Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States

Pediatr Transplant. 2024 Jun;28(4):e14763. doi: 10.1111/petr.14763.

Abstract

Background: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis.

Methods: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis.

Results: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01).

Conclusions: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

Keywords: Epstein–Barr virus; PTLD; pediatric transplantation.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Epstein-Barr Virus Infections* / epidemiology
  • Female
  • Herpesvirus 4, Human
  • Humans
  • Infant
  • Lymphoproliferative Disorders* / epidemiology
  • Lymphoproliferative Disorders* / etiology
  • Lymphoproliferative Disorders* / virology
  • Male
  • Organ Transplantation* / adverse effects
  • Postoperative Complications* / epidemiology
  • Postoperative Complications* / etiology
  • Postoperative Complications* / virology
  • Prospective Studies
  • Risk Factors
  • United States / epidemiology
  • Young Adult