Busulfan-Fludarabine Versus Busulfan-Cyclophosphamide for Allogeneic Transplant in Acute Myeloid Leukemia: Long Term Analysis of GITMO AML-R2 Trial

Abstract

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n= 125) and the combination of busulfan and fludarabine (BuFlu, n= 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs 20%, p= 0.0388). This difference was higher in patients older than 51 years (11 % in BuFlu vs 27% in BuCy2, p= 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse free-survival (GRFS) in BuFlu arm vs the BuCy2 arm was 25% vs 20% at 4 years and 20% vs 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.