Role of Donor Cytomegalovirus Serostatus in Cytomegalovirus-Seronegative Recipients of Unrelated Donor Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Prophylaxis

Rohtesh S Mehta; Yosra M Aljawai; Taha Al-Juhaishi; Jennifer Saultz; Filippo Milano; Jennifer A Kanakry; Christopher G Kanakry; Aleksandr Lazaryan

doi:10.1016/j.jtct.2025.05.005

Role of Donor Cytomegalovirus Serostatus in Cytomegalovirus-Seronegative Recipients of Unrelated Donor Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Prophylaxis

Transplant Cell Ther. 2025 May 14:S2666-6367(25)01170-4. doi: 10.1016/j.jtct.2025.05.005. Online ahead of print.

Authors

Rohtesh S Mehta¹, Yosra M Aljawai², Taha Al-Juhaishi³, Jennifer Saultz⁴, Filippo Milano⁵, Jennifer A Kanakry⁶, Christopher G Kanakry⁶, Aleksandr Lazaryan⁷

Affiliations

¹ Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: rmehta1@mdanderson.org.
² Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
³ OU Health Stephenson Cancer Center, Oklahoma City, Oklahoma.
⁴ Division of Hematology/Oncology, Oregon Health and Science University, Portland, Oregon.
⁵ Fred Hutchinson Cancer Center, Seattle, Washington.
⁶ Center for Immuno-Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
⁷ Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida.

PMID: 40379049
DOI: 10.1016/j.jtct.2025.05.005

Abstract

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, eg, 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. 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. Donor age was dichotomized at ≤32 and >32 years. Multivariable Cox proportional hazards models, stratified by donor age, and Restricted Mean Survival Time (RMST) and Restricted Mean Time Lost (RMTL) analyses were performed. 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 (hazard ratios [HR] 1.51, 95% confidence interval [CI] 1.07 to 2.14, P = .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 = .045), while RMTL ratio was 1.34 (P = .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 to 2.08, P = .06) rather than NRM (HR 1.19, 95% CI: 0.66 to 2.13, P = .56). 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.