EBV Predicts Post-Pediatric Heart Transplant Malignancy; Induction Therapy and Tacrolimus Don't.

BACKGROUND: Patients after heart transplantation are at increased risk for malignancy secondary to immunosuppression and oncogenic viral infections. Most common amongst children is post-transplant lymphoproliferative disorder (PTLD), occurring in 5-10% of patients. We utilized a national database to examine incidence and risk factors for post-transplant malignancy.

METHODS: The United Network for Organ Sharing (UNOS) database was queried for pediatric (<18 years) heart transplant recipients from 10/1987-10/2019. Kaplan-Meier analysis was performed to assess freedom from malignancy post-transplant. Cox regression was performed to generate hazard ratios (HR [95% CI]) for risk of malignancy development.

RESULTS: Of 8,581 pediatric heart transplant recipients, 8.1% developed malignancy over median follow-up time of 6.3 years, with PTLD compromising the majority (86.4%) of diagnosed cancers. The incidence of PTLD development was 1.3% and 4.5% at one and five years. Older age at the time of transplant was protective against the development of malignancy (HR 0.98 [0.96-0.99], p<0.001), whereas a history of previous malignancy (HR 1.9 [1.2-3.0], p=0.007) and Ebstein-Barr virus (EBV) recipient-donor mismatch (HR 1.7 [1.3-2.2], p<0.001) increased the risk. Use of induction therapy (utilized in 78.9% of the cohort) did not increase malignancy risk (p=0.355); nor did use of maintenance tacrolimus (p=0.912).

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, utilized in the majority of pediatric heart transplants, does not seem to increase post-transplant malignancy, nor does the most commonly used calcineurin inhibitor tacrolimus.