Impacts of donor age and HLA mismatch on HCT outcomes differ according to the donor CMV serostatus in unrelated allo-HCT

• The effects of older donor age and HLA mismatch on OS significantly differed based on the donor CMV serostatus in unrelated allo-HCT.

• In unrelated allo-HCT from a CMV seronegative donor, an HLA-mismatched older donor may be able to be selected without affecting OS.

In unrelated allogeneic hematopoietic cell transplantation (allo-HCT), older and/or HLA-mismatched donors are known risk factors for survival outcomes. In healthy individuals, cytomegalovirus (CMV) seropositivity is associated with impaired adaptive immune systems. We assessed whether the adverse effects of donor risk factors are influenced by the donor CMV serostatus. We analyzed 5836 CMV seropositive patients who received unrelated allo-HCT. We divided the entire cohort into two cohorts according to the donor CMV serostatus: CMV-positive (DP) and -negative (DN). We also stratified each cohort into four groups based on donor age (≥ 40 or < 40) and HLA parity (8/8 or 7/8): Young88, Old88, Young78, and Old78. In the CMV-DP cohort, the Old88 (HR 1.20, P = 0.012), Young78 (HR 1.35, P < 0.001), and Old78 (HR 1.60, P < 0.001) groups were associated with inferior OS compared with the Young88 group. On the other hand, in the CMV-DN cohort, neither donor age nor HLA disparity was associated with inferior OS. The adverse impact of donor age was different between the cohorts (CMV-DP; HR 1.19, P = 0.001, CMV-DN; HR 1.04, P = 0.53; P for interaction 0.070), as was the impact of HLA (CMV-DP; HR 1.34, P < 0.001, CMV-DN; HR 1.08 P = 0.23; P for interaction 0.012). The impacts of donor age and HLA mismatch on OS might differ according to the donor CMV serostatus. In unrelated allo-HCT from a CMV seronegative donor, an HLA-mismatched older donor may be able to be selected without affecting OS.