Pneumocystis carinii pneumonia prophylaxis in HIV negative patients with primary CNS lymphoma

Primary central nervous system lymphoma (PCNSL) is an uncommon malignant brain tumor, which is increasing in incidence in immunocompetent individuals. In the recent past, the survival at 5 years was less than 5% when this cancer was treated with radiation therapy and standard chemotherapy. Current high dose methotrexate-based regimens have resulted in median survival of 3-4 years and the 5-year survival approaches 40%. However, these potentially curable patients appear to be at significant risk for developing Pneumocystis carinii pneumonia (PCP), which has a mortality of nearly 50%. The major risk factors in this patient population appear to be glucocorticoids, high dose methotrexate, and radiation therapy all of which reduce CD4+ counts. Prophylaxis must be considered carefully because of the significant risk of drug interactions between the methotrexate and the antibiotics used to prevent Pneumocystis infections. This manuscript reviews the changing therapy for primary CNS lymphomas, the pathogenesis, diagnosis and treatment of P. carinii pneumonia, the potential interactions between methotrexate and prophylactic antibiotics, and the risk of Pneumocystis infection in these patients. It also provides recommendations for Pneumocystis prophylaxis for this patient population.