Transplantation in patients with lower-risk MDS: a prospective phase 2 trial based on donor availability.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potential curative therapy for myelodysplastic syndrome (MDS), recommended in higher risk disease according to the International Prognostic Scoring System (IPSS). We conducted a phase 2 multicenter trial (MDS-ALLO-RISK) investigating whether allogeneic HSCT improves overall survival (OS) in patients with lower-risk MDS who exhibit additional high-risk features (intermediate or higher revised-IPSS risk, thrombocytopenia with <20 × 109/L, neutropenia <0.5 × 109/L, or failure to 2 lines of therapy). A total of 77 patients (median age, 62.5 years) with low or intermediate-1 IPSS scores were enrolled and stratified based on the presence of a matched HLA donor, 62 patients in the donor arm and 15 without a donor. Despite high remission rates in patients who had received a transplant (67.8% vs 21.4%), the 3-year OS did not significantly differ between arms (57.6% in the donor arm vs 64.3% in the no-donor arm; hazard ratio, 0.75; P = .53). The adjusted analysis using inverse probability of treatment weighting confirmed the lack of survival benefit with HSCT. Transplantation was associated with higher rates of chronic graft-versus-host disease, severe infections, and nonrelapse mortality (24.7%). Although quality of life improved slightly over time in patients who had received a transplant, the difference was not statistically significant. The trial was stopped early due to slow enrollment and futility. The findings highlight the need for improving posttransplant outcomes to justify HSCT in patients with lower-risk MDS with poor prognostic features. This trial was registered at www.clinicaltrials.gov as #NCT02757989.