Adolescents and young adults (AYA) with acute myeloid leukemia (AML) represent a biologically and clinically distinct population managed across pediatric and adult oncology services, with no established optimal treatment paradigm. In this single-center retrospective study, we analyzed 81 AYA patients aged 14 to 29 years with newly diagnosed AML treated at Memorial Sloan Kettering Cancer Center between 2010 and 2025. Patients were stratified by treating service, European LeukemiaNet (ELN) 2022 risk category, and induction regimen. Pediatric patients received 2 cycles of cytarabine, daunorubicin, and etoposide-based induction, whereas adult patients received 1 cycle of cytarabine plus daunorubicin (7+3) induction, 3 of whom required 7+3 reinduction, followed by risk-adapted consolidation including allogeneic hematopoietic stem cell transplantation. Composite complete response rates were similar between adult and pediatric cohorts (79% vs 78%), as were rates of minimal residual disease negativity by multicolor flow cytometry among responders (63% vs 55%). Despite comparable depth of response, 5-year overall survival favored adult-service patients in both the full cohort (77.9% vs 56.7%) and the ELN 2022 intermediate-adverse risk subgroup (62.7% vs 47.9%), whereas relapse-free survival was nearly identical. On multivariable analysis, ELN 2022 risk retained independent prognostic significance, whereas treatment protocol did not. These findings demonstrate that pediatric-style and adult AML regimens achieve comparable remission depth in AYA patients. The survival advantage observed with adult protocols challenges the assumption that further cytotoxic intensification improves outcomes in this population.
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