Transplantation for congenital heart disease is associated with an increased risk of Epstein-Barr virus–related post-transplant lymphoproliferative disorder in children

BACKGROUND
Children undergoing heart transplant are at higher risk of developing post-transplant lymphoproliferative disorder (PTLD) than other solid organ recipients. The factors driving that risk are unclear. This study investigated risk factors for PTLD in children transplanted at 1 of 2 United Kingdom pediatric cardiac transplantation centers.
METHODS
All children (<18 years, n = 200) transplanted at our institution over a 16-year period were analyzed. Freedom from PTLD was assessed using the Kaplan-Meier method and Cox proportional regression.
RESULTS
PTLD occurred in 17 of 71 children transplanted for congenital heart disease (CHD) and 18 of 129 transplanted for acquired cardiomyopathy (ACM). The cumulative incidence of all PTLD was 21.1% at 5 years after transplant. Median time from transplant to PTLD was 2.9 years (interquartile range: 0.9–4.6). Negative Epstein-Barr virus (EBV) serostatus pre-transplant (adjusted hazard ratio [HR]: 2.7, 95% CI: 1.3–5.6, p = 0.01) and underlying CHD (adjusted HR: 3.2, 95% CI: 1.4–7.4, p = 0.007) were independently associated with higher risk of PTLD. Age at thymectomy was significantly different between children with CHD and ACM (0.4 vs 5.5 years, p < 0.01). Median CD4+ and CD8+ T lymphocyte counts at 2 years after transplant were significantly lower in children transplanted for CHD vs ACM (CD4+: 391/µl vs 644/µl, p = 0.01; CD8+: 382/µl vs 500/µl, p = 0.01). At 5 years after transplant, those differences persisted among patients who developed PTLD (CD4+, 430/µl vs 963/µl, p < 0.01 and CD8+, 367/µl vs 765/µl, p < 0.01).
CONCLUSION
Underlying CHD is an independent risk factor for PTLD and is associated with a younger age at thymectomy. A persistent association with altered T lymphocyte subsets may contribute to the impaired response to primary EBV infection and increase the risk of PTLD.