Abstract

A common and potentially fatal post-solid organ transplant (SOT) complication is post-transplant lymphoproliferative disorder (PTLD). While the association of Epstein-Barr virus (EBV) with the development of PTLD is well recognized, little is known about the etiology of EBV-negative PTLD. To characterize the differences between EBV-positive and EBV-negative PTLD to better understand the pathogenesis of EBV-negative PTLD. This was a retrospective study that reviewed patients who developed PTLD after SOT. Data was collected on PTLD patients (>18 years) from 2011 to 2021. Data included demographics, SOT type, time from SOT to PTLD development, tumor EBV status, PTLD site, histopathological morphology, tumor markers, and overall survival. EBV tumor status was compared using χ2, Fisher's Exact, and Wilcoxon Rank Sum tests. A single, large academic center. A total of 99 patients met the inclusion criteria. Of those, 45.5% were EBV-positive and 54.5% were EBV-negative. Tumor EBV status did not differ by race, but males were more likely to be EBV-negative (63% v. 44.4% of females, p=0.065). EBV tumor status did not differ by SOT type. The interval between SOT and PTLD diagnosis was longer in EBV-negative patients (8.68 years) than EBV-positive patients (4.93 years) (p=0.001). There was a significant difference in EBV-negative PTLD site (p=0.046) and PTLD subtypes (p=0.002). Site of EBV-negative PTLD consisted of gastrointestinal (38.9%), head/neck (11.1%), liver/spleen (11.1%), CNS (3.7%), other lymph (24%), and other non-lymph (11.1%). Monomorphic (65.5%) and T-cell (90%) subtypes were more common in EBV-negative patients, compared to the polymorphic (15.4%) and plasmablastic/plasmacytic (27.3%) subtypes. Expression of CD20 did not differ by tumor EBV status. Those who were CD30-negative were more likely to be EBV-negative (90% v. 25%, p=<0.001). Those who were CD138-negative were more likely to be EBV-negative (75% v. 26.7%, p=0.012). There was no difference in overall survival by tumor EBV status. This single institution retrospective review shows that there are distinct differences between EBV-negative and EBV-positive PTLD. EBV-negative PTLD has a longer interval from SOT to PTLD development, is more likely to occur in the gastrointestinal tract, and is more likely to have a monomorphic morphology.

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