In childhood mature B-NHL with CNS disease, patients with blasts in cerebrospinal fluid are at higher risk of failure

To identify the factors influencing outcome in childhood mature B-cell non-Hodgkin lymphoma and acute leukemia (B-NHL/AL) with central nervous system (CNS) disease (CNS+), we analyzed patients <18 years with newly diagnosed B-NHL/AL registered in 3 Lymphomes Malins B studies in France between 1989 to 2011. CNS+ was diagnosed on fulfillment of ≥1 of the following criteria: any L3 cerebrospinal fluid (CSF) blasts (CSF+), cranial nerve palsy, isolated intracerebral mass but also clinical spinal cord compression, and cranial or spinal parameningeal extension. Two hundred seventeen out of 1690 patients (12.8%) were CNS+. CNS+ was significantly associated with male gender, head/neck locations, Burkitt histology, high initial lactate dehydrogenase (LDH) level, and bone marrow involvement. CSF+ was the most frequent pattern of CNS+ (45%). For the 217 CNS+ patients, the 5-year event-free survival (EFS) and overall survival rates (95% confidence interval) were 81.5% (75.8% to 86.1%) and 83.9% (78.4% to 88.2%), respectively. In multivariate analysis, among CNS+ patients, low EFS was associated with CSF+, high initial LDH level, and poor response to cyclophosphamide, oncovin (vincristine), prednisone prephase. These findings have been considered for patient's stratification in the international randomized phase 3 trial Inter-B-NHL-ritux 2010 for children and adolescents with high-risk B-NHL/AL with CNS+ CSF+ patients only receiving intensified chemotherapy.