Risk factors for post-transplant lymphoproliferative disorder in pediatric patients: a case-control study

Upton D Allen1, Gabrielle Farkas, Diane Hébert

  • 1Division of Infectious Diseases, The Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada. upton.allen@sickkids.ca

Insights

Post-transplant lymphoproliferative disorder (PTLD) is a risk after pediatric transplants. Higher Epstein-Barr Virus (EBV) loads increase PTLD likelihood, even in EBV-seropositive recipients, indicating broader risk factors beyond initial serostatus.

Area of Science:

  • Pediatric Transplantation
  • Virology
  • Immunology

Background:

  • Post-transplant lymphoproliferative disorder (PTLD) is a significant complication following pediatric organ transplantation.
  • Epstein-Barr Virus (EBV) is a primary driver of PTLD, with EBV-seronegative recipients of EBV-seropositive organs being at highest risk.
  • However, risk factors among EBV-seropositive recipients remain less defined.

Purpose of the Study:

  • To investigate risk factors for PTLD in pediatric transplant recipients.
  • To compare clinical, virologic, and immunosuppressive profiles of PTLD cases and controls.
  • To identify specific patient groups, including EBV-seropositive recipients, at risk for PTLD.

Main Methods:

  • A case-control study design was employed, matching PTLD cases with two controls based on organ type and transplant period.
  • Biopsy-proven PTLD cases were identified over a four-year period (1997-2000).
  • Clinical, virologic (including EBV viral load), and immunosuppressive data were compared between cases and controls.

Main Results:

  • Twenty-two PTLD cases were diagnosed, occurring at a median of 22.8 months post-transplantation.
  • PTLD cases exhibited significantly higher mean baseline EBV loads compared to controls (3.1 log(10) vs. 1.6 log(10)/10^6 PBMCs).
  • Each log increase in EBV viral load correlated with a threefold increase in PTLD risk. Approximately 25% of PTLD cases occurred in EBV-seropositive recipients, who tended to be older and had a worse prognosis.

Conclusions:

  • Elevated Epstein-Barr Virus (EBV) viral load is a critical risk factor for PTLD in pediatric transplant recipients.
  • PTLD occurs not only in EBV-seronegative recipients of EBV-seropositive organs but also in a significant proportion of EBV-seropositive recipients, suggesting broader risk factors.
  • Further research is needed to fully elucidate the factors contributing to PTLD development in EBV-seropositive pediatric transplant patients.