Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era.

Bay-area Lymphoma Information Network, Tokyo, Japan.
Cancer Science (Impact Factor: 3.48). 11/2011; 103(2):245-51. DOI: 10.1111/j.1349-7006.2011.02139.x
Source: PubMed

ABSTRACT Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B-cell lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15-91 years). We noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2-year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk [RR] 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further.

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    ABSTRACT: Background:Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear.Methods:We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'.Results:Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009).Conclusions:The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.British Journal of Cancer advance online publication, 29 July 2014; doi:10.1038/bjc.2014.405
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    ABSTRACT: Extranodal lymphomas constitute a heterogeneous group of malignancies, accounting for roughly 60% of all non-Hodgkin lymphomas. The extranodal organ where lymphomas arise is an important determining factor of biological, molecular, and aetio-pathogenic features, and of presentation, dissemination pattern, and outcome. An increased risk of CNS involvement, an uncommon but lethal event, has been suggested in some extranodal lymphomas, but the absolute risk is still debatable for most of these malignancies. This debate is because of the presence of selection biases and other confounding factors in related literature, which inevitably has led to conflicting recommendations. The identification of extranodal lymphomas at increased risk of CNS dissemination is an important unmet clinical need; affected patients could benefit from early CNS assessment by neuroimaging and cerebrospinal fluid analysis and adequate CNS prophylaxis, avoiding unnecessary prophylaxis and related toxicity in low-risk patients. This Review discusses relevant confounding factors and identifies high-risk extranodal lymphomas analysing histopathological category, involved organ, and other specific risk factors, which could be helpful for result interpretation and patient stratification in future clinical trials. Finally, a recommendation is provided for CNS-directed management of high-risk extranodal lymphoma patients in daily practice.
    The Lancet Oncology 04/2014; 15(4):e159-e169. · 25.12 Impact Factor
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    ABSTRACT: The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. A CNS prophylaxis is common for Burkitt and B-cell lymphoblastic lymphoma; however, in other NHLs, prophylactic treatments are not systematically warranted. Current risk models showed low sensitivity in predicting CNS involvement, implying overtreatment in roughly 70% of high-risk patients. Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.
    Expert Review of Hematology 10/2013; · 2.38 Impact Factor

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