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Non-Hodgkin's Lymphoma

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Treatment for Indolent, Noncontiguous Stage II / III / IV Adult NHL



    Rituximab may be considered as first-line therapy, either alone or in combination with other agents.

    Standard therapy includes rituximab, an anti-CD20 monoclonal antibody, either alone or in combination with purine nucleoside analogs such as fludarabine or 2-chlorodeoxyadenosine, alkylating agents (with or without steroids), or combination chemotherapy.

    Evidence (rituximab):

    • Four randomized, prospective studies of previously untreated patients (involving more than 1,300 patients) and one Cochrane meta-analysis including both untreated and previously treated patients (involving almost 1,000 patients) have compared rituximab plus combination chemotherapy with chemotherapy alone.[30,33,36]; [37,38][Level of evidence: 1iiA]
      • Rituximab plus chemotherapy was superior in terms of event-free survival or progression-free survival (PFS) (ranging from 2–3 years) in all of the studies and in terms of OS in all but one study (absolute benefit ranging from 6%–13% at 4 years, P < .04 and hazard ratio [HR] = 0.63 [0.51–0.79] for the meta-analysis).
      • All of these trials were performed in symptomatic patients who required therapy. These results do not negate watchful waiting when appropriate.

    Purine nucleoside analogs

    • Fludarabine.[1,39,40]
    • 2-chlorodeoxyadenosine.[41,42]

    Alkylating agents (with or without steroids)

    Combination chemotherapy

    • CVP: cyclophosphamide + vincristine + prednisone.[1,44]
    • CVP followed by rituximab maintenance.[45]
    • C-MOPP: cyclophosphamide + vincristine + procarbazine + prednisone.[46,47]
    • CHOP: cyclophosphamide + doxorubicin + vincristine + prednisone.[43,48]
    • FND: fludarabine + mitoxantrone +/- dexamethasone, as evidenced in the SWOG-9501 trial, for example.[49,50]

    Yttrium-90-labeled ibritumomab tiuxetan and iodine-131-labeled tositumomab

    Yttrium-90-labeled ibritumomab tiuxetan and iodine-131-labeled tositumomab are available for previously untreated and relapsing patients with minimal (<25%) or no marrow involvement with lymphoma, as was shown in the SWOG-9911 trial, for example.[51,52] Randomized prospective studies are required to determine the optimal utilization of this modality.[53]


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