Risk and prognosis of post-transplant lymphoproliferative disease in Epstein-Barr virus-seronegative kidney transplant recipients - An observational cohort study from Norway and western Denmark.

Post-transplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007-2021, and estimated the cumulative incidence, risk and prognosis of PTLD. In total, 80 of 5,084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% confidence interval (CI) 13.9-67.9) in EBV-seronegative vs. EBV-seropositive adults and 5.4 (95% CI 1.1-26.9) in children. Recipients receiving induction therapy with anti-thymocyte globulin had an increased risk of PTLD, HR=4.4 (95% CI 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD, HR=0.20 (95% 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs. without PTLD (HR=3.3 (95% CI 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.