Predictors of central nervous system involvement in diffuse large B-cell lymphoma: a divining rod is wanted

In the last decades, our knowledge on the management of diffuse large B-cell lymphomas (DLBCL) has expanded remarkably. Nevertheless, some important questions, like the impact of dose dense chemotherapy, the role of consolidation radiotherapy, the selection of the best candidates for new target drugs, the optimal management for patients with high International Prognostic Index (IPI) scores and the prevention of central nervous system (CNS) relapse, remain unanswered. CNS dissemination is a rare but fatal event in DLBCL. It is more common in highly aggressive lymphomas, such as Burkitt's and lymphoblastic lymphomas, but DLBCL patients with intermediate-high IPI and advanced disease and/or affected by some forms of extranodal lymphomas are usually retained at high risk of CNS dissemination. However, predicting variables and scores have low sensitivity, identifying only ≈25% of high-risk patients (1,2). In these studies, CNS prophylaxis is variably indicated, following unclear definition of high-risk patients and using often ineffective strategies. Moreover, studies are invariably undersized since the CNS relapse rate in DLBCL is near 5-6%; this small number of events would require thousands of cases to draw reliable conclusions, especially to accurately assess the risk of CNS in DLBCL arising primarily in different extranodal sites. Last but not least, available predictive scores were established in the pre-rituximab era, which is a relevant interpretation bias as this antibody has changed the natural history of DLBCL and seems to be associated with a reduction of CNS recurrence risk (3,4). In this issue of the Revista Brasileira de Hematologia e Hemoterapia, da Rocha et al. report their efforts to identify reliable variables predicting CNS recurrence in a retrospective series of 133 patients with DLBCL diagnosed between 2001 and 2008 (5). Accordingly, male gender, previous use of intrathecal chemotherapy and refractory response to the initial treatment were independent risk factors for CNS infiltration. The authors should be commended for the effort to analyze all this bulk of data to identify risk predictors. The intrinsic value of this study is evident if we compare these observations with prior studies in this field. Patients' characteristics, CNS relapse rates, and survival figures are very similar to those previously reported. At the same time, this study exhibits most of the major limitations of the previous articles, which are directly related to the small numbers of events (CNS relapses) and investigated patients. In particular, denominators of some subgroups are really small; for instance, only five patients had involvement …