Germline DDX41 defines a distinct subgroup in MDS undergoing transplantation with reduced relapse and improved survival.

Germline DDX41 variants in MDS are linked to a 57% reduction in 2-year relapse incidence after transplantation compared to wild-type patients.

• Why it matters: Understanding the impact of DDX41 status on transplant outcomes can improve risk stratification and treatment planning for MDS patients, addressing a current knowledge gap.
• What they did: The study analyzed 1,514 MDS patients undergoing transplantation, identifying 49 with pathogenic/likely pathogenic germline DDX41 variants and comparing their outcomes to a wild-type group, focusing on relapse, survival, and toxicity.
• The result: Patients with DDX41 variants showed significantly lower relapse risk (hazard ratio 0.43) and improved disease-free survival (hazard ratio 0.62), especially under reduced-intensity conditioning, with no increase in non-relapse mortality or graft-versus-host disease.