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

Abstract EN

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.