Pediatric-inspired regimens and HSCT for adolescents and young adults with acute lymphoblastic leukemia

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported but confidence intervals exclude null

• Effect Size: Pediatric regimens: RR 1.40 (1.18-1.65); HSCT: RR 0.72 (0.61-0.84)

• Primary Outcome: 5-year overall survival

• Nnt Or Sensitivity: Treatment-related mortality reduction with pediatric regimens: RR 0.29 (0.09-0.90)

• Confidence Interval: 95% confidence intervals provided for all estimates

Clinical Application

Pediatric regimens may be feasible in AYA populations but require careful toxicity monitoring; HSCT decisions require individualized risk-benefit assessment Relevant to Australian haematology practice; aligns with current ALLG (Australasian Leukaemia and Lymphoma Group) protocols; PBS coverage considerations for asparaginase-based regimens Adolescents and young adults aged 15-39 years with Philadelphia chromosome-negative ALL in first complete remission

Abstract

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.

References

1. 1.Sereda, Y., Mai, H. J., Kanaan, G., Melson, J. W., Terasawa, T., Cheung, M. C., Stock, W., Wolfson, J. A., Saldanha, I. J., & Balk, E. M. (2026). Pediatric-inspired regimens and HSCT for adolescents and young adults with acute lymphoblastic leukemia. Blood Advances. https://doi.org/10.1182/bloodadvances.2025018736