Donor-Recipient Epstein-Barr Virus Serostatus and Time-Varying Risk of Posttransplant Lymphoproliferative Disorder in...

Prior studies and guidelines emphasize PTLD-risk for Epstein-Barr virus (EBV) mismatched (D+/R-) recipients. However, risk among D-/R- kidney recipients remains poorly defined. We evaluated PTLD-risk by donor-recipient EBV serostatus, including D-/R-, and time-varying impact of PTLD on mortality in kidney transplant recipients.

This retrospective cohort included deceased donor kidney transplants from the US Scientific Registry of Transplant Recipients (2003-2023). Recipient and donor-recipient EBV serostatus were categorical exposures. Time-to-PTLD was analyzed using Kaplan-Meier methods and adjusted Cox models, stratified into 0-1, 1-2, and 2-3 years to address non-proportional hazards. Secondary outcomes included mortality and all-cause graft failure (ACGF), with PTLD modeled as a time-dependent exposure. Effect modification across key subgroups was evaluated.

Among 309 585 recipients (2.35 million person-years), 3147 PTLD events (1.1%) occurred, largely within the first year. Incidence was highest for D+/R- (3%) and D-/R- (1.8%) (p < 0.001). First-year PTLD-risk was highest for D+/R- (HR 17.8 [95% CI: 10.4, 30.5]) and D-/R- (HR 8.2 [95% CI: 4.2, 15.8]) recipients. PTLD was associated with increased mortality (HR 4.5 [95% CI: 4.3, 4.8]) and ACGF (HR 3.7 [95% CI: 3.5, 3.9]), with relatively higher mortality-risk for pediatric recipients (ratio of HRs 1.5). Among 82 detailed PTLD cases, most were B-cell (89%), monoclonal (63%), and EBV-positive (78%), with mixed WHO class and site-involvement.

EBV D+/R- recipients experienced highest and sustained 3-year PTLD-risk, while D-/R- recipients faced previously under-recognized early risk. PTLD was strongly linked to mortality and ACGF, refining counselling and supporting targeted surveillance for high-risk groups.