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Non-Hodgkin's Lymphoma

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Indolent NHL

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    Asymptomatic patients can be monitored for evidence of disease progression without immediate need for chemotherapy.[10,27,28]

    Prognostic factors associated with symptoms requiring therapy include the following:

    • Age 70 or older.
    • Beta-2-microglobulin of 3 mg/dL or more.
    • Increased serum LDH.[27]

    Therapeutic approaches

    The management of lymphoplasmacytic lymphoma is similar to that of other low-grade lymphomas, especially diffuse small lymphocytic lymphoma/chronic lymphocytic leukemia.[25,26,27,29,30,31] If the viscosity relative to water is greater than four, the patient may have manifestations of hyperviscosity. Plasmapheresis is useful for temporary, acute symptoms (such as retinopathy, congestive heart failure, and central nervous system [CNS] dysfunction) but should be combined with chemotherapy for prolonged control of the disease. Symptomatic patients with a serum viscosity of not more than four are usually started directly on chemotherapy. Therapy may be required to correct hemolytic anemia in patients with chronic cold agglutinin disease; rituximab, cyclophosphamide, and steroids are often employed.[28] Occasionally, a heated room is required for patients whose cold agglutinins become activated by even minor chilling.

    First-line regimens include rituximab, the nucleoside analogs, and alkylating agents, either as single agents or as part of combination chemotherapy.[32,33,34] Rituximab shows 60% to 80% response rates in previously untreated patients, but close monitoring of the serum IgM is required because of a sudden rise in this paraprotein at the start of therapy.[32,35,36][Level of evidence: 3iiiDiv] The rise of IgM after rituximab can be avoided with the concomitant use of an alkylating agent such as cyclophosphamide or the proteosome inhibitor bortezomib.[28,37] The nucleoside analogs 2-chlorodeoxyadenosine and fludarabine have shown similar response rates for previously untreated patients with lymphoplasmacytic lymphoma.[38,39][Level of evidence: 3iiiDiv] Single-agent alkylators, bortezomib, and combination chemotherapy with or without rituximab also show similar response rates.[37,40,41,42][Level of evidence: 3iiiDiv] Currently, no randomized trials guide clinicians about the initial choice of rituximab, nucleoside analogs, alkylating agents, combination chemotherapy, or combinations of these options.[25,26,32] A combination of bortezomib, dexamethasone, and rituximab has been proposed for its high response rate, rapidity of action, and avoidance of an IgM rebound.[43]

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