Impact of Pre-Transplant Hypomethylating Agents on Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation in Myelodysplastic Syndrome With Good or Intermediate-Risk Cytogenetics.

Allogeneic stem cell transplant (Allo-SCT) remains the only curative option for patients with myelodysplastic syndrome (MDS). The benefit of cytoreduction with hypomethylating agents (HMAs) prior to reduced-intensity conditioning (RIC) transplant, particularly in patients with less than 10% bone marrow blasts, remains uncertain. To evaluate the impact of pretransplant HMA in a large registry-based cohort of patients with MDS who underwent RIC Allo-SCT. This retrospective study utilized registry data to analyze transplant outcomes among patients with MDS who received pretransplant HMA and those who proceeded directly to RIC Allo-SCT without HMA. The primary endpoints were relapse-free survival (RFS), overall survival (OS), transplant-related mortality (TRM), and graft-versus-host disease (GVHD). Groups were balanced for key baseline variables, including age, donor type, disease risk, blast percentage, performance status, and conditioning regimen. Pretransplant HMA use was associated with significantly worse RFS and OS compared to the non-HMA-treated group, with no significant differences in TRM or the incidence of acute or chronic GVHD. These findings remained consistent after adjustment for confounding factors and exclusion of patients with elevated blasts at diagnosis. Pretransplant HMA may negatively impact transplant outcomes in lower-blast MDS, underscoring the need for prospective studies to better define its role in transplant sequencing.