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Initial treatmentIn each of the three studies, patients were assigned to one of three treatment groups (A, B and C) based on the stage of initial disease, 2,3,5,6 and received two (group A), four or five (group B), or eight (group C) courses of chemotherapy. Rituximab was not used in initial treatment. Group A patients (completely resected stage I and abdominal stage II) did not receive central nervous system (CNS) prophylaxis (no intrathecal treatment, no HD methotrexate). Patients in group C (stage IV with CNS involvement and B-AL) received HD methotrexate at a dose of 8 g/m 2 , and consolidation courses which consisted of HD cytarabine and etoposide (CYVE). In group B (all patients not in group A or group C), patients received HD methotrexate at a dose of 3 g/m 2 and cytarabine in a 5-day continuous infusion during consolidation. Group B patients were switched to group C if tumor regression was less than 20% 7 days after the pre-phase COP (cyclophosphamide, oncovin, and prednisone), or if complete remission was not achieved after the first course of consolidation. There were only minor differences among the three studies, allowing the results to be combined and analyzed (see Online Supplementary Material). Recommendations for treatment of relapseAlthough there was no prospective trial for treatment of relapse within the LMB protocols, there were general therapeutic recommendations. The first one was to obtain a second complete remission with salvage chemotherapy, based on the previous therapy: group C therapy/CYVE course for group A patients, and CYVE courses for group B patients. Salvage chemotherapy was more heterogeneous for patients who had already received group C therapy (initially or after switching from group B), depending on the time period of the study and the type of relapse: most patients underwent therapy with VENOMID (vindesine, novantrone, methylprednisolone, ifosfamide), ICN (ifosfamide, carboplatin and novantrone) or ICE (ifosfamide, carboplatin, etoposide, and triple intrathecal therapy). Treatment recommended for CNS relapse was two weekly courses of HD methotrexate (8 or 12 g/m 2 as 24-hour infusions), with intrathecal therapy, potentially followed by another chemotherapy regimen.The second recommendation was to consolidate the second complete remission with HD chemotherapy and autologous HSCT. The HD chemotherapy was most often either BEAM (BCNU, VP-16, aracytine and melphalan) or BAM (busulfan, aracytine, and melphalan), depending on the histology, time period of the study, and type of relapse. However, some investigators preferred total body irradiation-containing regimens with allogeneic HSCT. The anti-CD20 monoclonal antibody (rituximab) was added to the salvage chemotherapy for some patients after 1996.Other details on patients, histopathology/immunophenotyping, responses, statistics and HD chemotherapy regimens are presented in the Online Supplementary Methods and Online Supplementary Table SA. Results Patients' initial characteristicsSixty-seven of 1322 patients (5%) (27/5...

Introduction In order to describe relapsed B‐cell non‐Hodgkin lymphoma and mature acute leukemia in children/adolescents treated with the Lymphomes Malins B (LMB) regimen and their outcome in the rituximab era, relapses in the French LMB2001 study were reviewed. Methods Between February 2001 and December 2011, 33 patients out of 773 (4.3%) relapsed; 27 had Burkitt lymphoma and six large B‐cell histology. Median age at diagnosis was 10.1 years. One patient was initially treated in risk group A, 21 in group B, and 11 in group C. Results Median time to relapse after diagnosis was 4.5 months (range 2.4‐13.6). Thirty‐two patients received salvage therapy. Twenty‐seven received rituximab mainly in addition to high‐dose cytarabine and etoposide (n = 18) and/or ifosfamide, carboplatin, and etoposide (n = 7). First‐line salvage chemotherapy response rate was 66% with 47% being complete remission (CR). Twenty‐one patients received high‐dose chemotherapy (HDC) followed by autologous (n = 13) or allogeneic (n = 8) transplant. With a median follow‐up of 6.8 years, the 5‐year survival rate after relapse was 36.4% (95% confidence interval [CI] 22‐53%). Twelve patients were still alive; all but one (group A) received consolidation treatment. Achieving CR before consolidation was significantly associated with better survival, with a 5‐year survival rate of 75% (95% CI 46.8‐91.1%) for patients in CR before HDC, 33% (95% CI 9.7‐70%) for patients in partial remission, and 0% for nonresponders (P = .033). Conclusion Survival of children/adolescents with mature B‐cell lymphoma/leukemia remains poor after relapse with no apparent improvement with rituximab. Response rates to salvage chemo‐immunotherapies are insufficient and new drugs are urgently needed to improve disease control.