A Scheduled Program of Molecular Screening for Epstein-Barr Virus Decreases the Incidence of Post-transplantation Lymphoproliferative Disease in Pediatric Liver Transplantation

Abstract

This is a cohort, retrospective, comparative study of all liver transplant recipients from a single center, from May 1998 to July 2015. Patients were divided into two groups according to the type of Epstein-Barr viral load monitoring. For group I (1998–2007), polymerase chain reaction (PCR) was not available or it was only qualitative with limited access. For group II (2008–2015), we used periodically scheduled quantitative PCR in plasma and leukocytes, with aggressive tapering of immunosuppression as soon as viral replication was detected. Ninety-eight recipients were included, 41 (41.8%) were Epstein-Barr virus (EBV) − seronegative before liver transplantation (LT). EBV replication was confirmed in 74 patients (75.5%), being more frequent in seronegative (87.8%) than seropositive patients (66.6%). Eight recipients (8.1%) developed post-transplantation lymphoproliferative disorder (PTLD) on average at 14.3 months post-LT, seven of eight were <3 years at LT, four of eight were D+/R− for EBV, and all had post-LT EBV replication confirmed by PCR. PTLD was classified as lymphoma (n = 4), polymorphic polyclonal (n = 3), and lymphoid hyperplasia (n = 1). Five patients died, and three cleared PTLD after immunosuppression tapering or interruption. There were no significant differences in the etiology, age at LT (5.6 vs. 7.3 years, P = .069), patients <4 years (53.2% vs. 35.3%, P = .103), or EBV seronegative recipients (44.7% vs. 37.3%, P = .54); however, the incidence of PTLD decreased from 14.9% to 1.9% (P = .026), and graft rejection from 51.1% to 29.4% (P = .039). One- and 5-year patient survival rates were 94.7% and 85%, respectively, with no differences between groups. This strategy dramatically decreased the incidence of PTLD (14.9% vs. 1.9%), without increasing the incidence of rejection; therefore, we recommend that it should be used in the follow-up of all pediatric LT recipients.