Survival benefits from reduced-intensity conditioning in allogeneic stem cell transplantation for young lower-risk MDS patients without significant comorbidities

Objective: The aim of this study was to determine the optimum conditioning intensity for allogeneic stem cell transplantation (SCT) in young (age ≤50), lower-risk (INT-1 by IPSS) Myelodysplastic syndrome (MDS) patients without significant comorbidities (hematopoietic cell transplantation-comorbidity index score ≤3). Methods: Transplant outcomes from 46 consecutive patients were retrospectively analyzed according to the conditioning intensity: reduced-intensity conditioning (RIC; n=14), intensified RIC by adding low-dose total body irradiation (iRIC; n=15), and myeloablative conditioning (MAC; n=17). Results: After a median follow-up of 73.7months, RIC had a better 4-yr overall survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate analysis showed that RIC was associated with improved OS compared with the MAC [relative risk (RR) of 0.08, P=0.022] because of a lower transplant-related mortality (TRM) (RR, 0.08, P=0.035). iRIC failed to show survival benefits over the MAC (RR of 0.77, P=0.689) because of similarly high TRM (RR of 0.41, P=0.480). Cumulative incidence of acute and chronic graft-versus-host disease (GVHD) after RIC was higher, but GVHD-specific survival was significantly better (RIC 100% vs. iRIC 45.7% vs. MAC, P=0.018). Relapse rate was not different among the three groups, but in the RIC group, azacitidine was available and useful for inducing remission in two patients. Conclusion: This study shows that RIC improved OS by directly lowering TRM and indirectly giving an additional chance for relapsed MDS in the era of hypomethylating treatment. RIC-SCT should be considered for relative healthy lower-risk MDS patients.