Primary central nervous system lymphomas

Primary central nervous system lymphoma (PCNSL) is an aggressive B cell lymphoma that occurs in immunocompetent and immunosuppressed patients. Primary ocular lymphoma represents an important variant of this disease. The outcome for patients with PCNSL is rapidly improving with new treatment strategies. This review focuses on recent advances, investigations, and controversies in the management of these increasingly important malignancies.

The incidence of PCNSL is rising in immunocompetent patients over the age of 60 years for unexplained reasons. However, the incidence of AIDS-related PCNSL, which is related to Epstein-Barr virus infections, has fallen with the institution of highly active antiretroviral therapy. During the past decade, standard therapy has evolved from cranial irradiation to high dose methotrexate-based regimens. This shift in therapy has been associated with an increase in the median survival of patients from 1 year to longer than 3 years, and with an equally striking reduction in neurotoxicity if whole brain radiation is avoided. Optimal therapeutic results require careful attention to opportunistic infections, thromboembolic disease, and renal toxicities associated with high dose methotrexate.

Overall, PCNSLs are increasing in frequency and the results of therapy for this disease have dramatically improved during the past decade. Many important therapeutic questions remain unanswered. These include the optimal dose, frequency, and duration of methotrexate, as well as the roles of additional systemic chemotherapy drugs, intrathecal therapy, and cranial irradiation. Further progress in this uncommon disease will depend on entering patients into carefully designed multicenter clinical trials to build upon the significant advances that have been made.