Successful Treatment of Central Nervous System Post-Transplant Lymphoproliferative Disease With a Reduced Dose of High-Dose Methotrexate

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Post-transplant lymphoproliferative disease (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation that occurs as a result of immunosuppression. PTLD isolated to the central nervous system (CNS) is a rare disease and it presents with nonspecific signs and symptoms. Optimal therapy guidelines have not yet been established for CNS PTLD. Here, we report a case of successful treatment of CNS PTLD in an adult female following two subsequent kidney transplants. Initial management was with immunosuppression reduction and a trial of rituximab. There were concerns regarding using methotrexate (MTX) given the patient's fragile transplant status. Magnetic resonance imaging of the brain following four cycles of rituximab revealed the progression of the disease. Subsequently, high-dose MTX (HD-MTX) was considered within the constraints of potential kidney toxicities given her transplant status and chronic kidney disease. Potential toxicities from other therapies, such as brain radiation, also factored into the final decision. The patient was treated with one cycle of a combination of rituximab and HD-MTX 1 g/m2. The patient tolerated HD-MTX and did not have evidence of renal toxicity in laboratory studies. Following that, she was started on a reduced dose of HD-MTX at 2 g/m2 every two weeks instead of the higher MTX dose range of 3.5 to 8 g/m2, which was a shared decision with the patient and nephrology after weighing the risk of kidney dysfunction with the possibility of a less than optimal response with regards to her lymphoma. She was followed with a magnetic resonance imaging of the brain, which demonstrated a complete response after four cycles. Further consolidation treatments with HD-MTX 2 g/m2 every four weeks were administered to complete one year of treatment. Following the completion of chemotherapy, the patient was able to achieve and maintain a complete response without affecting her kidney function. She continues to do well one year following treatment. This case highlights the significance of tailoring therapy to each individual based on their comorbidities and clinical response, as well as the possible merit in exploring the use of a reduced dose of HD-MTX in the treatment of CNS PTLD in patients at high risk for renal toxicity.

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