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Lymphomatous meningitis: prophylaxis and treatment Volume 14, issue 4, Juillet-août 2008

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Authors
Institut Jules Bordet, Université Libre de Bruxelles (ULB), Belgique

Central nervous system (CNS) involvement is a dreadful complication in high-grade non-Hodgkin’s lymphomas (NHL). It occurs most often in the context of relapsing disease.Since most cases are incurable and the outcome of lymphomatous meningitis is rapidly fatal, identification of patients at high risk for CNS involvement is essential, in order to undertake optimal prophylactic measures. Incidence of lymphomatous meningitis varies from 2.8% in low-grade NHL to 24.4% in high-grade tumors. Reporting a GELA study, C. Haioun showed that the incidence of CNS involvement after prophylaxis is 1.6% compared to 5% without prohylaxis. Diagnosis is established on imaging studies (gadolinium-enhanced magnetic resonance) and identification of lymphomatous cells in the cerebrospinal fluid (CSF), which is based on morphology and flow cytometry.Published risk factors for the development of lymphomatous meningitis are stage of disease at presentation, and other known prognostic factors (according to the International Prognostic Index [IPI]) such as lactate dehydrogenase (LDH) level and number of extranodal sites. We suggest an evidence-based prophylactic attitude: patients presenting with high-grade NHL, and more than two age-adjusted IPI adverse factors or specific extranodal localizations (sinuses, testicles) must be given optimal prophylaxis, which consists in intrathecal and high-dose systemic chemotherapy. Concerning treatment of lymphomatous meningitis, the goals are improvement in quality of life without excessive side effects. Radiotherapy is advised in symptomatic patients in order to delay the progression of neurological symptoms, but has no impact on survival. High-dose systemic chemotherapy using CNS-active drugs shows encouraging results particularly when followed by intensification and autologous stem cell transplantation.Intrathecal chemotherapy is also part of the treatment schemes. Commonly used drugs are methotrexate, cytarabine and recently-approved DepoCyt ®, which is a sustained-release form of cytarabine using a liposomal formulation.Further trials are warranted in order to compare this new agent to methotrexate and regular cytarabine, and to prospectively evaluate curative (and no longer palliative) approaches.