9 Kinetics of Primary Epstein-Barr Virus Infection After Pediatric Heart Transplantation

Abstract

Background: Primary Epstein-Barr virus (EBV) infection frequently occurs early after transplantation (Tx) in seronegative pediatric heart Tx recipients who receive organs from seropositive donors and is the key risk factor for the development of post-transplant lymphoproliferative disorder (PTLD). The routine use of post-Tx EBV-PCR monitoring offers the opportunity to study the time course of primary EBV infection and the influence of differing immunosuppressive regimens.Methods: We studied 15 consecutive seronegative recipients who received a primary heart Tx from a seropositive donor. All were managed with tacrolimus-based immunosuppression with 9/15 also receiving 5 days of induction with rabbit antithymocyte globulin (Thymoglobulin). Surveillance was by whole blood real-time EBV-PCR approximately monthly for the first 6 months, then every 2 months for 6 months, then approximately quarterly thereafter.Results: Mean age at transplant was 5.4 years, and mean donor age was 8 years. Positive donor EBV serostatus prior to any donor transfusion was confirmed in 6 cases. One patient developed PTLD. A total of 270 PCR measurements were made (average 18/pt). 12/15 experienced primary EBV infection with first positive PCR 24-307 days post-Tx; median 38 days (Thymoglobulin pts 33d vs. non-Thymoglobulin pts 93d). Of 12 patients who developed detectable viral loads, 7 (58%) did so within 6 weeks of Tx. Peak EBV viral load ranged from 2,600 to 380,000 copies/ml; median 28,500 copies/ml (Thymoglobulin pts 26,000 vs. non-Thymoglobulin pts 47,000). Time to peak viral load was 32-1023 days, median 177 (Thymoglobulin pts 121d vs. non-Thymoglobulin pts 239d). Of the 3 patients who never developed a measurable viral load, none had pre-transfusion confirmation of donor seropositive status. Seronegative recipients with seronegative donors have not demonstrated early (first six weeks) viral loads, and screening of filtered blood products are also EBV-PCR negative suggesting that the loads observed in this study were not due to blood product use during cardiopulmonary bypass.Conclusions: EBV seronegative pediatric Tx recipients receiving hearts from seropositive donors experience very early EBV infection with evidence of viremia often within 4-6 weeks of Tx. Induction therapy may be associated with earlier viremia. EBV-PCR screening more frequently than monthly maybe indicated early after Tx in this population if any form of experimental / therapeutic intervention is planned at the time of primary EBV infection.