A 16-Year Multi-Institutional Study of the Role of Age and EBV Status on PTLD Incidence Among Pediatric Heart Transplant Recipients

Abstract

The objective was to determine the incidence and hazard for posttransplant lymphoproliferative disease (PTLD) in a study of 3170 pediatric primary heart transplants between 1993 and 2009 at 35 institutions in the Pediatric Heart Transplant Study. 147 of 151 reported malignancy events were classified as PTLD. Overall freedom from PTLD was 98.5% at 1 year, 94% at 5 years and 90% at 10 years. Freedom from PTLD was lowest in children (ages 1 to < 10 years) versus infants (<1 year) and adolescents (10 to < 18 years) with children at highest risk for PTLD with a relative risk of 2.4 compared to infants and 1.7 compared to adolescents. Positive donor EBV status was a strong risk factor for PTLD in the seronegative recipient, but risk magnitude was dependent on recipient age at the time of transplantation. Nearly 25% of EBV seronegative recipients of EBV+ donors at ages 4-7 at transplantation developed some form of PTLD. The overall risk for PTLD declined in the most recent transplant era (2001-2009, p = 0.003). These findings indicate that EBV status and the age of the recipient at the time of transplantation are important variables in the development of PTLD in the pediatric heart transplant recipient.

Neonatal heart transplantation

“…Most cases are related to EBV infection. The incidence of PTLD is about 10% at 10 years in pediatric recipients (27). In our series of infant (0-12 months) heart transplants, a 22 percent actuarial risk of PTLD was observed at 25 years (6).…”

“…There is a strong effect of age on development of PTLD. Young infants and older children (>10 years) have a lower incidence of PTLD compared to young children (1-10 years) (27). The protective influence of maternal antibodies in infants may help explain this finding.…”

Have risk factors for mortality after heart transplantation changed over time? Insights from 19 years of Cardiac Transplant Research Database study

“…Such adjustments are not without risk, particularly in younger patients, who are at higher risk for malignancies, particularly post-transplant lymphoproliferative disease. 23 Nonetheless, among younger recipients, there remains considerable room for improvement in 5-year survival.…”

In vivo intratumoral Epstein–Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications

“…25,26 Moreover, prophylactic antiviral therapies are effective in preventing posttransplant lymphomas, particularly in children, highlighting the role of primary EBV infection or EBV reactivation in their development. 19,20,27 During primary EBV infection and EBV reactivation, active viral replication occurs. 28 Viral replication is the hallmark of the lytic phase and EBV replication has an important role in lymphomagenesis.…”