Allogeneic Hematopoietic Stem Cell Transplantation in Adolescents and Young Adults With Acute Lymphoblastic Leukemia—A Retrospective, Dual-Center Study

Survival outcomes for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have improved with modern frontline therapies and minimal residual disease (MRD)-guided strategies. As a result, allogeneic hematopoietic cell transplantation (HCT) is increasingly deferred in first remission (CR1) and used in the relapsed setting. However, data on HCT outcomes in second remission (CR2) remain limited in AYAs. We conducted a dual-center retrospective study of AYA patients aged 15–40 years who underwent HCT in CR2 between 2010 and 2022. Among 164 patients, the median age was 25 years; 66% were male and 80% had B-ALL. Frontline therapies included pediatric-inspired (54%) and hyperCVAD-based (33%) regimens. Most received myeloablative conditioning (74%), and 67% were MRD-negative at HCT. At a median follow-up of 36 months, 3-year overall survival (OS) and progression-free survival (PFS) were 53% and 46%. The 3-year cumulative incidences of relapse and non-relapse mortality were 36% and 18%, respectively. The 6-month incidence of grade 2–4 acute graft-versus-host disease (GVHD) was 36%, and grade 3–4 was 14%. Chronic GVHD occurred in 27% at 3 years, with 37% moderate and 25% severe. On multivariable analysis, a HCT-specific comorbidity index > 3 was independently associated with inferior OS, PFS, and higher non-relapse mortality. MRD positivity predicted worse PFS and higher relapse risk but not OS. These findings support HCT in CR2 as a curative option for AYA patients with ALL. Outcomes are influenced by MRD status and comorbidities, underscoring the need for risk-adapted transplant strategies.