Impact of the combination of donor age and HLA disparity on the outcomes of unrelated bone marrow transplantation

Impact of donor age considering HLA disparity on hematopoietic cell transplantation (HCT) outcomes has not been fully evaluated. We evaluated 8486 patients who received unrelated bone marrow transplantation (UR-BMT) from 8/8 or 7/8 HLA-matched donors. Compared to 8/8 HLA-matched younger donors (<40 years), 8/8 HLA-matched older donors (subdistribution hazard ratio [SHR], 1.16; 95% CI, 0.97–1.38) and 7/8 HLA-matched younger donors (SHR, 1.33; 95% CI, 1.11–1.58) were associated with increased risk of grade III–IV acute graft-versus-host disease (aGVHD). 7/8 HLA-matched older donors had further increased risk (SHR, 2.00; 95% CI, 1.68–2.38) due to interaction between donor age and HLA disparity (p for interaction = 0.038). Progression-free survival (PFS) after UR-BMT with 8/8 HLA-matched younger donors was comparable to that after UR-BMT with 8/8 HLA-matched older donors, whereas UR-BMT with 7/8 HLA-matched younger or older donors was significantly associated with lower PFS than UR-BMT with 8/8 HLA-matched younger donors (younger donor; HR, 1.12; 95% CI, 1.04–1.21, older donor; HR, 1.28; 95% CI, 1.17–1.40; p for interaction = 0.079). In conclusion, adverse effect of increased donor age requires attention, especially in HLA-mismatched UR-BMT due to interaction between donor age and HLA disparity. Intensive aGVHD prophylaxis may be required to improve outcomes after HCT with mismatched older donors.