Prevention of central nervous system relapses in diffuse large B-cell lymphoma: which patients and how?

This review analyzes most recent data on the risk of central nervous system (CNS) dissemination and the efficacy of current strategies for CNS prophylaxis in diffuse large B-cell lymphoma (DLBCL).

CNS dissemination still remains a rare but usually fatal complication of DLBCL. Although risk models for CNS involvement in DLBCL have been postulated on the basis of clinical findings such as more than one extranodal site, Eastern Cooperative Oncology Group performance status greater than 1, lactate dehydrogenase elevation in serum, B-symptoms, high international prognostic index score and involvement of specific sites their predictive value is relatively low. The choice of drugs and time-point for prophylaxis still remain to be defined; however, there is some evidence supporting the role of systemic CNS-penetrating chemotherapy, in particular high-dose methotrexate (>1 g/m) in the early course of disease. A role for systemic rituximab has been postulated, however, with ambiguous results among studies.

Better identification of risk factors and disease variables associated with CNS involvement in DLBCL including biological and molecular parameters is urgently needed to reduce CNS recurrences through a well designed prophylaxis regimen and to avoid unnecessary intensive and toxic treatments.