What is the role of medication in the treatment of cold agglutinin disease?

Updated: Aug 28, 2018
  • Author: Salman Abdullah Aljubran, MD; Chief Editor: Michael A Kaliner, MD  more...
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Folic acid supplementation is advisable in individuals with cold agglutinin disease to meet the increased requirements for red blood cell production, due to hemolytic anemia.

Immunosuppressive and immunomodulating drugs are seldom necessary; however, in cases with underlying malignancies, these agents are required to treat the malignancy. Potent immunosuppression to reduce the production of monoclonal antibody and to reduce/eliminate the abnormal lymphocyte clone has been achieved with cyclophosphamide (1200 mg) and vincristine (2 mg) administered intravenously (IV) on day 1 and prednisone (80 mg/d) administered orally for 5 days, with some beneficial effect in an anecdotal case. [16]

The same patient was treated 10 months later with IV fludarabine (25 mg/m2) daily for 5 days and then every 28 days for 3 courses. Following a third course of treatment, the patient went into remission that lasted for at least 4 years. [16]

Corticosteroids alone may not be routinely useful in patients with cold agglutinin disease, although occasionally a patient may have a clinical response. Patients with mixed cold and warm immune hemolytic anemia are more likely to have a response because of the warm antibody component.

The corticosteroid-sparing agent chlorambucil has also been used to treat cold agglutinin disease. [63]

Rituximab and fludarabine

Rituximab has been widely recognized as being very effective for treating cold agglutinin disease. One study documented a high response rate and durable remissions following therapy using a combination of fludarabine and rituximab. While the results from this study appear positive, extreme caution should be exercised, because the immunosuppressive effects of rituximab superimpose on those of fludarabine. [54]

Bear in mind that one uncommon reported adverse effect of fludarabine is the appearance of a warm autoantibody–induced autoimmune hemolytic anemia. However, in the authors' experience, patients with Coombs-positive hemolytic anemias have been treated effectively with fludarabine. Responses to interferon alfa therapy have been reported. This therapy may be useful for some B-cell neoplasms. [64]

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