Circulating Epstein–Barr virus DNA and high‐risk extra‐nodal involvement identify disease‐specific mortality in post‐transplant lymphoproliferative disorder

Summary Post‐transplant lymphoproliferative disorder (PTLD) is a heterogeneous disorder arising in the context of immunosuppression after solid organ transplantation. Determinants of PTLD‐specific mortality remain poorly defined, as conventional survival analyses may not adequately capture disease‐attributable risk given substantial competing mortality. We performed a retrospective analysis of 75 solid organ transplant recipients with PTLD, using a competing‐risk framework with Fine–Gray subdistribution hazard regression to identify factors associated with PTLD‐related death, accounting for non‐PTLD mortality. Over a median follow‐up of 71.0 months, 35 patients (46.7%) died, of whom 25 (71.4%) experienced PTLD‐related death. After adjustment for International Prognostic Index (IPI), high‐risk extra‐nodal involvement (bone marrow or central nervous system) remained associated with PTLD‐related mortality (subdistribution hazard ratio [sHR], 3.82; 95% confidence interval [CI], 1.67–8.73; p = 0.001), as did detectable circulating Epstein–Barr virus (EBV) deoxyribonucleic acid (DNA) (sHR, 4.38; 95% CI, 1.63–11.76; p = 0.003). Combined tissue and blood EBV stratification further revealed a hierarchical mortality gradient across four EBV‐defined subgroups (dual‐positive to dual‐negative). High‐risk extra‐nodal involvement and detectable circulating EBV DNA are independently associated with PTLD‐attributable mortality after adjustment for IPI. Combined tissue and circulating EBV assessment may provide complementary prognostic information. Prospective validation in larger multicentre cohorts is warranted.