Transplant Cell Ther. 2025 May 14. pii: S2666-6367(25)01170-4. [Epub ahead of print]
BACKGROUND: While donor age significantly impacts allogeneic hematopoietic cell transplantation (HCT) outcomes, the effect of donor cytomegalovirus (CMV) serostatus, particularly in CMV-seronegative recipients, remains a critical consideration. Donor CMV seropositivity is linked to increased CMV viremia and non-relapse mortality (NRM) in these recipients. Given the limited scope of novel antiviral prophylaxis drugs e.g., letermovir solely for CMV-seropositive recipients and the association of post-transplant cyclophosphamide (PTCy) with increased CMV reactivation, this study investigates the impact of donor CMV serostatus on outcomes in CMV-seronegative acute myeloid leukemia (AML) patients undergoing HLA-matched or mismatched unrelated donor HCT with PTCy.
METHODS: We retrospectively analyzed data from the Center for International Blood and Marrow Transplant Research, including adult CMV-seronegative AML patients who underwent unrelated donor HCT with PTCy between 2017 and 2021. Primary outcome was overall survival (OS). Secondary outcomes included relapse, NRM, and acute/chronic graft-versus-host disease (GVHD). Donor age was dichotomized at ≤32 and >32 years. Multivariable Cox proportional hazards (PH) models, stratified by donor age, and Restricted Mean Survival Time (RMST) and Restricted Mean Time Lost (RMTL) analyses were performed.
RESULTS: Of 408 CMV-seronegative recipients, 127 received transplants from CMV-seropositive donors. Baseline characteristics were well-balanced between groups. Multivariable analysis demonstrated that recipients of CMV-seropositive donors had a significantly higher hazard of mortality (HR 1.51, 95% CI 1.07-2.14, p = 0.019). Donor age and donor type did not significantly impact OS in this CMV seronegative patient population. RMST analysis showed that recipients with CMV-seronegative donors lived on average 2.95 months longer (p=0.045), while RMTL ratio was 1.34 (p=0.037), indicating that recipients of CMV-seropositive donors experienced a 34% higher risk of loss of survival time. The difference in OS was primarily driven by a trend toward increased relapse risk in the CMV-seropositive donor group (HR 1.42, 95% CI: 0.95-2.08, p = 0.06) rather than NRM (HR 1.19, 95% CI: 0.66-2.13, p = 0.56).
CONCLUSIONS: In CMV-seronegative adult AML patients undergoing unrelated donor HCT with PTCy, CMV-seropositive donors are associated with worse OS than CMV-seronegative donors, likely linked to higher relapse risk. These findings underscore the importance of considering donor CMV serostatus in donor selection for CMV-seronegative recipients undergoing HCT with PTCy. Further investigation is necessary to optimize donor selection strategies and improve outcomes in this patient population.
Keywords: CMV; CMV-negative recipient; Cytomegalovirus; Donor age; HLA matched unrelated donor; Haploidentical; MMUD; MUD; Mismatched unrelated donor; PTCy; post-transplantation cyclophosphamide CMV-positive donor