Clinical Characteristic and Prognosis of Post-Transplant Lymphoproliferative Disorder in Pediatric Heart Transplant Recipients in Japan

Purpose: Post-transplant lymphoproliferative disorder (PTLD) caused by Epstein-Barr virus (EBV) has recently has been recognized as a serious complication of various organ transplantations. In our institute, we have followed-up 34 pediatric patients after heart transplantation. We retrospectively investigated clinical features of PTLD in heart transplant recipients.

Methods: The evaluation period was from July 2004 to June 2015. Six patients with PTLD (4 boys, 2 girls) were diagnosed by blood examination, lymph node histology and EBV viral load in peripheral blood and invasive organ.

Results: Median age at onset of PTLD was 4.5 years old (range, 3.2-16.2 years). Median time from transplantation to onset was 18 months (range, 7-45 months). Bone marrow and central nervous system invasion were not detected in all cases. Four patients were EBV-seronegative recipients for EBV-seropositive donors. We performed the lymphoma-based chemotherapy combined with the anti-CD20 monoclonal antibody rituximab and achieved remission. As a result, five patients remained alive in remission, and one patient died of therapy-related toxicity. Although one patient relapsed after chemotherapy, she achieved second remission after multimodal chemotherapy combined with rituximab. Abdominal lymph node involvement was detected in four cases, and one patient experienced severe abdominal symptoms including intestinal perforation.

Conclusion: EBV serostatus and the period from transplantation to onset of PTLD appear to represent important prognostic factors. Early detection followed by pre-emptive reduction of immunosuppressive agents is essential to the management of PTLD, but may increase the risk of fatal rejection. We administered chemotherapy combined with rituximab, and this treatment strategy might be effective. However, severe fatal toxicity developed in one patient, and severe abdominal symptoms due to tumor lysis were noted in many cases. These findings suggested the importance of carefully selecting the induction treatment and perform various supportive therapies. We should establish appropriate treatment strategies according to prognostic factors because of the distinctive characteristics of PTLD by accumulating more cases.