JOURNAL ARTICLE
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Beneficial effect of rituximab in combination with oral cyclophosphamide in primary chronic cold agglutinin disease.

Cold agglutinin disease (CAD) is an uncommon autoimmune hemolytic anemia characterized by B-cell proliferation. Conventional therapies for primary CAD such as corticosteroids, oral alkylating agents, splenectomy, interferon alpha, and plasma exchange are often ineffective at controlling the disease. The anti-CD20 monoclonal antibody rituximab (MabThera) depletes B-lymphocytes and thereby interferes with the production of cold agglutinin. We describe an elderly patient with primary (idiopathic) chronic CAD refractory to steroids who was successfully treated with 4 weekly infusions (375 mg/m2) of rituximab and 6 months of oral cyclophosphamide at a dosage of 60 mg/m2 per day. The increase in hemoglobin level and the decline in the plasma cold agglutinin titer were rapid (from the second rituximab infusion). The hematologic remission persisted for at least 8 months after treatment start, with no adverse effects. Rituximab and cyclophosphamide may be supplementary therapeutic modalities whose combination warrants further clinical investigation.

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