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Non-Hodgkin's Lymphoma

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High-Stage Childhood B-cell NHL Treatment


    Rituximab is a mouse/human chimeric monoclonal antibody targeting the CD20 antigen. Among the lymphomas that occur in children, diffuse large B-cell lymphoma and Burkitt lymphoma both express high levels of CD20.[6] Rituximab has been safely combined with standard doxorubicin, cyclophosphamide, vincristine, and prednisone (CHOP) chemotherapy and has been shown to improve outcome in a randomized trial of adults with diffuse large B-cell lymphoma (CAN-NCIC-LY9).[7,8] In an adult study, rituximab has also been safely combined with an intensive chemotherapy regimen used to treat patients with Burkitt lymphoma.[9] In children, a single-agent phase II study of rituximab performed by the BFM group showed activity in Burkitt leukemia and lymphoma.[10][Level of evidence: 2Div] A Children's Oncology Group (COG) pilot study (COG-ANHL01P1) to test the toxicity of adding rituximab to FAB/LMB-96 (COG-C5961) has completed accrual and results are pending.

    Standard Treatment Options

    Current data do not suggest superiority for either of the following standard treatment options.

    Table 5. Standard Treatment Options for High-Stage B-cell NHL

    StratumDisease ManifestationsTreatment
    ALL = acute lymphoblastic leukemia; BFM = Berlin-Frankfurt-Munster; CNS = central nervous system; LDH = lactate dehydrogenase; NHL= non-Hodgkin lymphoma.
    FAB/LMB-96 International Study COG-C5961 (FAB/LMB-96)[2,3]BMultiple extra-abdominal sitesPrephase + four cycles of chemotherapy (reduced intensity arm)[2]
    Nonresected stage I and II, III, IV
    Marrow <25% blasts
    No CNS disease
    CMature B-cell ALL (>25% blasts in marrow) and/or CNS diseasePrephase + eight cycles of chemotherapy (full intensity arm)[3]
    BFM Group[1,5]R2Nonresected stage I/II and stage III with LDH <500 IU/LPrephase + four cycles of chemotherapy (4 h methotrexate infusion)[1]
    R3Stage III with LDH 500–999 IU/LPrephase + five cycles of chemotherapy (24 h methotrexate infusion)[1]
    Stage IV, B-cell ALL (>25% blasts) and LDH <1,000 IU/L
    No CNS disease
    R4Stage III, IV, B-cell ALL with LDH >1,000 IU/LPrephase + six cycles of chemotherapy (24 h methotrexate infusion)[1]
    Any CNS disease

    Treatment Options Under Clinical Evaluation

    The following is an example of a national or international clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

    • COG-ANHL1131 (Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III–IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia): This randomized study of patients with high-risk disease (defined as Group B with high lactate dehydrogenase and Group C) examines the addition of rituximab to the standard FAB LMB 96 (COG-C5961) chemotherapy regimen. Additionally, the dose-adjusted EPOCH-R regimen (etoposide, prednisone, vincristine, doxorubicin, and rituximab) will be tested in a single-arm, phase II trial for pediatric patients with primary mediastinal B-cell lymphoma.

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