Myeloablative dose of busulfan and fludarabine combined with in vivo T-cell depletion is a safe and effective conditioning for acute myeloid leukaemia and myelodysplastic syndrome patients

Background: Allogeneic haematopoietic stem cell transplant (HSCT) is a curative strategy for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). The prediction of transplant related mortality (TRM) using the HCT-CI score and an arbitrary upper limit of 55 years for administering myeloablative conditioning (MAC) are common strategies to ensure a safe procedure. Reduced toxicity conditioning regimens are additional methods to deliver safe and effective myeloablation. Objectives: Herein we report the outcome of AML and MDS patients conditioned with fludarabine and a myeloablative dose of busulfan (FB4) stratified by age and HCT-CI score. The primary objective was overall survival (OS) for patients aged ≥55 years. Secondary objectives were total OS, TRM, graft versus-host disease (GVHD) and GVHD-relapse-free survival (GRFS). Results: The two years' OS in patients aged < 55 and aged ≥ 55 were 72% and 51%, respectively. In patients aged ≥55 with an HCT-CI <2, the estimated two years' OS was 64%, with median OS not reached. In those with HCT-CI ≥2, the two-year OS was 43%, with median OS of 14 months. The total cumulative incidence of relapse was 30% regardless of age or HCT-CI score. Conclusions: FB4 conditioning regimen offers a high rate of prolonged remission with a relapse rate similar to that reported in previous studies. These positive outcomes suggest that this conditioning platform can be offered to patients aged ≥55 in absence of comorbidities, and that age should not be the sole determinate of conditioning intensity.