record committee as part of standard quality-assurance procedures. The primary outcome was 60-day mortality. Secondary outcomes included time to first antibiotic dose after recognition of febrile neutropenia, treatment-related complications, and the number of operational steps required for urgent care processes. A subgroup analysis of 70 patients with complete timing documentation was performed for antibiotic administration. Comparisons between hospitals were performed using univariate tests, Kaplan-Meier 60-day survival curves, and multivariable logistic regression. RESULTS: Of the 274 included patients, 104 (38%) were treated at the hospital using an integrated EMR, and 170 (62%) at the hospital using TPR. Sixty-day mortality was lower in the EMR hospital (6/104, 5.8%) than in the TPR hospital (61/170, 35.9%; P<.001). In the subgroup with complete timing data, the mean time from febrile episode recognition to first antibiotic administration was shorter in the hospital using EMR than in the hospital using TPR (54, SD 18.4 minutes; P<.001). Although the EMR hospital used a higher proportion of high-intensity regimens, patients in that hospital had better 60-day outcomes. In multivariable analysis, hospital type remained independently associated with 60-day mortality (odds ratio 0.11, 95% CI 0.05-0.26; P<.001), whereas kidney injury and hepatotoxicity were associated with worse outcomes. CONCLUSIONS: In this natural experiment, the hospital using an integrated EMR had a lower 60-day mortality and shorter time to antibiotic administration than the hospital using TPR. These findings are hypothesis-generating and suggest that digital workflows may contribute to more timely urgent supportive care, but they should be interpreted with caution, given the retrospective 2-center design and the potential for residual confounding.
19 Apr 2026
Read appraisal →Journal of global health
Associations between haemoglobin-to-red cell distribution width ratio and mortality in intracerebral haemorrhage: a population-based analysis of the MIMIC-IV database
BACKGROUND: Intracerebral haemorrhage (ICH) is a leading cause of mortality and morbidity worldwide. Identifying early prognostic biomarkers is crucial to optimise clinical management of critically ill patients with ICH. The haemoglobin-to-red cell distribution width ratio (HRR) has recently emerged as a potential predictor in various critical illnesses, but its role in ICH remains unclear. This study aimed to evaluate associations between HRR and mortality in patients with ICH. METHODS: This retrospective cohort study included the data of adults (≥18 years) extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (version 1). HRR was calculated from the first available haemoglobin and RDW measurements within one day of each other. Patients were categorised into HRR quartiles. The primary outcomes were 28-day and 1-year all-cause mortality. Associations were assessed using Cox proportional hazards models. RESULTS: The data of 1915 patients (mean age 67.5 years) were analysed retrospectively. After adjusting for possible confounders, compared with the lowest HRR quartile (Q1), patients in Q3 and Q4 had significantly lower 28-day mortality (Q3: adjusted hazard ratio (aHR) = 0.72; 95% CI = 0.54, 0.97; Q4: aHR = 0.67; 95% CI = 0.49, 0.90). Similarly, higher HRR quartiles were associated with reduced 1-year mortality risk (Q3: aHR = 0.64; 95% CI = 0.49, 0.84; Q4: aHR = 0.56; 95% CI = 0.42, 0.75). CONCLUSIONS: Lower HRR at admission is independently associated with higher short-term and long-term mortality in ICU patients with ICH. HRR may serve as a candidate prognostic biomarker for early risk stratification in this high-risk population. Further prospective studies are warranted to confirm these findings.
18 Apr 2026
Read appraisal →BMJ open
Association between ambient air pollution exposure levels and the risk of developing pulmonary embolism in the Chinese population: findings from the Chinese Cardiovascular Association (CCA) Database-Chest Pain Centre
OBJECTIVE: To analyse the associations between exposure to different air pollutants and the morbidity of pulmonary embolism (PE). DESIGN: Time series study with a distribution lag non-linear model. SETTING: 275 cities in China, 1 January 2015 to 31 March 2022. PARTICIPANTS: 27 369 cases of PE. MAIN OUTCOME MEASURES: The associations between exposure to different air pollutants and the morbidity of PE. RESULTS: During the study period, 27 369 cases of PE were recorded. PM2.5(Particulate Matter 2.5), PM10(Particulate Matter 10) and NO2(Nitrogen Dioxide) exposure levels were associated with an increased risk of developing PE in the single-pollutant model. PM2.5 exposure caused the greatest risk of developing PE at lag 1 in the single-day lag model, with a relative risk (RR) value of 1.033 (95% CI 1.007 to 1.058). PM10 and NO2 exposure had the greatest effects at lag 0, with RR values of 1.038 (95% CI 1.016 to 1.059) and 1.039 (95% CI 1.009 to 1.068), respectively. No associations were found between CO(Carbon Monoxide), O3(Ozone) or SO2(Sulfur Dioxide) exposure levels and the risk of developing PE. PM2.5, PM10 and NO2 exposure levels were most strongly associated with the development of PE at lag 01 in the cumulative lag model, with RR values of 1.052 (95% CI 1.009 to 1.095), 1.053 (95% CI 1.020 to 1.086) and 1.058 (95% CI 1.005 to 1.111), respectively. CONCLUSIONS: Short-term exposure to PM2.5, PM10 and NO2 can increase the risk of developing PE, especially in females. The effects of PM2.5 and PM10 exposure were more significant in cold seasons and in North China.
17 Apr 2026
Read appraisal →The New England journal of medicine
Ianalumab plus Eltrombopag in Immune Thrombocytopenia
BACKGROUND: Current second-line treatments for immune thrombocytopenia (ITP) require long-term administration. Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP. METHODS: In this phase 3, randomized, double-blind trial, we assigned, in a 1:1:1 ratio, adults with primary ITP and an insufficient response or a relapse after first-line glucocorticoid therapy to receive ianalumab at a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months. Eltrombopag, an oral thrombopoietin-receptor agonist, was administered once daily in each group according to local prescribing information; the dose was tapered until discontinuation by the end of week 24 in eligible patients. The primary end point was freedom from treatment failure, as determined in a time-to-event analysis, with treatment failure defined by a platelet count of less than 30×109 per liter more than 8 weeks after randomization, initiation of rescue therapy more than 8 weeks after randomization, initiation of new ITP therapy, inability to taper or discontinue eltrombopag because of an inadequate platelet count, or death from any cause, whichever occurred first. The key secondary end point was a stable response at 6 months, defined by a platelet count of at least 50×109 per liter in at least 75% of the measurements between weeks 19 and 25 without use of rescue therapy or new ITP therapy. Safety was assessed. RESULTS: A total of 152 patients underwent randomization: 50 to the 9-mg ianalumab group, 51 to the 3-mg ianalumab group, and 51 to the placebo group. The estimated probability of being free from treatment failure at 12 months was 54% (95% confidence interval [CI], 39 to 67) in the 9-mg group, 51% (95% CI, 36 to 64) in the 3-mg group, and 30% (95% CI, 18 to 43) in the placebo group. The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag; the estimated hazard ratio for treatment failure (ianalumab vs. placebo) was 0.55 (P = 0.04) in the 9-mg group and 0.58 (P = 0.045) in the 3-mg group. The percentage of patients with a stable response at 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P = 0.045). The overall frequency of adverse events during the treatment period was generally similar in the three groups. The frequency of serious adverse events was 16% in the 9-mg group, 6% in the 3-mg group, and 4% in the placebo group. CONCLUSIONS: Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag. (Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.).
16 Apr 2026
Read appraisal →Cancer immunology, immunotherapy : CII
Hematological toxicities and thrombosis risk associated with immune checkpoint inhibitors: a pharmacovigilance study from 2014 to 2024
BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in a wide range of cancers but may also induce hematological toxicities and thrombosis risk. This study comprehensively evaluated hematological and thrombotic adverse events (AEs) associated with ICIs in real-world settings using the FDA Adverse Event Reporting System (FAERS) database, aiming to characterize their clinical features. METHODS: Data were extracted from the FAERS database (Q1 2014 to Q4 2024) for disproportionality analysis. AEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA). Associations between ICIs and hematological/thrombotic AEs were assessed via the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods. Clinical characteristics of affected patients were analyzed, and time-to-onset across ICI regimens was further evaluated. RESULTS: We identified 14,753 ICI-associated hematological toxicities and thrombotic events. Among reports with available sex information, a higher reporting frequency was observed in men (50.90%) than in women (40.11%). The most frequent AEs were anemia (2963 cases, 16.62%), thrombocytopenia (1961, 11.00%), febrile neutropenia (1935, 10.85%), neutropenia (1392, 7.81%), myelosuppression (979, 5.49%), pancytopenia (739, 4.14%), lymphadenopathy (475, 2.66%), disseminated intravascular coagulation (DIC; 468, 2.62%), leukopenia (468, 2.62%), and deep vein thrombosis (DVT; 213, 1.19%). The median time-to-onset for ICI monotherapy-associated AEs was 28 days (IQR 11-79), with 78.22% occurring within 3 months. Notably, DIC and DVT had the highest mortality proportion among the top 10 AEs. CONCLUSION: Hematological and thrombotic AEs associated with ICI therapy show notable reporting frequencies in FAERS. Combination regimens demonstrated stronger reporting signals for certain events. These AEs frequently showed early reporting and notable mortality proportions, highlighting the importance of clinical vigilance. Further studies are needed to confirm these findings.
16 Apr 2026
Read appraisal →Cancer
A phase 1 study of ASTX727 plus talazoparib in patients with triple-negative or hormone resistant/HER2-negative metastatic breast cancer
BACKGROUND: Poly(adenosine diphosphate ribose) polymerase (PARP) is recruited to DNA damage sites along with epigenetic factors such as DNA methyltransferase 1 (DNMT1). Inhibitors of DNMT modulate reactive oxygen species (ROS)-cyclic adenosine monophosphate (cAMP)/Protein Kinase A signaling and induce a "BRCAness phenotype" that further sensitizes cells to PARPi. In preclinical studies, combined DNMTi + PARPi therapy was effective in both triple-negative (TNBC) and hormone resistant (HRBC) models with intact BRCA. METHODS: The authors conducted a phase 1 study combining the oral DNMTi ASTX727 with the PARPi talazoparib in patients with previously treated TNBC or HRBC. Patients with deleterious mutations of BRCA were excluded. A classical 3+3 design guided dose escalation/de-escalation, and 28 days constituted each cycle. Serial peripheral blood mononuclear cells (PBMCs) were analyzed for changes in methylation using the Infinium Methylation EPIC BeadChip and LINE1 sequencing. RESULTS: Thirty-four evaluable patients were enrolled and treated in eight dose cohorts. Myelosuppression was common with grade >3 neutropenia in 42% and grade 3 anemia and thrombocytopenia in 13%. Dose-limiting toxicity was limited to neutropenia. Efficacy was assessed in 29 patients. There were no objective responses, six patients had stable disease persisting for >4 months in three patients. LINE1 demethylation ranged from ∼2%-10% and immune-specific CpGs (methylation in immune cells) changed 1%-5% at day 15. Methylation changes were not dose-dependent. CONCLUSIONS: ASTX727 plus talazoparib produces significant myelosuppression without other adverse events. Modest methylation changes in PBMCs were detected. There were no objective responses, but some heavily pretreated patients had stable disease for >4 months despite the attenuated doses.
15 Apr 2026
Read appraisal →International immunopharmacology
Multicentre development and validation of a risk model integrating immunotherapy and coagulation biomarkers for thrombosis in autoimmune neurological disorders
PURPOSE: Patients with Autoimmune Neurological Disorders (ANDs) require routine immunomodulatory therapy, which inherently increases thrombosis risk. Despite this recognised association, reliable tools for thrombosis prediction remain limited, highlighting the need for accurate risk stratification to inform targeted prevention strategies. PATIENTS AND METHODS: This multicentre retrospective study developed a machine learning-based thrombosis risk prediction model using data from 786 patients with ANDs receiving immunomodulatory therapy. The model was trained on data from three centres and externally validated on an independent fourth centre, evaluating six algorithms based on the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and Brier score. Feature selection and Shapley Additive Explanations (SHAP) analysis were applied to ensure model interpretability. RESULTS: Among all algorithms tested, XGBoost (XGB) demonstrated the best performance. On the external validation set, the XGB model achieved an AUROC of 0.949, AUPRC of 0.544, and Brier score of 0.045, significantly outperforming the traditional Padua score. SHAP analysis identified the top three thrombotic risk factors: elevated D-dimer levels, prolonged immobilisation, and advanced age. The total doses of intravenous immunoglobulin and glucocorticoid were also confirmed as significant contributors. The model further enabled stratification into low-, intermediate-, and high-risk groups, offering a practical tool for individualised thromboprophylaxis. CONCLUSION: This study presents a high-performing, interpretable model for early thrombosis risk prediction in patients with ANDs, which facilitates timely clinical decision-making and targeted preventive strategies to reduce thromboembolic complications.
15 Apr 2026
Read appraisal →Blood advances
Targeting Aurora kinase A to prevent GVHD and relapse after myeloablative allogeneic hematopoietic cell transplantation
The success of posttransplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has driven efforts to optimize partner therapies that balance GVHD and relapse prevention. We report phase 1 dose-finding results of PTCy, sirolimus (SIR), and VIC-1911, a selective oral Aurora kinase A (AURKA) inhibitor, after myeloablative allogeneic hematopoietic cell transplantation (allo-HCT). Results from murine and in vitro studies informed the development of the novel drug combination. In the phase 1 trial, patients aged 18 to 60 years received myeloablative conditioning, followed by PTCy (50 mg/kg; days +3/+4), SIR (from day +5; target 8-12 ng/mL), and VIC-1911 (25, 50, or 75 mg twice daily; days +5 to +45). The primary end point was achieving <54% phosphorylated histone H3 serine 10 expression in CD4+ T cells by day +21. Preclinical models show that combining SIR with AURKA inhibition suppresses signaling downstream of CD28, enhancing GVHD prevention while leveraging the antileukemia activity of AURKA inhibition. In the phase 1 trial, the optimal VIC-1911 dose achieving target pathway inhibition without dose-limiting toxicities was 75 mg twice daily. Clinical outcomes included no grade 3 to 4 acute GVHD through day 180 (0%) and low rates of moderate/severe chronic GVHD (6%) and relapse (0%) through 1 year (5/16 received maintenance). The 1-year overall survival for this cohort was 94%. VIC-1911 at 75 mg twice daily, combined with PTCy and SIR, effectively suppressed AURKA activity, offering promising GVHD and relapse prevention with a favorable safety profile and promising early clinical outcomes. The trial was registered at www.clinicaltrials.gov as NCT05120570.
15 Apr 2026
Read appraisal →Blood advances
RNA interference therapy targeting coagulation factor XI: a first-in-human trial of RBD4059 (vortosiran)
Inhibiting coagulation factor XI (FXI) activity has emerged as a promising strategy to prevent intravascular thrombosis. Here, we describe the first-in-human trial with an N-acetylgalactosamine-conjugated small interfering RNA (siRNA), RBD4059, targeting FXI. In this phase 1 single ascending dose study (NCT05653037), healthy volunteers were randomized to receive either active drug or placebo (6 + 2), administered subcutaneously, in 4 consecutive dose cohorts ranging from 50 mg to 600 mg. The primary end point was safety and tolerability up to day 169 after dose. Secondary end points included pharmacokinetic and pharmacodynamic (PD) parameters. Single ascending doses of RBD4059 were well tolerated, and no apparent safety concerns were identified. RBD4059 was associated with a dose-dependent and durable suppression of FXI activity up to >90%. Modeling of the available PD data supports clinical dosing schemes of 3 to 6 months to achieve a robust antithrombotic effect. Altogether, these observations support further clinical development of RBD4059 to provide an siRNA-based therapeutic option targeting FXI for patients inadequately treated with or contraindicated for current available thrombosis prophylaxis. This trial was registered at www.clinicaltrials.gov as #NCT05653037.
15 Apr 2026
Read appraisal →Blood advances
Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi in R/R marginal zone lymphoma: phase 1/2 BRUIN study.
Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies with a remitting and relapsing course. For systemic disease, available first-line therapies include anti-CD20 antibody as monotherapy or in combination with chemotherapy (chemoimmunotherapy), with second-line options including covalent Bruton tyrosine kinase inhibitors (cBTKi). However, management of relapsed and refractory (R/R) MZL remains challenging. Pirtobrutinib, a highly selective, noncovalent BTKi has shown promising efficacy and tolerability in poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here, we report the safety and efficacy of pirtobrutinib in MZL from the phase 1/2 BRUIN study. Endpoints included investigator-assessed objective response rate (ORR) by Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Among 36 patients with R/R MZL (extranodal [n = 6]; nodal [n = 17]; splenic [n = 13]), median age was 68 years (range, 22-83) and median prior lines of therapy were 3 (range, 2-10). The ORR was 55.6% (95% confidence interval [CI], 38.1- 72.1), including 3 (8.3%) complete responses and 17 (47.2%) partial responses. Median DOR was 17.8 months (95% CI, 7.4 to nonestimable [NE]), and median PFS was 16.6 months (95% CI, 9.0-22.1). With median follow-up of 32.4 months (IQR, 28.0-41.3), median OS was NE (95% CI, 29.5-NE). The ORR for patients with prior cBTKi therapy was 53.8% (95% CI, 33.4-73.4). Pirtobrutinib was well tolerated with dose reductions in 4 patients (11.1%) and permanent discontinuation due to treatment emergent adverse events in 4 patients (11.1%). Pirtobrutinib showed promising efficacy and safety in patients with heavily pretreated R/R MZL, including prior cBTKi. This trial was registered at www.clinicaltrials.gov as #NCT03740529.
15 Apr 2026
Read appraisal →Blood advances
HCT Pre-App program: a telemedicine-based prehabilitation for allogeneic hematopoietic cell transplant candidates
Frailty has emerged as a key component of allo-HCT candidate assessment and is closely associated with transplant outcomes. Exercise-based prehabilitation may improve transplant candidacy, yet real-world implementation is limited. Our institution implemented a structured Frailty Program (FP) to assess frailty and introduce prehabilitation interventions. This study describes the program's evolution and evaluates the impact of prehabilitation. Between April 2021 and April 2025, 185 consecutive allo-HCT candidates were included in 3 sequential FP phases. In the first phase (No-Prehab, n = 76), patients underwent frailty assessment only. In the second phase (Pilot-Prehab, n = 59), patients received a home-based, nonsupervised prehabilitation program. In the third phase (Tele-Prehab, n = 50), patients participated in the HCT Pre-App Program, a structured digital telemedicine intervention supervised by rehabilitation physicians. Frailty was assessed at first consultation and HCT admission using the HCT Frailty Scale. Median prehabilitation duration was 6 weeks. Adherence was high across frailty groups (76%-88%), with no adverse events. Prehabilitation improved frailty status: fit patients increased from 22% to 42% in the Pilot-Prehab cohort (P = .009) and from 34% to 56% in the Tele-Prehab cohort (P = .001). Tele-Prehab independently increased the odds of being fit at admission (odds ratio [OR], 3.86; P = .001) and reduced frailty incidence (OR, 0.17; P = .031). One-year OS and NRM were comparable across cohorts (OS, 74.5%, 84.5%, and 78.1%; P = .367) with a trend toward lower NRM among prehabilitated patients (NRM, 14.6%, 5.1%, and 5.6%; P = .075). Frailty is dynamic in allo-HCT candidates, and results support how home-based digital prehabilitation improves fitness before transplantation.
15 Apr 2026
Read appraisal →Blood advances
Zamtocabtagene autoleucel in relapsed/refractory B-NHL: 5-year follow-up of a CD20/19 tandem CAR T-cell phase 1 trial
Emerging long-term data indicate relapse rates of >50% after CD19-redirected chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). To reduce selective pressure on the CD19 antigen, we conducted a first-in-human phase 1 clinical trial of zamtocabtagene autoleucel (zamto-cel), a noncryopreserved tandem CD20-CD19-directed CAR T-cell therapy. Two predefined dose levels (dose level 1 [DL1], 1 × 106 and DL2, 2.5 × 106 CAR+ T cells per kg bodyweight) were applied. The primary end point (EP) was the maximum tolerated dose (MTD). Secondary EPs included adverse events, best overall response (BOR), and biomarker assessments. A total of 12 patients, 6 patients per DL, were treated. No dose-limiting toxicity and no cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome of grade ≥3 were observed. Thus, MTD was not reached. The BOR by investigator assessment was 75%, with 5 of 12 patients (42%) achieving complete remission (CR) until month 12 with no relapse in clinical evaluation up to 5 years after infusion. CR was associated with a higher mean maximum observed concentration of zamto-cel and detection of zamto-cel beyond month 6. Additional product characterization revealed increased expression of CD27 and CD127 along with increased expansion of CAR+ central memory T cells in patients with CR, facilitating persistence and improved outcomes in R/R B-NHL treated with zamto-cel. Based on the promising risk-to-benefit ratio, evaluation of zamto-cel at DL2 is ongoing in pivotal phase 2 clinical trials for patients with R/R aggressive B-NHL. This trial was registered at www.ClinicalTrials.gov as NCT03870945.
15 Apr 2026
Read appraisal →Blood advances
Treatment and survival outcomes for patients with follicular lymphoma and POD24: a systematic review and meta-analysis
Follicular lymphoma with progression of disease within 24 months (POD24) is associated with poor prognosis and represents clinical challenges. Therefore, we performed a systematic review and pooled analysis of patients with POD24. Twenty-one trials involving 1242 participants were included, assessing the overall response rate (ORR), complete response (CR), duration of response, and progression-free survival. In some trials, we compared pooled response rates between POD24 and non-POD24 populations with the same treatment regimen. Four trials evaluated chimeric antigen receptor (CAR) T-cell therapy in patients with POD24. Pooled analysis showed an ORR of 91.2% (95% confidence interval [CI], 83.7-98.7) with significant heterogeneity (P = .0414; I2 = 68.61%) and a CR of 75.7% (95% CI, 55.1-96.4) with significant heterogeneity (P< .0001; I2 = 93.99%). The specific response rates for different bispecific antibodies in POD24 were pooled analysis, the ORR was 81.6% (95% CI, 75.9-87.3) with no heterogeneity (P = .6958; I2 = 0%), and the CR was 65.7% (95% CI, 57.1-74.3) with moderate heterogeneity (P = .2148; I2 = 34.99%). For anti-CD19 antibody-drug conjugates (ADCs)/monoclonal antibodies (mAbs), the ORR and CR rate for loncastuximab plus rituximab and tafasitamab plus R2 (lenalidomide + rituximab) were 100% and 79.3%, and 87.5% and 43.2%, respectively. Phosphatidylinositol 3-kinase inhibitors and anti-CD20 mAb-containing regimens were also analyzed in pooled analyses. Our results demonstrated that anti-CD19 CAR T-cell therapy achieved the highest CR rate. Additionally, bispecific antibodies, anti-CD19 ADCs/mAbs, and the combination of lenalidomide with obinutuzumab or rituximab also exhibited excellent efficacy. Notably, lenalidomide plus obinutuzumab showed superior efficacy compared with R2.
15 Apr 2026
Read appraisal →Blood advances
Neutrophil CD14 is a driver and a therapeutic target for deep vein thrombosis.
Neutrophil-mediated persistent inflammation and neutrophil extracellular trap formation (NETosis) are critical in the pathogenesis of deep vein thrombosis (DVT). Identifying the mechanisms controlling these proinflammatory and prothrombotic functions is critical for designing and developing new therapeutics for DVT. However, how neutrophils acquire these phenotypes during the early stages of DVT remains poorly understood. Here, multiomic analyses (RNA sequencing, proteomics, and flow cytometry) of bone-marrow neutrophils 3 hours after DVT, revealed consistent overexpression of CD14. Concurrently, mice with DVT exhibited significantly elevated plasma granulocyte colony-stimulating factor (G-CSF) and neutrophil hyperactivation. Mechanistic studies using a geometric deep learning model (DeepPBS) and chromatin immunoprecipitation revealed that elevated G-CSF drives CD14 overexpression by upregulating the transcription factor C/EBPα (leucine zipper CCAAT-enhancer binding protein α). Importantly, neutrophil-specific CD14 knockdown using a novel lentiviral short hairpin RNA approach significantly improved DVT outcomes by lowering thrombus burden, thrombosis incidence, and intrathrombus neutrophil and citrullinated histone H3 accumulation. Studies in G-CSF stimulated primary human neutrophils revealed that CD14 inhibition reduces markers of inflammation and NETosis (activated gasdermin D, citrullinated histone H3, and S100A8/A9), while increasing apoptosis, thus demonstrating translational relevance. Collectively, our study uncovers an essential role of neutrophil CD14 in DVT pathogenesis and establishes it as a promising therapeutic target for DVT.
14 Apr 2026
Read appraisal →Blood advances
How to determine the optimal duration of anticoagulation for VTE: an evidence-based decision-analytical approach
When advising patients on the optimal duration of anticoagulation for venous thromboembolism (VTE), current management often relies on the intuition of treating physicians and guideline panels, an approach that remains opaque to outside observers. We present a decision-analytical framework adopted in our practice. This approach formalizes the intuition of physicians and guideline panels, providing an explicit and transparent integration of the best available evidence on benefits and harms. It also incorporates a systematic method for eliciting patient values and preferences to determine the optimal duration of anticoagulation. To demonstrate the practical utility of the decision-analytical approach, we apply it to 3 clinical scenarios: unprovoked VTE, VTE related to long-haul travel, and portal vein thrombosis in cirrhosis. By transparently synthesizing evidence and patient values, this method supports individualized, evidence-based, patient-centered recommendations for the duration of anticoagulation, and it is applicable to solving similar clinical problems in hematology and medicine.
14 Apr 2026
Read appraisal →Blood advances
MPN-FIT: a randomized controlled pilot trial of supervised exercise in myeloproliferative neoplasms
Myeloproliferative neoplasms (MPN) are associated with a high symptom burden and impaired quality of life (QoL), often unaided by available treatments. Physical activity has demonstrated benefits in other cancers; however, its potential has yet to be explored in MPN. This randomized controlled trial aimed to evaluate the feasibility, acceptability, and efficacy of a supervised exercise program for patients with MPN based on longitudinal assessment of symptom burden, QoL, and clinical/inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, ferritin, lactate dehydrogenase [LDH], and serum cytokines). Patients with MPN (n = 55) were randomized 3:2 to a 12-week home-based exercise intervention (flexibility/resistance/aerobics) supervised by a kinesiologist vs waitlist control. Measures included patient-reported outcome questionnaires, peripheral blood sampling, and postintervention interviews with participants. Forty-seven patients completed the trial (FIT group, n = 26; control group, n = 21). Median age was 66 years (range, 27-86), and 60% were female. All feasibility benchmarks were met, with 88% of participants satisfied and 92% with intent to continue an exercise program on a regular basis. A significant reduction in LDH was observed in FIT patients compared with controls (-14.5 U/L vs +4.0 U/L; P = .03). Patients interviewed described positive effects of the intervention on symptoms and would unanimously recommend the program to others with MPN. In this pilot study, supervised exercise was feasible, acceptable, and showed potential benefits on inflammatory/disease markers.
14 Apr 2026
Read appraisal →Lancet (London, England)
Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention: 10-year follow-up of the HOST-EXAM trial
BACKGROUND: The long-term clinical outcomes of clopidogrel monotherapy versus aspirin monotherapy after percutaneous coronary intervention (PCI) remain uncertain. We conducted a 10-year follow-up of the HOST-EXAM trial to assess the very long-term effects of clopidogrel versus aspirin monotherapy in this setting. METHODS: In HOST-EXAM, patients who had completed dual antiplatelet therapy without clinical events for 6-18 months after PCI were randomly assigned to receive clopidogrel 75 mg once daily or aspirin 100 mg once daily. This study is an investigator-initiated 10-year extended follow-up of the HOST-EXAM trial. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium type ≥3 bleeding. The primary analysis was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov (NCT02044250) and is complete. FINDINGS: From March 26, 2014, to May 29, 2018, 5530 patients were enrolled and 5438 were randomly assigned to the aspirin group (n=2728) or the clopidogrel group (n=2710). Clinical follow-up status was ascertained on May 1, 2025, resulting in a median follow-up duration of 10·5 years (IQR 9·4-11·4) after PCI and a completion rate of 92·8%. Clopidogrel was associated with a lower rate of the primary composite endpoint than aspirin (Kaplan-Meier estimate 25·4% for the clopidogrel group vs 28·5% for the aspirin group; hazard ratio 0·86 [95% CI 0·77-0·96]; log-rank p=0·0050). Clopidogrel was also associated with a lower rate of the thrombotic endpoint (17·3% vs 20·0%; log-rank p=0·0024) and bleeding endpoint (9·1% vs 10·8%; log-rank p=0·020). All-cause mortality was similar between groups. INTERPRETATION: During 10 years of follow-up, clopidogrel monotherapy, compared with aspirin monotherapy, was associated with lower rates of the primary composite, ischaemic, and bleeding outcomes, but not all-cause mortality after PCI. These findings support consideration of clopidogrel as an alternative to aspirin for long-term antiplatelet monotherapy during the chronic maintenance phase after PCI. FUNDING: Ministry of Health & Welfare, South Korea.
14 Apr 2026
Read appraisal →Medicine
Association of blood urea nitrogen to serum albumin ratio with mortality in ICU patients with sepsis-induced coagulopathy: A Retrospective Cohort Study from MIMIC-IV database
The blood urea nitrogen to serum albumin ratio (BAR) has shown promise as a prognostic marker in sepsis, yet its specific role in sepsis-induced coagulopathy (SIC) remains unclear. We aimed to clarify whether BAR informs mortality risk in critically ill intensive care unit (ICU) patients with SIC. Using the Medical Information Mart for Intensive Care IV database, we identified consecutive ICU patients admitted between 2008 and 2022 who fulfilled Sepsis-3 criteria and had an SIC score ≥4. BAR was calculated from the 1st available laboratory values. Multivariable Cox regression and restricted cubic splines were used to estimate mortality associations after adjustment for demographics, comorbidities, interventions, severity scores (Sequential Organ Failure Assessment, Simplified Acute Physiology Score II), and laboratory parameters. The primary end-point was 30-day mortality; 90- and 365-day mortality were secondary. Among 4244 patients, higher admission BAR independently predicted increased mortality at 30, 90, and 365 days. Each 10-unit rise in BAR conferred a 30% higher hazard of death within 30 days (unadjusted hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.25-1.35; P < .001). After full adjustment, the association persisted (HR 1.18, 95% CI 1.12-1.24; P < .001). Similar patterns were seen for longer-term outcomes. A clear dose-response relationship was observed across BAR tertiles; patients in the highest tertile (BAR ≥ 10 mg/g) had markedly higher mortality risk (adjusted HR 1.69, 95% CI 1.43-2.00; P < .001) than those in the lowest. Nonlinear analysis revealed a curvilinear BAR-mortality relationship, and subgroup analyses showed consistent findings, with significant effect modification by age. In critically ill patients with SIC, an elevated admission BAR independently predicts short- and long-term mortality and may aid risk stratification and early intervention planning.
12 Apr 2026
Read appraisal →Cancer immunology, immunotherapy : CII
A phase I, single-arm, open-label, dose-escalation, multicenter study of SAR445419, an off-the-shelf, ex vivo expanded allogeneic natural killer cell product, in participants with relapsed or refractory acute myeloid leukemia
BACKGROUND: SAR445419 is an investigational, off-the-shelf, allogeneic NK cell therapy derived from donor peripheral blood mononuclear cells and expanded ex vivo using PM21 particles. METHODS: This multicenter, Phase 1, dose-escalation study (NCT05712278) evaluated optimal dose(s), safety, and tolerability of SAR445419 in adults (aged ≥ 18 years) with relapsed/refractory acute myeloid leukemia (R/R AML). Following lymphodepleting chemotherapy (fludarabine 30 mg/m2/day and cytarabine 2 g/m2/day for 5 days), participants received six intravenous SAR445419 (1 × 109 and 3 × 109 NK cells/dose) doses, starting with the lower dose. The primary endpoint was the incidence of dose-limiting toxicities (DLTs), and key secondary endpoints included adverse events (AEs), hematological recovery, hematopoietic stem cell transplantation, and response rate. RESULTS: Of the 12 planned participants, 7 patients were enrolled, of whom 6 received SAR445419 before sponsor decided early study termination for reasons unrelated to safety or efficacy. No DLTs were observed. All participants experienced treatment-emergent adverse events (TEAEs); six had grade ≥ 3 TEAEs; and four had serious adverse events (SAEs). Two SAR445419-related SAEs (infusion-related reactions: both grade 2) were managed with supportive care. All participants experienced grade 3 anemia and grade 4 thrombocytopenia and neutropenia. Five deaths were reported, all due to disease progression, none related to SAR445419. No clinical responses were observed. CONCLUSIONS: This study demonstrated the overall safety of off-the-shelf ex vivo expanded allogeneic NK cells in patients with R/R AML. The successful manufacturing and distribution support the feasibility of donor-derived off-the-shelf NK cells in a clinical setting. Further investigations are required to improve the clinical efficiency of NK cells.
12 Apr 2026
Read appraisal →Journal for immunotherapy of cancer
Anti-TIM-3 antibody TQB2618 in combination with penpulimab in relapsed or refractory classic Hodgkin lymphoma previously treated with PD-1/PD-L1 therapy: a multicenter, open-label, single-arm, phase Ib clinical trial
BACKGROUND: Immune checkpoint inhibitors achieve high response rates in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL), but few treatment options are available for patients who experience failure after PD-1/PD-L1 blockade. T cell immunoglobulin and mucin-domain containing-3, a key mediator of immune escape from PD-1/PD-L1 inhibition, is targeted by TQB2618, a humanized IgG4 monoclonal antibody. This phase Ib study aimed to evaluate the safety and efficacy of TQB2618 in combination with the anti-PD-1 antibody penpulimab in patients with r/r cHL. METHODS: This multicenter phase 1b study was conducted from June 2022 to September 2024 at 12 sites in China (NCT05400876). The study included a dose-escalation phase in which patients with r/r lymphoma received TQB2618 (600 or 1200 mg, every 3 weeks, Q3W) plus penpulimab (200 mg, Q3W) to evaluate dose-limiting toxicities and determine the recommended phase II dose (RP2D). The subsequent dose-expansion phase enrolled patients with r/r cHL previously treated with PD-1/PD-L1 inhibitors to assess the objective response rate (ORR). RESULTS: 10 patients with r/r lymphoma were enrolled in the dose-escalation phase, and TQB2618 (600 mg, Q3W) plus penpulimab (200 mg, Q3W) was selected as the RP2D. In the dose-expansion phase, 18 additional patients with r/r cHL previously treated with PD-1/PD-L1 inhibitors were enrolled. Among the total 21 r/r cHL patients, the median age was 32 years (range, 22-65), and 12 (57%) were male. The ORR was 52%, including 1 complete response and 10 partial responses. Treatment-related adverse events (TRAEs) occurred in 18 patients (86%), with grade ≥3 TRAEs in 5 (24%). The most common TRAEs (≥20%) were platelet count decreased (24%), anemia (24%), and aspartate aminotransferase increased (24%). As of the data cut-off in December 2024, the median follow-up was 14.1 months, the median duration of response and the median overall survival had not yet been reached. CONCLUSIONS: TQB2618 in combination with penpulimab was well tolerated and demonstrated promising efficacy in patients with cHL who had failed prior anti-PD-1/PD-L1 therapy, supporting its potential as a therapeutic option for this difficult-to-treat population. TRIAL REGISTRATION NUMBER: NCT05400876.
12 Apr 2026
Read appraisal →Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Phase II Study of BCMA Chimeric Antigen Receptor T-Cell Therapy in Patients With Newly Diagnosed Multiple Myeloma Ineligible for or Not Proceeding to Autologous Stem-Cell Transplantation (CAREMM-001)
PURPOSE: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for or not proceeding to autologous stem-cell transplantation (ASCT)-often because of age or frailty-have limited opportunities to receive multiple effective lines of therapy, underscoring the need for novel frontline strategies. METHODS: In this phase II, open-label, single-arm trial (ClinicalTrials.gov identifier: NCT05860036), patients received 3-4 cycles of protocol-allowed induction, followed by B-cell maturation antigen (BCMA) CAR-T infusion, and subsequent consolidation and lenalidomide maintenance. The primary end point was the rate of minimal residual disease (MRD) negativity (10-5) at Month three postinfusion. RESULTS: Between April 4, 2023, and December 26, 2024, 43 patients were screened, 40 were enrolled, and 36 received infusion (median age, 68 years [46-75]). In the infused cohort, the MRD negativity rate at Month three postinfusion was 100% (36 of 36; 95% CI, 90.3 to 100.0). With a median follow-up of 15.8 months postinfusion (range, 4.3-26.0), no MRD recurrence was observed. The complete response rate (CRR) increased from 33.3% (12 of 36; 95% CI, 18.6 to 51.0) preinfusion to 69.4% (25 of 36; 95% CI, 51.9 to 83.7) at Month 3% and 94.4% (34 of 36; 95% CI, 81.3 to 99.3) at last follow-up. The most common grade 3 to 4 adverse events were transient cytopenia, including lymphopenia (100%), neutropenia (88.9%), leukopenia (80.6%), thrombocytopenia (19.4%), and anemia (8.3%). Cytokine release syndrome occurred in 52.8% of patients (all grade 1 to 2), immune effector cell-associated neurotoxicity in 5.6% (all grade 1), and infections in 30.6% (grade ≥3 in 19.4%). No deaths or disease progressions occurred by cutoff. CONCLUSION: Frontline BCMA CAR-T therapy induces deep, rapid, and durable remissions with a manageable safety profile in the NDMM population ineligible for or not proceeding to ASCT. These findings support its investigation as a potentially practice-changing strategy for this population.
11 Apr 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
A trifold prehabilitation model prior to induction chemotherapy in patients with leukemia: a randomized controlled trial
PURPOSE: A trifold prehabilitation program that integrates exercise, nutritional support, and psychological care has not yet been incorporated into routine care for leukemia patients prior to induction chemotherapy. This study aimed to evaluate the safety and feasibility of this trifold intervention and to further examine its potential impact on physical fitness, nutritional risk, and psychological health. METHODS: In a single-blind, parallel-group randomized trial, 86 newly diagnosed leukemia patients at a tertiary hospital in China were randomly assigned to a 12-week prehabilitation group (n = 43) or usual care (n = 43). Primary outcomes were recruitment, attrition, and safety. Secondary outcomes included the 6-min walk test (6MWT), exercise self-efficacy, cancer-related fatigue (CRF), anxiety, depression, and nutrition. Assessments occurred at baseline (T0), pre-chemotherapy (T1), and 1 (T2) and 3 months (T3) post-chemotherapy. RESULTS: The recruitment rate was 60.14%, with an attrition rate of 20.93%, and no serious adverse events occurred. Compared with controls, the intervention group showed significantly greater improvements in 6-min walk distance and cancer-related fatigue from T1 to T3 (all p < 0.05). Improvements in exercise self-efficacy were significant at T2 and T3 but not at T1. Nutritional status improved at T3 (p = 0.033). Anxiety and depression levels were consistently lower across all follow-up points (p < 0.01). CONCLUSIONS: This study demonstrates that prehabilitation is safe, feasible, and potentially beneficial for physical, nutritional, and psychological outcomes in leukemia patients. TRIAL REGISTRATION: China Clinical Trials Registration Platform: ChiCTR2500105061, date of registration: June 27, 2025 (retrospectively registered).
10 Apr 2026
Read appraisal →JMIR mHealth and uHealth
Effectiveness of mHealth-Based Nutritional Interventions on Iron Status of Pregnant Women: Systematic Review of Randomized Controlled Trials
BACKGROUND: Anemia is a global health concern. It is disproportionately prevalent among pregnant women in low-resource regions, where iron deficiency is the leading cause. Given the multifactorial nature of anemia, a range of nutritional interventions is recommended. However, effective implementation is often hindered by limited health care access, poor adherence to supplementation, and gaps in nutrition knowledge and counseling. To address these challenges and optimize hemoglobin (Hb) levels among pregnant women, mobile health (mHealth)-based nutritional interventions offer a promising alternative. OBJECTIVE: The aim of the study is to review available evidence on the effectiveness of mHealth-based nutritional interventions on iron status (Hb and/or serum ferritin concentration) among pregnant women. METHODS: Searches were conducted in Embase, CINAHL, Cochrane Library, PubMed, Web of Science, and Scopus, and supplemented by snowballing to identify additional relevant studies from citation lists. The key search strings comprised 4 concepts: "mobile health," "nutritional intervention," "Hb, anemia or iron deficiency anemia," and "pregnant women." Predefined inclusion and exclusion criteria were applied during screening. The methodological quality of included studies was assessed using the Risk of Bias 2 tool. The primary end point was the change in mean Hb concentration or serum ferritin level. Effect sizes (ESs) were calculated as standardized mean differences, including Cohen d and Hedges g. RESULTS: Of the 14,284 studies identified, only 11 randomized controlled trials were included. These studies used various modes of delivery, including mobile phone calls (n=1), SMS text messaging (n=3), and mobile apps (n=4), with some using more than 2 modes (n=3). The effect of mHealth-based nutritional interventions on iron status varied significantly. In total, 4 studies demonstrated a large ES (>0.8), with 3 relying on WhatsApp Messenger as an mHealth delivery mode. Approximately 82% (9/11) of the included studies reported a positive effect (P values ranging from <.001 to .047) of the intervention on Hb level, whereas 2 studies reported no statistically significant association (P=.33 and P=.35, respectively). Notably, interventions with the largest ES achieved clinically significant improvements in Hb concentration, with within- and between-group differences exceeding 1 g/dL. However, including behavioral change theories and nutrition-sensitive components was not consistently associated with larger ESs. Due to high heterogeneity (I2>95%), attributed to variations in mHealth delivery modes, functions, and interactive features across the included studies, meta-analysis could not be performed. CONCLUSIONS: This review demonstrates that mHealth-supported nutritional interventions effectively optimize Hb concentration in pregnant women. While SMS text messaging was less effective in improving Hb concentration, combining it with another mHealth delivery mode, such as phone calls, improved intervention effectiveness. However, the variability in mHealth delivery modes, functions, and interactive features underscores the need for tailored strategies that account for context-specific challenges, digital literacy, and access to technology to enhance effectiveness.
10 Apr 2026
Read appraisal →Blood
A decade of ibrutinib for CLL with and without TP53 aberration: final report on an investigator-sponsored phase 2 study
Bruton tyrosine kinase inhibitors improve outcomes for patients with chronic lymphocytic leukemia (CLL). Long-term data with continuous therapy are limited. With a median follow-up of 10.0 years, we report final results on 84 patients with TP53 aberrations (deletion of chromosomal arm 17p or TP53 mutation) or ≥65 years of age treated with 420 mg of single-agent ibrutinib daily until progression or unacceptable toxicity. A total of 52 (61.9%) patients were previously untreated; 56 (66.7%) had unmutated immunoglobulin heavy-chain variable region; and 53 (63.1%) had TP53 aberrations, including 34 treatment naïve patients. As of 31July 2024, 9 (10.7%) patients continued ibrutinib, 39 (46.4%) discontinued ibrutinib for progressive disease, 31 (36.9%) for adverse events, and 5 (5.9%) withdrew consent. The median progression-free survival (PFS) was 7.2 years; median overall survival (OS) was not reached. In patients with and without TP53 aberrations, median PFS was 5.6 years and not reached, and 10-year OS was 51.3% and 75.3%, respectively. The estimated 10-year PFS and OS for patients with TP53-aberrant CLL treated in first line was 38.6% and 65.7%, respectively. Minimal residual disease (MRD) was quantified by peripheral blood flow cytometry annually. Undetectable MRD (uMRD; at 10-4) was achieved in 13 (15.5%) patients after a median of 5 years. Twelve patients maintained uMRD, the longest observation ongoing at 8.0 years. Seventeen (42.5%) patients with best response of high MRD (>10-2) remained progression-free for >5 years. These results highlight durable benefits and deepening responses with ibrutinib, including in high-risk CLL. Whether patients maintaining uMRD for years can safely discontinue therapy should be assessed prospectively. This trial was registered at www.clinicaltrials.gov as NCT01500733.
10 Apr 2026
Read appraisal →Blood
A phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia
Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT. We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multikinase inhibitor dasatinib in adult patients with CBF-AML. Patients received "3+7" induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg daily on days 8 to 21 in induction, and on days 6 to 28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg daily. Primary end point was event-free survival (EFS). Secondary end points included overall survival, relapse-free survival, and cumulative incidence of relapse. A total of 202 patients were randomly assigned to the standard arm (n = 102) and to the dasatinib arm (n = 100). Median age was 49 years (range, 18-77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); and 58 (28.7%) patients had a KIT comutation. There was no statistically significant difference in EFS (hazard ratio, 0.92; 95% confidence interval, 0.63-1.33; P = .66) or secondary end points between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%). In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.ClinicalTrials.gov as NCT02013648.
10 Apr 2026
Read appraisal →Lupus science & medicine
Unsupervised clustering of clinical and laboratory features of systemic lupus erythematosus: insights from a multicentre cohort
OBJECTIVE: This study explored the relationship between clinical phenotypes and immuno-molecular features of systemic lupus erythematosus (SLE) using unsupervised machine learning and multi-omics integration. METHODS: A multicentre cohort of 1065 SLE patients from five teaching hospitals was studied. Unsupervised clustering was performed using integrated clinical and laboratory data to identify distinct phenotypic clusters. Multi-omics profiling, including proteomics and transcriptomics, was conducted for each cluster, comparing with healthy controls. In addition, 899 patients were prospectively followed for over 1 year to assess therapeutic responses and remission outcomes. RESULTS: Unsupervised clustering identified five distinct clusters of SLE based on clinical phenotypes and immunological signatures, and an intrinsic association was found between each cluster and immune-inflammatory features. Cluster 1 (renal; 14.27%) had predominant renal involvement (87.5%) and high disease activity. Cluster 2 (mucocutaneous; 39.53%) exhibited mainly cutaneous manifestations (72.45%) with mild visceral involvement and the highest rates of achieving low disease activity state (46.42%). Cluster 3 (neuropsychiatric; 14.74%) had a high frequency of neuropsychiatric manifestations (96.18%) and anti-U1 ribonucleoprotein antibodies positivity (42.04%). Cluster 4 (haematologic; 22.63%) was characterised by haematologic involvement, predominantly cytopenia (95.85%), with frequent antiphospholipid antibody positivity and direct Coombs positivity (87.55%). Cluster 5 (cardiopulmonary; 8.83%) exhibited prominent cardiopulmonary involvement (97.87%) and serositis, with enrichment of inflammatory CD161+ regulatory T cells. Transcriptomic and proteomic analyses confirmed distinct molecular signatures and cluster-specific enrichment of biological pathways. Key molecule apolipoprotein A4 was validated using enzyme-linked immunosorbent assay. Regarding therapeutic outcomes at 1 year follow-up, Cluster 2 had the highest proportions achieving lupus low disease activity state (46.42%) and tapering glucocorticoids. Cyclophosphamide use was associated with greater clinical improvement (r=0.284; p=0.023) in Cluster 3, while in Cluster 5, rituximab use was associated with favourable responses (r=0.286; p=0.019). CONCLUSIONS: We identified five SLE clusters with distinct clinical, immunological features and treatment outcomes, demonstrating an intrinsic link between clinical involvement and immune-inflammatory alterations.
9 Apr 2026
Read appraisal →The New England journal of medicine
A Phase 2 Randomized Trial of Mezagitamab in Primary Immune Thrombocytopenia
BACKGROUND: Immune thrombocytopenia (ITP) is a disorder of increased platelet destruction and reduced platelet production and is associated with an increased bleeding risk and a compromised quality of life. Available therapies are ineffective in at least 20% of cases. Mezagitamab is an anti-CD38 antibody that targets plasma cells, plasmablasts, and natural killer cells. METHODS: We conducted this multicenter, double-blind, randomized, placebo-controlled trial to assess the safety and efficacy of mezagitamab at a dose of 100 mg, 300 mg, or 600 mg, as compared with placebo, administered subcutaneously once weekly for 8 weeks in adults with persistent or chronic ITP (mean platelet count on ≥2 measurements, <30,000 per microliter). The primary end point was adverse events. A key secondary efficacy end point was a platelet response (defined by a platelet count of ≥50,000 per microliter and ≥20,000 per microliter above the baseline value) on at least two visits at any time through week 16. RESULTS: In the combined mezagitamab groups (28 participants), the mean age was 50 years (range, 24 to 88) and the mean number of previous ITP therapies was 4 (range, 1 to 9); in the combined placebo groups (13 participants), the mean age was 39 years (range, 20 to 65) and the mean number of previous ITP therapies was 4 (range, 1 to 13). The mean baseline platelet count was 19,100 and 17,300 per microliter, respectively. Adverse events were reported in 19 of 28 participants (68%) in the combined mezagitamab groups and in 9 of 13 participants (69%) in the combined placebo groups; adverse events of grade 3 or higher in 5 of 28 participants (18%) and in 3 of 13 participants (23%), respectively; and serious adverse events in 4 of 28 participants (14%) and in 1 of 13 participants (8%). Through week 16, a platelet response was observed in 10 of 11 participants (91%) in the mezagitamab 600-mg group and in 3 of 13 participants (23%) in the combined placebo groups. CONCLUSIONS: Treatment with mezagitamab led to increased platelet counts, with a safety profile that appeared to be similar to that of placebo among participants with persistent or chronic ITP. (Funded by Takeda Development Center Americas; ClinicalTrials.gov number, NCT04278924.).
9 Apr 2026
Read appraisal →Journal of the American Heart Association
Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy
BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin. METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for biomarkers collected at baseline, week 2, or month 6. Participants were randomized to apixaban (n=123) or standard of care (VKA or low-molecular-weight heparin; n=59). Subgroup analyses accounted for prior VKA exposure. RESULTS: d-dimer levels decreased at month 6 in all treatment groups and remained stable during VKA-to-apixaban bridging. Apixaban significantly prolonged thrombin generation assay lag time and time to peak compared with VKAs and decreased peak thrombin similarly to VKAs in anticoagulant-naïve participants. Apixaban was associated with decreased fibrinogen and factor VIII at month 6, with no effect on protein C or S. Prior VKA exposure produced carryover effects, suppressing baseline d-dimer, thrombin generation assay parameters, and proteins C and S. CONCLUSIONS: Apixaban reduced hypercoagulability, as shown by decreased d-dimer levels and prolonged lag time, and preserved endogenous thrombin potential in thrombin generation assay, changes consistent with adult data. These findings align with SAXOPHONE's primary outcomes, supporting apixaban's favorable risk-benefit profile as a thromboprophylaxis option in children with heart disease.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
Impact of Atrial Fibrillation Pattern on Edoxaban Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease: A Secondary Analysis of the EPIC-CAD Randomized Clinical Trial
BACKGROUND: Paroxysmal atrial fibrillation (AF) is associated with a risk of stroke or systemic embolism similar to nonparoxysmal (persistent or permanent) AF. However, whether the optimal antithrombotic strategy in patients with AF and stable coronary artery disease differs by AF pattern remains uncertain. METHODS: This prespecified substudy of the EPIC-CAD (Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease) trial compared edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with AF and stable coronary artery disease. Stratified analyses were performed by AF pattern. The primary outcome was net adverse clinical events, defined as a composite of all-cause death, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, major bleeding, or clinically relevant nonmajor bleeding within 12 months. RESULTS: Among 1040 patients, 575 (55.3%) had paroxysmal and 465 (44.7%) had nonparoxysmal AF. The 12-month primary outcome rate was similar between paroxysmal and nonparoxysmal AF (10.3% versus 12.2%; adjusted hazard ratio [HR], 1.15 [95% CI, 0.79-1.68]). Edoxaban monotherapy was associated with a significantly lower risk of the primary outcome than dual antithrombotic therapy in both paroxysmal AF (4.6% versus 16.2%; adjusted HR, 0.23 [95% CI, 0.12-0.42]) and nonparoxysmal AF (9.3% versus 15.0%; adjusted HR, 0.56 [95% CI, 0.32-0.87]). No significant interaction was observed between antithrombotic strategy and AF pattern (P for interaction=0.10). CONCLUSIONS: In patients with AF and stable coronary artery disease, edoxaban monotherapy significantly reduced net adverse clinical events at 12 months compared with dual antithrombotic therapy, irrespective of AF pattern. REGISTRATION: URL: https://www.ClinicalTrials.gov; Unique identifier: NCT03718559.
8 Apr 2026
Read appraisal →Journal of the American Heart Association
Development and Validation of a Machine Learning Model to Predict Oral Anticoagulant Use in Stroke From Prothrombin Time-International Normalized Ratio and Activated Partial Thromboplastin Time
BACKGROUND: Timely recognition of oral anticoagulant use is critical in acute stroke but is often hampered by impaired consciousness and unavailable medication history. We investigated whether routinely available coagulation tests, prothrombin time-international normalized ratio and activated partial thromboplastin time, paired with machine learning can identify anticoagulant exposure at presentation. METHODS: We performed a multicenter diagnostic modeling study using the Japan Stroke Data Bank. Adults with ischemic or hemorrhagic stroke admitted in 2016 to 2021 comprised the derivation cohort; those in 2022 formed a temporally distinct validation cohort. Three models (random forest, extreme gradient boosting, and neural network) used prothrombin time-international normalized ratio and activated partial thromboplastin time as predictors to classify anticoagulant status: vitamin K antagonist, direct oral anticoagulant, or none. Discrimination (area under the receiver operating characteristic curve and area under the precision-recall curve), calibration, and decision curve analysis were assessed. Model outputs were implemented as bedside probability heat maps. RESULTS: Among 30 767 patients (derivation n=24 857; validation n=5910), vitamin K antagonist/direct oral anticoagulant use was 4.5%/8.2% in derivation and 2.8%/9.5% in validation. In the validation cohort, the neural network yielded the best performance: area under the receiver operating characteristic curve, 0.933 (95% CI, 0.908-0.955) and area under the precision-recall curve, 0.52 (95% CI, 0.44-0.61) for vitamin K antagonist; area under the receiver operating characteristic curve, 0.841 (95% CI, 0.822-0.858) and area under the precision-recall curve, 0.39 (95% CI, 0.35-0.43) for direct oral anticoagulant, with preserved calibration and highest net benefit across clinically relevant thresholds. Heat maps summarized class probabilities over the prothrombin time-international normalized ratio×activated partial thromboplastin time space to support rapid inference. CONCLUSIONS: A simple machine learning model using only prothrombin time-international normalized ratio and activated partial thromboplastin time classified vitamin K antagonist and direct oral anticoagulant exposure with high accuracy and practical clinical utility. This tool assists emergency decision-making when medication history is unknown, supporting the safety and timeliness of acute stroke care.
8 Apr 2026
Read appraisal →Hematology (Amsterdam, Netherlands)
Machine learning in the prediction of liver iron concentration and iron chelation therapy adjustment
OBJECTIVES: Iron chelation therapy titration is managed by hematologists who monitor iron levels and adjust medication dosages to achieve patient outcomes. This study developed a machine learning (ML) algorithm to predict the liver iron concentration (LIC) and chelation therapy adjustments. METHODS: This retrospective, single-centre cohort study included adult patients who underwent FerriScan MRI to obtain LIC for chelation therapy monitoring. Using an XgBoost-based ML framework, the proximal-time model (PTM) utilised clinical/drug, laboratory and MRI data features from one visit prior to the target visit, whereas the all-time model (ATM) utilised the data from all prior visits. RESULTS: 94 patients with 892 consecutive visits between January 2008 and November 2018 were included in this study. We assessed the prediction capabilities of the PTM and ATM in LIC, changes to chelation drug type and dosage changes. The PTM model was superior to the ATM model in all the experiments. When drug features were excluded, the CLICT model for predicting patient iron overload status improved to an AUROC of 0.83 [95% CI 0.75-0.91] for PTM; compared to an AUROC of 0.73 [95% CI 0.66-0.80] when drug features were included.For predicting changes in chelation type, the CLICT model showed AUROC of 0.83 [95% CIs 0.77-0.89] for PTM. There is high concordance of the agreement of hematologists with ML in not changing the chelation drug type. DISCUSSION/CONCLUSION: The ML model is a step toward creating a clinical decision support system tool for the prediction of LIC and iron chelation therapy adjustment in patients with haemoglobinopathies or hemolytic anemias.
5 Apr 2026
Read appraisal →Blood
Belantamab mafodotin, lenalidomide, and dexamethasone for intermediate-fit and frail patients with newly diagnosed myeloma.
The phase 1/2 BelaRd (belantamab mafodotin [belamaf], lenalidomide, and dexamethasone) study evaluated the efficacy and safety of belamaf combined with lenalidomide and dexamethasone in unfit and frail transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Part 1 (n = 36) established a recommended belamaf phase 2 dose (RP2D) of 1.9 mg/kg every 8 weeks (median follow-up, 39.3 months). In part 2, 30 patients were randomized 1:1 in group A (n = 15), where belamaf dosing was guided by ophthalmologist-assessed ocular adverse events (OAEs), whereas in group B (n = 15), belamaf dosing was based on hematologist-led vision-related anamnestic (VRA) tool and ophthalmologist-assessed grade ≥3 OAEs. Among the RP2D patients (n = 42), overall response rate was 97.6%, median progression-free survival (PFS)/overall survival have not been reached yet, and the 18-month PFS and time to progression rates were 83.0% and 97.2%, respectively. Ocular toxicities were similar between assessments by hematologists and ophthalmologists, and no ophthalmologist withholding of a hematologist-led dosing occurred. Less than 1% of patients stopped driving/reading because of OAEs. Median time to belamaf reinfusion was 13 weeks. Overall, BelaRd is an effective regimen for transplant-ineligible patients with NDMM and warrants a phase 3 study in this setting. OAEs' impact on quality of life appears limited, and implementation of the hematologist-led VRA tool may eventually reduce the necessity for ophthalmologist assessments. This trial was registered at www.clinicaltrials.gov as #NCT04808037.
5 Apr 2026
Read appraisal →The New England journal of medicine
Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation
BACKGROUND: Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. METHODS: In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. RESULTS: A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA2DS2-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding). After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidence per 100 patient-years, 16.8) in the device group and in 127 patients (incidence per 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority). Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).
4 Apr 2026
Read appraisal →Nature reviews. Clinical oncology
MicroRNAs in oncology: a translational perspective in the era of AI
Over the past three decades, knowledge of microRNA (miRNA) biology has advanced from the initial discovery of their regulatory functions to the finding of abnormal activity in leukaemias, and then to a comprehensive understanding of the roles of miRNAs in both normal physiology and most diseases, with cancer being extensively studied. miRNA dysregulation contributes to tumorigenesis, with certain miRNAs acting as either tumour suppressors or oncogenic factors in a context-dependent manner. A subset of miRNAs have shown promise as tumour biomarkers and therapeutic targets in preclinical studies, with several miRNA-based diagnostic tools and treatments progressing to clinical trials. Artificial intelligence (AI) and machine learning techniques began to be introduced into cancer research and oncology a decade ago and are now on the verge of revolutionizing biomarker identification and clinical trials. In this Review, we highlight important roles of miRNAs in cancer biology and their potential as diagnostic tools and therapeutic targets. In particular, we discuss emerging challenges and opportunities presented by AI-driven data analysis and combinatorial strategies, and how advances in these areas have addressed previous doubts on the clinical translation of miRNA-based biomarkers and therapeutics.
4 Apr 2026
Read appraisal →Journal of biophotonics
Cell-MICS: Detecting Immune Cells With Label-Free Two-Photon Autofluorescence and Deep Learning
Multiphoton imaging has been widely used for deep-tissue imaging. Although its label-free, metabolic contrast is ideal for investigating inflammation, the label-free two-photon induced autofluorescence is often regarded as less specific compared to conventional antibody markers. In this work, we investigate the potential for multiphoton imaging with computational specificity (MICS) by training a convolutional neural network on images of different immune cells. A low-complexity squeezeNet architecture was able to achieve reliable immune cell classification results (0.89 ROC-AUC, 0.95 PR-AUC for binary classification between T cells and neutrophils; 0.689 F1 score, 0.697 precision, 0.748 recall for multi-class classification between six isolated cell types). Perturbation tests confirmed that the model was not confused by the extracellular environment and that 2P-AF from NADH and FAD is equally important for the classification. In the future, deep learning could provide computational specificity for specific immune cells in unstained tissues, with great potential for label-free in vivo endomicroscopy.
4 Apr 2026
Read appraisal →N Engl J Med
Adenoviral Inciting Antigen and Somatic Hypermutation in VITT
BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare prothrombotic complication that occurs after adenoviral vector-based vaccination against coronavirus disease 2019; in rare cases, it can also occur after natural adenovirus infection. VITT is mediated by platelet-activating antibodies against the highly cationic protein platelet factor 4 (PF4). The underlying inciting antigen trigger and immunopathogenesis remain unknown. METHODS: We used antibody proteomics to determine the amino acid sequences of anti-PF4 antibodies from 21 patients with VITT and sequenced the genes encoding the immunoglobulin light-chain hypervariable region from 100 patients with VITT. To identify an adenoviral trigger, we used the antigen-binding fingerprints of anti-PF4 and anti-adenovirus protein antibodies to identify a shared serum clonotype and subsequently used adenovirus protein peptides and recombinant anti-PF4 VITT antibodies to map the mimicking linear epitope. RESULTS: Genomic and proteomic profiling of VITT antibodies revealed a shared immunoglobulin light-chain allele, IGLV3-21*02 or *03, harboring a critical somatic hypermutation, K31E. Only antibodies purified against adenoviral core protein VII (pVII) contained anti-PF4 species matching the VITT fingerprint; antibodies against intact virions or other adenoviral proteins did not. Cross-reactive IgGs were mapped to a basic linear epitope on pVII. A pathogenic anti-PF4 VITT antibody, back-mutated to germline (K31), lost its prothrombotic activity in vitro and in vivo and preferentially bound pVII, a finding that directly supported the role of the hypermutation in the antigenic shift from adenovirus pVII to PF4. CONCLUSIONS: The results of our study indicate that VITT occurs when, in persons with immunoglobulin light-chain allele IGLV3-21*02 or *03, a specific somatic hypermutation develops that affects antibodies that recognize a specific epitope on the adenoviral core protein pVII, which results in misdirection of antibody targeting toward PF4. (Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00025738; EU Post-Authorization Study Register number, EUPAS45098.).
1 Feb 2026
Read appraisal →J Clin Oncol
Genomics Define Malignant Transformation in Myeloma Precursor Conditions
Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify malignant transformation in MGUS and SMM. We introduce the concept of genomic MM and genomic MGUS to differentiate the subsets of MGUS and SMM that are biologically malignant with genomic features indistinguishable from MM from the subset that is premalignant and unlikely to progress to malignancy. Importantly, we find that most SMM has biological features of malignant transformation indistinguishable from MM. As expected, this subset that we consider having genomic MM is associated with a high risk of progression to MM although some patients remained progression-free beyond 5 years. Conversely, 60% of MGUS and 10% of SMM have no evidence of malignant transformation (genomic MGUS), with no progression during follow-up. Integration of genomic features with the 2/20/20 International Myeloma Working Group model significantly improved the prediction of progression among genomic MM. These findings support the use of genomic criteria to refine the classification and the risk stratification in myeloma precursor conditions.
1 Jan 2026
Read appraisal →Blood
Artificial intelligence in hematology
Artificial intelligence (AI) and its subdiscipline, machine learning (ML), have the potential to revolutionize health care, including hematology. The diagnosis and treatment of hematologic disorders depend on the integration of diverse data sources, such as imaging, pathology, omics, and laboratory parameters. The increasing volume and complexity of patient data have made clinical decision-making more challenging. AI/ML hold significant potential for enhancing diagnostic accuracy, risk stratification, and treatment response prediction through advanced modeling techniques. Generative AI, a recent advancement within the broader field of AI, is poised to have a profound impact on health care and hematology. Generative AI can enhance the development of novel therapeutic strategies, improve diagnostic workflows by generating high-fidelity images or pathology reports, and facilitate more personalized approaches to patient management. Its ability to augment clinical decision-making and streamline research represents a significant leap forward in the field. However, despite this potential, few AI/ML tools have been fully implemented in clinical practice due to challenges related to data quality, equity, advanced infrastructure, and the establishment of robust evaluation metrics. Despite its promise, AI implementation in hematology faces critical challenges, including bias, data quality issues, and a lack of regulatory frameworks and safety standards that keep pace with rapid technological advancements. In this review, we provide an overview of the current state of AI/ML in hematology as of 2025, identify existing gaps, and offer insights into future developments.
1 Nov 2025
Read appraisal →