Treatment of Recurrent Posttransplant Lymphoproliferative Disorder of the Central Nervous System with High-Dose Methotrexate

Posttransplant lymphoproliferative disorder (PTLD) is a frequent complication of intestinal transplantation and is associated with a poor prognosis. There is currently no consensus on optimal therapy. Recurrent PTLD involving the central nervous system (CNS) represents a particularly difficult therapeutic challenge. We report the successful treatment of CNS PTLD in a pediatric patient after liver/small bowel transplantation. Initial immunosuppression (IS) was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil. EBV viremia developed 8 weeks posttransplantation, and despite treatment with cytogam and valganciclovir the patient developed a polymorphic, CD20+, EBV+ PTLD with peripheral lymphadenopathy. Following treatment with rituximab, the lymphadenopathy resolved, but a new monomorphic CD20？, EBV+, lambda-restricted, plasmacytoid PTLD mesenteric mass emerged. Complete response of this PTLD was achieved with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, 4 months off therapy he developed CNS PTLD (monomorphic CD20？, EBV+, lambda-restricted, plasmacytoid PTLD) of the brain and spine. IS was discontinued and HD-MTX (2.5–5？gm/m2/dose) followed by intrathecal HD-MTX (2？mg/dose ×2-3 days Q 7–10 days per cycle) was administered Q 4–7 weeks. After 3 cycles of HD-MTX, the CSF was negative for malignant cells, MRI of head/spine showed near-complete response, and PET/CT was negative. The patient remains in complete remission now for 3.5 years after completion of systemic and intrathecal chemotherapy. Conclusion. HD-MTX is an effective therapy for CNS PTLD and recurrent PTLD that have failed rituximab and CHOP chemotherapy. 1. Introduction PTLD of the CNS is a rare complication of solid organ transplantation (SOT) and there is currently no consensus on optimal therapy. Recurrent PTLD following rituximab and front-line chemotherapy represents a particularly difficult therapeutic challenge. We report the successful use of HD-MTX and intrathecal MTX to treat recurrent PTLD of the CNS in pediatric patient status after combined liver/small bowel transplantation. 2. Case Report Our patient underwent combined liver/small bowel transplantation at the age of 15 months for short bowel syndrome secondary to ileal atresia and TPN-associated liver disease. Donor and recipient were both CMV and EBV seronegative. Immunosuppression (IS) was with thymoglobulin, solucortef, tacrolimus, and mycophenolate mofetil (MMF). MMF was discontinued after two weeks due to increased ostomy output. EBV viremia developed at 8