Treatment of EBV-associated T cell post-transplant lymphoproliferative disorder with CNS involvement in a pediatric solid-organ transplant patient

Abstract

9040 Background: Post-transplant lymphoproliferative disorder (PTLD) is a known complication of immunosuppression following solid organ and stem cell transplantation. It ranges from benign lymphoid hyperplasia to fulminant systemic disease with high mortality. Most cases are B lineage and associated with Epstein-Barr virus (EBV+). T cell PTLD is rare and usually EBV negative. To date only 5 cases of EBV+ T cell PTLD have been reported in pediatric patients and none have had documented involvement of the central nervous system (CNS). Methods: We provide clinical, histologic, immunophenotypic and molecular details of a case of fulminant EBV+ T cell PTLD with CNS involvement and compare our data to the clinical presentations, biology and outcomes of the other reported cases of pediatric T cell PTLD (these include 5 EBV+ CNS− cases, 3 EBV− CNS+ cases, and 4 EBV− CNS− cases with dissemination or marrow involvement). Results: A 4.5 year old male developed EBV+ T cell PTLD with CNS involvement 3 years following a cadaveric renal transplantation. His fulminant presentation included fever, hypotension, splenomegaly, pancytopenia, coagulopathy, and bilateral pleural effusions. He had lymphocytosis in his CSF and his MRI showed brain white matter changes consistent with leukoencephalopathy. T lineage was confirmed by the presence of T cell markers CD3, 5, 7, 45 and TCRγ. The presence of EBV was demonstrated by in situ hybridization for EBER. His treatment followed the Children’s Oncology Group protocol A5971 for disseminated lymphoblastic lymphoma that employs a standard NHL/BFM-95 regimen with cyclophosphamide and anthracycline intensification during the induction and delayed intensification phases with a treatment duration of 2 years. He has received no irradiation. After 16 months, he has no measurable disease. Conclusions: EBV+ T cell PTLD is extremely rare in pediatrics and has resulted in mortality in 12 of 17 reported cases. This is the first report of EBV+ T cell PTLD with CNS involvement in a pediatric patient. Although no standardized treatment exists, the fulminant presentation, T lineage disease, and CNS involvement warranted aggressive systemic and intrathecal chemotherapy. No significant financial relationships to disclose.