Epstein-Barr Virus Predicts Malignancy After Pediatric Heart Transplant, Induction Therapy and Tacrolimus Don't

Ann Thorac Surg. 2022 Nov;114(5):1794-1802. doi: 10.1016/j.athoracsur.2021.08.038. Epub 2021 Sep 23.

Abstract

Background: Patients after heart transplantation are at increased risk for malignancy secondary to immunosuppression and oncogenic viral infections. Most common among children is posttransplant lymphoproliferative disorder (PTLD), occurring in 5% to 10% of patients. We used a national database to examine the incidence and risk factors for posttransplant malignancy.

Methods: The United Network for Organ Sharing database was queried for pediatric (<18 years) heart transplant recipients from October 1987 through November 2019. Freedom from malignancy after transplant was assessed with Kaplan-Meier analysis. Cox regression was performed to generate hazard ratios (HRs) and 95% CIs for risk of malignancy development.

Results: Of 8581 pediatric heart transplant recipients, malignancy developed in 8.1% over median follow-up time of 6.3 years, with PTLD compromising 86.4% of the diagnosed cancers. The incidence of PTLD development was 1.3% at 1 year and 4.5% at 5 years. Older age at the time of transplant was protective against the development of malignancy (HR, 0.98; 95% CI, 0.96-0.99; P < .001), whereas a history of previous malignancy (HR, 1.9; 95% CI, 1.2-3.0; P = .007) and Ebstein-Barr virus (EBV) recipient-donor mismatch (HR, 1.7; 95% CI, 1.3-2.2; P < .001) increased the risk. Induction therapy, used in 78.9% of the cohort, did not increase malignancy risk (P = .355) nor did use of maintenance tacrolimus (P = .912).

Conclusions: PTLD occurred after 7% of pediatric heart transplants, with risk increased by younger age and EBV mismatch, highlighting the importance of PTLD monitoring in EBV-seronegative recipients. Induction therapy, used in most of the pediatric heart transplants, does not seem to increase posttransplant malignancy nor does tacrolimus, the most commonly used calcineurin inhibitor.

MeSH terms

  • Calcineurin Inhibitors
  • Child
  • Epstein-Barr Virus Infections* / epidemiology
  • Epstein-Barr Virus Infections* / etiology
  • Heart Transplantation* / adverse effects
  • Herpesvirus 4, Human
  • Humans
  • Induction Chemotherapy
  • Lymphoproliferative Disorders* / epidemiology
  • Lymphoproliferative Disorders* / etiology
  • Neoplasms* / epidemiology
  • Neoplasms* / etiology
  • Risk Factors
  • Tacrolimus / adverse effects

Substances

  • Tacrolimus
  • Calcineurin Inhibitors