Non-T-Depleted Haploidentical Transplantation Compared to Allogeneic Transplantation From Matched Siblings or Unrelated Donors in Patients With Secondary AML in First Complete Remission: A Study From the ALWP/EBMT

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for secondary acute myeloid leukemia (sAML). This study compared haploidentical donor (Haplo), matched sibling donor (MSD), and matched unrelated donor (MUD) HSCT in patients with sAML in first complete remission (CR1). Data from 3862 patients (Haplo = 643, MSD = 715, MUD = 2504) transplanted between 2010 and 2022 were analyzed, with a median follow-up of 3.3 years. Groups differed in patient and donor age, conditioning regimen, stem cell source, and graft-versus-host disease (GVHD) prophylaxis. Multivariate analysis showed that MSD-HSCT had a higher relapse risk than Haplo-HSCT (hazard ratio [HR]: 1.64) but lower non-relapse mortality (NRM, HR: 0.32) and acute GVHD risk (HR: 0.54 for grade II–IV), leading to an overall survival (OS) benefit (HR: 0.76). MUD-HSCT had lower NRM than Haplo-HSCT (HR: 0.63) but there were no significant differences in OS or GVHD risk. Donor type did not impact leukemia-free survival (LFS) or GVHD-free and relapse-free survival (GRFS). Adverse cytogenetics and reduced-intensity conditioning were associated with increased relapse risk, while lower Karnofsky scores, older age, and adverse cytogenetics independently predicted worse NRM, LFS, OS, and GRFS outcomes. Female-to-male donor-recipient pairs had an increased risk of chronic GVHD. In this registry-based analysis, MSD offered the best outcomes for sAML in CR1. Haplo-HSCT was comparable to MUD-HSCT, despite a higher NRM, and achieved long-term disease control in 60% of patients due to a low relapse incidence. In the absence of an MSD, both Haplo and MUD are viable alternatives.