Viral load of EBV DNAemia is a predictor of EBV-related post-transplant lymphoproliferative disorders in pediatric renal transplant recipients

Pediatr Nephrol. 2017 Aug;32(8):1433-1442. doi: 10.1007/s00467-017-3627-2. Epub 2017 Mar 9.

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.

Keywords: Children; Epstein–Barr virus; Post-transplant lymphoproliferative disorder; Renal transplant; Viral load.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • DNA, Viral / blood*
  • DNA, Viral / isolation & purification
  • Epstein-Barr Virus Infections / blood*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Follow-Up Studies
  • Herpesvirus 4, Human / isolation & purification
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Infant
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Lymphoproliferative Disorders / blood*
  • Lymphoproliferative Disorders / virology
  • Male
  • Postoperative Complications / blood
  • Postoperative Complications / virology
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Transplant Recipients
  • Viral Load*
  • Young Adult

Substances

  • DNA, Viral