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Ann Oncol. 2012 May;23(5):1267-73. doi: 10.1093/annonc/mdr440. Epub 2011 Oct 11.

CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group.

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Department of Hematology, Oncology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Hamburg, Germany.



To describe incidence, risk factors, and influence of treatment on occurrence of central nervous system (CNS) relapse or progression in younger patients with aggressive B-cell lymphoma.


We analyzed 2210 patients with aggressive B-cell lymphoma treated on various studies for CNS relapse/progression. Treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) ± etoposide. Six hundred and twenty patients also received rituximab. CNS prophylaxis was intrathecal methotrexate on High-CHOEP and MegaCHOEP phase III studies if upper neck, head, bone marrow, or testes were involved.


Fifty-six of 2196 patients (2.6%) developed CNS disease. It occurred early (median 7.0 months), median survival was 5.0 months. Patients with age-adjusted International Prognostic Index (aaIPI) 0 or 1 treated with rituximab showed a low risk for CNS disease (2-year rates: 0% or 0.5%), and rituximab decreased the risk (relative risk 0.3, 95% confidence interval 0.1-0.9, P = 0.029). Patients with aaIPI 2 or 3 showed a moderate risk (4.2%-9.7%) and no significant reduction of CNS disease with rituximab. CNS prophylaxis was of no significant benefit.


In younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment.

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