Pediatric-Inspired Regimens & HSCT for Adolescents & Young Adults with Acute Lymphoblastic Leukemia: Systematic Reviews

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") versus non-asparaginase-based ("adult") regimens, and (2) allogeneic hematopoietic stem cell transplantation (HSCT) versus no HSCT for AYAs (15-39 years old) with ALL in first complete remission (CR). Data Sources: PubMed, CINAHL, and PsycINFO from inception through November 29, 2023. Eligible studies compared regimens or use of HSCT and reported survival, remission, toxicity, or quality of life in AYAs. We included 19 studies (14 comparative, 5 single-group; N=3,607) comparing regimens and 7 studies (N=7,492) 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, 1.18-1.65), event-free survival (RR 1.80, 1.13-2.85), disease-free survival (DFS) (RR 1.55, 1.32-1.82), and lower treatment-related mortality (TRM) (RR 0.29, 0.09-0.90).. HSCT was associated with lower 5-year OS (RR 0.72, 0.61-0.84) and DFS (RR 0.78, 0.68-0.90), and higher non-relapse mortality (RR 2.70, 1.18 - 6.18) and TRM (HR 6.88, 3.02-15.70). Relapse risk varied by time point. In AYA with Ph-negative ALL, pediatric regimens may improve survival; toxicity-related evidence remains limited. HSCT may lead to inferior overall survival and DFS. With a dearth of RCTs, low-certainty evidence highlights the need for high quality studies and sub-analyses of AYAs.