Impact of Epstein-Barr Virus Donor Serostatus on Post-Transplant Mortality and Post-Transplant Lymphoproliferative Disorder in Epstein-Barr Virus Seropositive Thoracic Organ Transplant Recipients: Data from the Organ Procurement and Transplantation Network.

Donor Epstein-Barr virus (EBV)-seropositive (D + ) serostatus is a risk factor for post-transplant lymphoproliferative disorder (PTLD) in EBV-seronegative recipients. The impact of donor EBV serostatus on mortality and PTLD in EBV-seropositive (R + ) thoracic organ transplant recipients is unknown. We analyzed 49 458 EBV R+ thoracic transplant recipients from the Organ Procurement and Transplantation Network (2004-2021). The primary exposure was EBV D+ serostatus; outcomes were death and PTLD. Associations were assessed using multivariable Cox and logistic regression models. EBV D+ serostatus was not associated with mortality but significantly reduced the hazard of PTLD in lung and heart-lung (L/HLT) recipients (adjusted hazard ratio, 0.59; 95% CI: 0.42-0.83). No association was observed in heart transplants. Notably, 48.7% of PTLD cases in EBV R + L/HLT occurred early after transplant when the donor was EBV-seronegative (D-). In an exploratory subgroup analysis of PTLD cases, EBV D+ serostatus was associated with lower odds of early vs late PTLD (adjusted odds ratio [aOR]: 0.40; 95% CI: 0.22-0.73). Conversely, L/HLT had twice the odds of early PTLD (aOR: 2.62; 95% CI: 1.68 - 4.08). EBV D-/R + L/HLT recipients carry a substantially higher risk of PTLD than EBV D + /R+ recipients, driven predominantly by early-onset disease.