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Primary CNS lymphoma in immunocompetent patients.

Primary central nervous system lymphoma (PCNSL) constitutes a rare group of extranodal non-Hodgkin's lymphomas (NHLs), primarily of B cell origin, whose incidence has markedly increased in the last three decades. Immunodeficiency is the main risk factor, but the large majority of patients are immunocompetent. Recent evidence suggests a specific tumorigenesis that may explain their particular clinical behavior compared with systemic NHL. The addition of i.v. high-dose methotrexate (MTX) chemotherapy to whole-brain radiotherapy (WBRT) has considerably improved the prognosis, leading to a threefold longer median survival time compared with WBRT alone and represents the current standard of care. However, this combined treatment exposes the patient, especially the elderly, to a high risk for delayed neurotoxicity. In the older population (>60 years), there is growing evidence that MTX-based chemotherapy alone as initial treatment is the best approach to achieve effective tumor control without compromising patient quality of life. In the younger population, the risk for neurotoxicity is much lower, and this strategy is controversial because it may be associated with higher relapse rates. Future efforts should focus on the development of new polychemotherapy regimens allowing the reduction or deferral of WBRT in order to minimize the risk for delayed neurotoxicity. In this setting, intensive chemotherapy with autologous blood stem cell transplantation was recently demonstrated to be feasible and efficient as salvage therapy and is currently being evaluated as part of primary treatment. This review highlights the recent advances in the pathogenesis and treatment of PCNSL in the immunocompetent population.