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