Transplantation in lower risk MDS patients: a prospective phase 2 trial based on donor availability Open Access

• Three-year overall survival is not improved by transplantation in lower risk MDS patients with high-risk features

• Quality of life does not differ in donor and no-donor group

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potential curative therapy for myelodysplastic syndrome (MDS), recommended in higher-risk according to IPSS. We conducted a phase II multicenter trial (MDS-ALLO-RISK, CNT: NCT02757989) investigating whether allogeneic hematopoietic stem cell transplantation (HSCT) improves overall survival (OS) in patients with lower-risk myelodysplastic syndromes (MDS) who exhibit additional high-risk features (intermediate or higher IPSS-R risk, thrombocytopenia < 20 G/L, neutropenia < 0.5 G/L or failure to 2 lines of therapy). A total of 77 patients (median age 62.5) 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 transplanted patients (67.8% vs. 21.4%), the 3-year OS did not significantly differ between arms (57.6% in donor arm vs. 64.3% in non-donor arm, HR 0.75, p=0.53). The adjusted analysis using inverse probability of treatment weighting (IPTW) confirmed the lack of survival benefit with HSCT. Transplantation was associated with higher rates of chronic graft-versus-host disease (GVHD), severe infections, and non-relapse mortality (24.7%). Although quality of life improved slightly over time in transplanted patients, the difference was not statistically significant. The trial was stopped early due to slow enrollment and futility. The findings highlight the need for improving post-transplant outcomes to justify HSCT in lower-risk MDS patients with poor prognostic features.