Germline DDX41 variants linked to lower relapse after transplantation in MDS

An observational study in Blood examined whether germline DDX41 status was associated with outcomes after allogeneic transplantation for myelodysplastic neoplasms (MDS). Researchers analyzed 1,514 patients transplanted before routine DDX41 testing, comparing carriers of pathogenic or likely pathogenic variants with a wild-type comparator. Outcomes included relapse, disease-free survival, non-relapse mortality and graft-versus-host disease.

Forty-nine patients (3.2%) carried pathogenic or likely pathogenic germline DDX41 variants; 19 of these (39%) also had a somatic DDX41 mutation. Carriers were older than comparators (median 63 versus 59 years), had lower IPSS-M risk and lacked TP53 mutations (0% versus 21%). Two-year relapse incidence was 17% versus 34% (p=0.01). In adjusted analyses, germline DDX41 variants were associated with lower relapse risk (hazard ratio 0.43, 95% CI 0.21–0.88), with this association concentrated in the reduced-intensity/nonmyeloablative conditioning stratum.

Adjusted disease-free survival was also better among carriers (hazard ratio 0.62, 95% CI 0.41–0.95), with no significant association with non-relapse mortality or graft-versus-host disease. The findings support considering germline DDX41 status in transplant planning, but do not establish an optimal conditioning regimen. Interpretation is limited by the observational design, the small variant-positive subgroup and availability of only the abstract for this update.