Elisa Colombini1, Isabella Guzzo1, Federica Morolli1, Germana Longo2, Cristina Russo3, Alessandra Lombardi4, Pietro Merli4, Luisa Barzon5, Luisa Murer2, Simone Piga6, Marta Luisa Ciofi Degli Atti6, Franco Locatelli4,7, Luca Dello Strologo8. 1. Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy. 2. Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Pediatrics, University of Padova, Padova, Italy. 3. Virology Unit, Bambino Gesù Children's Research Hospital-IRCCS, Rome, Italy. 4. Hematology and Oncology, Bambino Gesù Children's Research Hospital-RCCS, Rome, Italy. 5. Department of Molecular Medicine, University of Padua, Padua, Italy. 6. Unit of Clinical Epidemiology, Bambino Gesù Children's Research Hospital-IRCCS, Rome, Italy. 7. University of Pavia, Pavia, Italy. 8. Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy. luca.dellostrologo@opbg.net.
Abstract
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation that can be classified into two major subtypes, namely, early lesions and non-early lesions, based on histopathological findings. In the vast majority of cases, proliferating cells are B lymphocytes and, most frequently, proliferation is induced by Epstein-Barr virus (EBV) infection. METHODS: The aim of our study was to evaluate the natural history of EBV infection and its possible evolution toward PTLD in a pediatric cohort of patients who received a renal transplant between January 2000 and December 2013. A total of 304 patients were evaluated for this study, of whom 103 tested seronegative for EBV at transplantation. RESULTS: Following transplantation, 50 of the 103 seronegative patients (48.5%) developed a first EBV infection, based on the results of PCR assays for EBV DNA, with 19 of these patients ultimately reverting to the negative state (<3000 copies/ml). Among the 201 seropositive patients only 40 (19.9%) presented a reactivation of EBV. Non-early lesions PTLD was diagnosed in ten patients, and early lesions PTLD was diagnosed in five patients. In all cases a positive EBV viral load had been detected at some stage of the follow-up. Having a maximum peak of EBV viral load above the median value observed in the whole cohort (59,909.5 copies/ml) was a significant and independent predictor of non-early lesions PTLD and all PTLD onset. CONCLUSIONS: A high PCR EBV viral load is correlated with the probability of developing PTLD. The definition of a reliable marker is essential to identify patients more at risk of PTLD and to personalize the clinical approach to the single patient.
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation that can be classified into two major subtypes, namely, early lesions and non-early lesions, based on histopathological findings. In the vast majority of cases, proliferating cells are B lymphocytes and, most frequently, proliferation is induced by Epstein-Barr virus (EBV) infection. METHODS: The aim of our study was to evaluate the natural history of EBV infection and its possible evolution toward PTLD in a pediatric cohort of patients who received a renal transplant between January 2000 and December 2013. A total of 304 patients were evaluated for this study, of whom 103 tested seronegative for EBV at transplantation. RESULTS: Following transplantation, 50 of the 103 seronegative patients (48.5%) developed a first EBV infection, based on the results of PCR assays for EBV DNA, with 19 of these patients ultimately reverting to the negative state (<3000 copies/ml). Among the 201 seropositive patients only 40 (19.9%) presented a reactivation of EBV. Non-early lesions PTLD was diagnosed in ten patients, and early lesions PTLD was diagnosed in five patients. In all cases a positive EBV viral load had been detected at some stage of the follow-up. Having a maximum peak of EBV viral load above the median value observed in the whole cohort (59,909.5 copies/ml) was a significant and independent predictor of non-early lesions PTLD and all PTLD onset. CONCLUSIONS: A high PCR EBV viral load is correlated with the probability of developing PTLD. The definition of a reliable marker is essential to identify patients more at risk of PTLD and to personalize the clinical approach to the single patient.
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