Non-myeloablative versus reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients aged ≥65: a study from the ALWP of EBMT

The optimal conditioning intensity for allogeneic hematopoietic stem cell transplantation (allo-HCT) in elderly acute myeloid leukemia (AML) remains elusive. We retrospectively analyzed 2900 AML patients aged ≥65 in complete remission who underwent allo-HCT from 2004 to 2021. Conditioning was classified as reduced-intensity conditioning (RIC: fludarabine with busulfan, melphalan, or treosulfan) or non-myeloablative (NMA: fludarabine with total body irradiation). Primary endpoints were overall survival (OS) and leukemia-free survival (LFS); secondary endpoints included non-relapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), and GVHD/relapse-free survival (GRFS). With follow-up censored to account for differences between arms, OS, LFS, and NRM at 2 years were similar between RIC and NMA on multivariable analysis. Peripheral blood stem cells (PBSC) were independently associated with superior OS (HR 0.67, p = 0.002) and LFS (HR 0.71, p = 0.008) versus bone marrow grafts. GRFS was equivalent between conditioning intensities, although RIC was associated with higher acute GVHD and NMA with higher extensive chronic GVHD. In exploratory analysis, OS and LFS were similar across RIC regimens (Flu/Bu2 as reference: Flu/Mel OS HR 0.91, p = 0.53; Flu/Treo OS HR 0.89, p = 0.42). In older AML patients in remission, RIC and NMA yield comparable survival and NRM; PBSC grafts may be associated with superior outcomes although this warrants validation.