Patients with high-stage (stage III or stage IV) mature B-lineage non-Hodgkin lymphoma (NHL) (Burkitt or Burkitt-like lymphoma and diffuse large B-cell lymphoma) 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 or Burkitt-like lymphoma or diffuse large B-cell lymphoma) with current therapy in pediatric trials.[1,2,3]
Involvement of the bone marrow may lead to confusion as to whether the patient has lymphoma or leukemia. Traditionally, patients with more than 25% marrow blasts are classified as having mature B-cell leukemia, and those with fewer than 25% marrow blasts are classified as having lymphoma. It is not clear whether these arbitrary definitions are biologically distinct, but there is no question that patients with Burkitt leukemia should be treated with protocols designed for Burkitt lymphoma.[1,3]
Tumor lysis syndrome is often present at diagnosis or after initiation of treatment. This emergent clinical situation should be anticipated and addressed before treatment is started. (Refer to the Tumor lysis syndrome subsection in the Treatment Option Overview section of this summary for more information.) For reduction of the complications of tumor lysis syndrome, current treatment regimens use a prophase of reduced intensity to cytoreduce patients;[1,2,3] however, this does not obviate the use of hyperhydration and allopurinol or rasburicase (urate oxidase). Hyperuricemia and tumor lysis syndrome, particularly when associated with ureteral obstruction, frequently result in life-threatening complications. Gastrointestinal bleeding, obstruction, and (rarely) perforation may occur. Patients with NHL should be managed only in institutions having pediatric tertiary care facilities.
In the NHL-BFM-95 trial, it was shown that when the dose of methotrexate was reduced for R1 and R2 patients, outcome was not inferior; however, reducing the infusion time of methotrexate from 24 hours to 4 hours for R3 and R4 group patients resulted in less mucositis, but inferior outcome. Event-free survival (EFS) with best therapy in NHL-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 CNS disease at presentation (70% 3-year EFS). In the COG-C5961 (FAB/LMB-96) study, 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 therapy. The 3-year EFS was 98% for stage I/II, 90% for stage III, and 86% for stage IV (CNS-negative) patients, while patients with primary mediastinal B-cell lymphoma had a 3-year EFS of 70%. In group C patients, reduction in cumulative dose of therapy and number of maintenance cycles resulted in inferior outcome. 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. 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%. Both the Berlin-Frankfurt-Munster (BFM) and FAB/LMB studies demonstrated that omission of craniospinal irradiation, even in patients presenting with CNS disease, does not affect outcome (COG-C5961 [FAB/LMB-96] and NHL-BFM-90 [GER-GPOH-NHL-BFM-90]).[1,2,3,5]