ALL-548: Real-World Outcomes of Pediatric-Inspired AYA-15 Protocol in Adolescents and Young Adults With Acute Lymphoblastic Leukemia: A Decade of Single-Center Experience

The adoption of pediatric-inspired protocols in adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) has shown improved outcomes compared with traditional adult regimens. This study evaluated the efficacy, safety, and survival outcomes of the AYA-15 protocol in Philadelphia chromosome-negative AYA patients treated at a single tertiary center. In this retrospective cohort study, 149 patients aged ≥14 years with newly diagnosed B- or T-cell ALL were treated with the AYA-15 protocol at King Faisal Specialist Hospital and Research Centre between 2015 and 2024. Key outcomes included complete remission (CR) by day 28, measurable residual disease (MRD) status, relapse, allogeneic stem cell transplantation (allo-SCT), and survival rates. Kaplan-Meier analyses were performed for overall survival (OS), disease-free survival (DFS), and event-free survival (EFS), with subgroup comparisons by immunophenotype. The median age was 18 years (IQR, 16–23), with 54% male patients and 73% presenting with B-cell ALL. By day 28, 86% achieved morphological CR, and 76% achieved MRD-negativity, increasing to 78% postconsolidation. Over a median follow-up of 2.48 years, 17% relapsed, 19% underwent allo-SCT, and 16% died. The 5-year estimated OS, DFS, and EFS were 79% (95% CI, 72–88), 70% (95% CI, 61–80), and 59% (95% CI, 51–70), respectively. No statistically significant differences in survival were observed between B-cell and T-cell subtypes (log-rank P > 0.3). However, central nervous system (CNS) involvement at diagnosis was associated with significantly inferior overall survival ( P = 0.0006), though not with relapse risk ( P = 0.3311). Common grade ≥2 adverse events included febrile neutropenia (41% induction, 51% consolidation), elevated aspartate aminotransferase and alanine aminotransferase (64% induction, 72% consolidation), and allergic reactions (27% during consolidation). The AYA-15 pediatric-inspired protocol demonstrated favorable remission and survival outcomes in a highrisk AYA ALL cohort, with an acceptable toxicity profile. CNS disease at diagnosis remains a significant adverse prognostic factor for overall survival. These results support the routine implementation of pediatric-based regimens in older adolescents and young adults. Future analyses will explore multivariable predictors of relapse and mortality to refine risk-adapted approaches.