Transplantation Did Not Improve OS in Patients with Lower-Risk MDS

A recent clinical trial found that transplantation in lower-risk myelodysplastic syndrome (MDS) patients with high-risk features did not improve 3-year overall survival (OS), and that quality of life (QOL) did not differ significantly between donor and nondonor patients.¹

The phase 2 multicenter trial MDS-ALLO-RISK (NCT02757989), focusing on patients with myelodysplastic syndrome (MDS), set out to investigate whether allogeneic hematopoietic stem cell transplantation (HSCT) improves OS.² A total of 77 patients with low or intermediate-1 International Prognostic Scoring System (IPSS) scores were enrolled and stratified based on the presence of a matched human leukocyte antigen (HLA) donor (62 patients in the donor arm and 15 without a donor).¹

What were the results of the trial?

OS, the primary end point of the trial, did not significantly differ between arms: 57.6% (95% CI, 46.2%-71.7%) in the donor arm vs 64.3% (95% CI, 43.5%-95.0%) in the nondonor arm (HR, 0.75; P =.53). The overall median follow-up was 35.5 months. Out of the total patients, 34 died, including 28 in the donor arm and 6 in the nondonor arm. All deceased patients in the nondonor arm died with an active disease. The lack of survival benefit with HSCT was confirmed using inverse probability of treatment weighting. Transplantation was linked to higher rates of chronic graft-vs-host disease (GVHD), severe infections, and nonrelapse mortality (24.7%). There was not a statistically significant difference in QOL among the 2 patient groups.¹

Secondary end points included complete response (CR), progression to acute myeloblastic leukemia (both evaluated at 36 months), number of patients transplanted, iron overload, evolution of ferritin levels at 12 months, QOL, and cumulative incidence of severe infections at 12 months.

CR at 36 months was higher in the donor arm (67.8%; 95% CI, 53.9%-78.3%) than in the nondonor arm (21.4%; 95% CI, 4.8-45.8; P =.002).

This trial was stopped early due to slow enrollment and futility.

“The findings highlight the need for improving posttransplant outcomes to justify HSCT in lower-risk MDS patients with poor prognostic features,” said the authors of the study.¹

Severe infections occurred in 34 patients, including 28 in the donor arm and 6 in the nondonor arm. Hemorrhages occurred in 21% of patients in the donor arm and 13% in the nondonor arm. Grade 3 cardiovascular events occurred in 7.2% of patients in the donor arm and 28.6% in the nondonor arm.

What was the study’s design?

Patients who met the inclusion criteria were included in an HLA-matched donor (related or unrelated) search, and if a donor was found, they were allocated to the donor arm. Patients without HLA-matched donors were allocated to the nondonor arm. It was recommended that donor arm patients be transplanted within 4 months. The conditioning regimen for transplantation consisted of 3.2 mg of busulfan for 2 days, 30 mg of fludarabine for 5 days, and 10 mg of anti-T-lymphocyte globulin for 3 days. Nondonor arm patients were treated according to the investigator’s choice.

What were the patient eligibility and exclusion criteria?

Patient eligibility included, but was not limited to, being aged 18 to 69 years and having MDS including, chronic myelomonocytic leukemia according to World Health Organization 2016 classification, having a low or intermediate-1 risk according to IPSS classification, having intermediate or higher IPSS-R risk, thrombocytopenia less than 20 g/L, neutropenia less than 0.5 g/L, or failure to 2 lines of therapy.¹

Patient exclusion criteria included, but were not limited to, contraindications for transplantation including renal, cardiac, respiratory or hepatic dysfunction, previous active cancer the last 3 years, or uncontrolled infection.¹

REFERENCES:

1. Sebert M, Thepot S, Cluzeau T, et al. Transplantation in lower risk MDS patients: a prospective phase 2 trial based on donor availability. Blood Adv. Published online October 8, 2025. DOI:10.1182/bloodadvances.2025017035

2. Allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome low risk. ClinicalTrials.gov. Updated August 2, 2024. Accessed October 24, 2025. https://clinicaltrials.gov/study/NCT02757989