Successful Use of Rituximab To Treat Central Nervous System Lymphoma in a Patient with B-Cell Post-Transplant Lymphoproliferative Disorder (PTLD).

A 27 year old male with end-stage renal failure secondary to IgA nephropathy received a living related renal transplant in 10/2002, complicated by severe cellular and humoral rejection. Immunosuppression included steroids, OKT3, cyclosporine A, rapamycin, thymoglobulin, antithymocyte globulin, and plasmapheresis. He developed multiple complications including severe pancytopenia, pleural effusions, Pseudomonas sepsis, and Vancomycin resistant enterococcus cystitis. Transplant nephrectomy was required 2/2003 for intractable rejection with blood clots in the urine, revealing large nodules of monomorphous B-cell PTLD throughout the renal parenchyma, along with type 2 acute cellular rejection. The B-cells were CD20 positive, and in situ hybridization for EBER was positive in the majority of the cells. PTLD staging was negative in other sites including brain and bone marrow. All immunosuppression was discontinued shortly following the nephrectomy, and he was placed on acyclovir for 3 months until he developed progressive cytopenias. In 8/2003 he underwent open brain biopsy following 2 grand mal seizures and an MRI showing multiple bilateral nonenhancing cortical and subcortical lesions up to several centimeters, with enhancing right temporal and parietal lesions with surrounding vasogenic edema and regional mass effect. Right temporal lobe biospy showed extensive high grade monomorphous B-cell PTLD with necrosis and vascular involvement. Lymphoma staging including lumbar puncture was otherwise negative and LDH was normal. He received a brief course of steroids and valacyclovir in the perioperative period. His performance status remained extremely poor, on hemodialysis, and thus he was not considered a good candidate for systemic chemotherapy, brain radiotherapy, or intrathecal chemotherapy. We elected to give a total of 8 courses of rituximab at 375 mg/m² intravenously weekly. Although systemic rituximab does not generally penetrate the central nervous system very well, it was presumed that the blood brain barrier in this patient was broken down due to extensive lymphomatous cerebral disease. By 9/2003 there was improvement in the brain parenchymal lesions, and since 11/2003 there has been complete stabilization of residual involuted nonenhancing lesions. He remains in complete clinical remission, off rituximab for 22 months. This excellent response suggests that systemic rituximab can be an effective treatment in selected cases of PTLD in which extensive brain disease is present.