Association of Antiviral Prophylaxis and Rituximab Use with Post-transplant Lymphoproliferative Disorders (PTLD): A Nationwide Cohort Study

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein-Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation and outcome of histologically-proven PTLD. We included 4'765 patients with a follow-up duration of 23`807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV-positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years post-transplant were 3.51; 2.24; 1.75/1'000 py and 0.44; 0.25; 0.29/1'000 py for EBV- PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199-1.436], p=0.264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751-6.521], p=0.150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but (57/4'574) patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077-0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD