Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: A GELA study on 974 patients

Background:Incidence of central nervous system (CNS) recurrencein patients with aggressive non-Hodgkin's lymphoma who did not receivemeningeal prophylaxis is about 5%. Controversy remains regarding riskfactors associated with such an event preventing a rational approach ofprophylactic strategies.Patients and methods:We analyzed a cohort of 974 patients withaggressive lymphoma in complete remission (CR). All the patients received aCNS prophylaxis consisting of intrathecal injections and intravenous high-dosemethotrexate. The risk repartition on the basis of the internationalprognostic index (IPI) of these 974 CR-patients was low (L): 41%,low-intermediate (LI): 27%, high-intermediate (HI): 19%, high(H): 13%.Results:The incidence of isolated CNS relapse was 1.6%.In a first multivariate logistic regression analysis an increased LDH (P= 0.05, RR = 5) and the presence of more than one extranodal site (P= 0.05, RR = 3) were identified as independent risk factors for isolatedCNS relapse. Another multivariate analysis incorporating IPI as a uniqueparameter showed that only IPI remained significantly associated with a higherrisk of CNS relapse (L–LI: 0.6% vs. HI–H: 4.1%,P= 0.002; RR = 7).Conclusion:Prophylaxis notably reduces the risk of CNS recurrencein the higher risk patients. By contrast, we propose the deletion ofprophylactic intrathecal injections in the lower risk patients.