Patients with disseminated mature B-lineage non-Hodgkin lymphoma (NHL) (Burkitt or Burkitt-like lymphoma and diffuse large B-cell lymphoma [DLBCL]) have an 80% to 90% long-term survival.[1,2,3] Unlike mature B-lineage NHL seen in adults, there is no difference in outcome based on histology (Burkitt, Burkitt-like, or DLBCL) with current therapy in pediatric trials.[1,2,3]

For the Berlin-Frankfurt-Munster (BFM) group, disseminated mature B-lineage NHL defined by R2 is unresected disease or stage III disease with lactate deyhdrogenase (LDH) levels lower than 500 u/L; R3 is stage III disease and LDH concentrations between 500 u/L and 1,000 u/L or leukemic disease (>25% blasts in marrow) with LDH levels lower than 1,000 u/L; R4 is stage III/IV disease or leukemic disease with LDH levels higher than 1,000 u/L and/or central nervous system (CNS) involvement.[1] All patients receive a cytoreductive prophase. R2 group patients receive four cycles of intensive chemotherapy; R3 patients receive five cycles of intensive chemotherapy; and R4 patients receive six cycles of intensive chemotherapy. In the BFM-90 study, it was demonstrated that increasing the dose and duration of infusion (24 hours) of methotrexate resulted in an improved outcome.[4] In the BFM-95 trial, it was shown that reducing the infusion time of methotrexate from 24 hours to 4 hours resulted in inferior outcome for R3 and R4 group patients.[1] Event-free survival (EFS) with best therapy in BFM-95 was more than 95% for R1 and R2 group patients and was 93% for R3 and R4 group patients. Inferior outcome was observed for patients with primary mediastinal B-cell lymphoma (50% 3-year EFS) and central nervous system (CNS) disease at presentation (70% 3-year EFS).[4] In the FAB/LMB-96 study, group B consists of all patients (stage I-IV) with unresected disease but excludes those with leukemic (>25% marrow involvement) and/or CNS involvement, while group C patients have leukemic and/or marrow involvement.[2,3] The outcome of group B patients, who had a greater than 20% response to cytoreductive prophase, was not affected by a reduction of the total dose of cyclophosphamide by 50% and elimination of one cycle of maintenance.[2] The 3-year EFS was 98%, 90%, and 86% for stage I/II, stage III, and stage IV (CNS-negative) patients, respectively, while patients with primary mediastinal B-cell lymphoma had a 3-year EFS of 70%.[2] In group C patients, reduction of therapy resulted in inferior outcome.[3] Patients with leukemic disease only, and no CNS disease, had a 3-year EFS of 90%, while patients with CNS disease at presentation had a 70% 3-year EFS.[3] This study identified response to prophase reduction as the most significant prognostic factor, with poor responders (i.e., <20% resolution of disease) having an EFS of 30%.[3] Both the BFM and FAB/LMB studies demonstrated that omission of craniospinal irradiation, even in patients presenting with CNS disease, does not affect outcome (FAB/LMB96, NHL-BFM 90).[1,2,3,4]