title: Viral load of EBV DNAemia is a predictor of EBV-related post-transplant lymphoproliferative disorders in pediatric renal transplant recipients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Colombini
authors.affiliation: Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Guzzo
authors.affiliation: Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Morolli
authors.affiliation: Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Pediatrics, University of Padova, Padova, Italy.
authors.forename: Germana
authors.initials: G
authors.lastname: Longo
authors.affiliation: Virology Unit, Bambino Gesù Children's Research Hospital-IRCCS, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Russo
authors.affiliation: Hematology and Oncology, Bambino Gesù Children's Research Hospital-RCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lombardi
authors.affiliation: Hematology and Oncology, Bambino Gesù Children's Research Hospital-RCCS, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.affiliation: Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Pediatrics, University of Padova, Padova, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.affiliation: Unit of Clinical Epidemiology, Bambino Gesù Children's Research Hospital-IRCCS, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Piga
authors.affiliation: Unit of Clinical Epidemiology, Bambino Gesù Children's Research Hospital-IRCCS, Rome, Italy.
authors.forename: Marta Luisa
authors.initials: ML
authors.lastname: Ciofi Degli Atti
authors.affiliation: Hematology and Oncology, Bambino Gesù Children's Research Hospital-RCCS, Rome, Italy.|University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy. luca.dellostrologo@opbg.net.
authors.forename: Luca
authors.initials: L
authors.lastname: Dello Strologo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood* / Q000302:isolation & purification; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007223:Infant; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000097:blood* / Q000821:virology; D008297:Male; D011183:Postoperative Complications / Q000097:blood / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D066027:Transplant Recipients; D019562:Viral Load; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: Children; Epstein–Barr virus; Post-transplant lymphoproliferative disorder; Renal transplant; Viral load