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Rituximab/Cyclophosphamide/Dexamethasone Combination Highly Effective in Autoimmune Hemolytic Anemia Associated With Chronic Lymphocytic Leukemia

Rituximab/Cyclophosphamide/Dexamethasone Combination Highly Effective in Autoimmune Hemolytic Anemia Associated With Chronic Lymphocytic Leukemia

The exact mechanism of development of autoimmune hemolytic anemia (AIHA) in chronic lymphocytic leukemia (CLL) is unclear, but the imbalance among lymphocyte subsets is considered to be the basis for the emergence of an autoimmune clone. Treatment of this complication is aimed at immunosuppression with glucocorticosteroids as first-line treatment. Once steroid therapy fails there is no known effective treatment, although various agents are commonly used with variable response rates. We present our results with a combination of drugs targeting the B lymphocytes, in addition to other lymphocyte populations.

Eight CLL patients with Coombs-positive AIHA, who had failed steroid therapy, were treated between December 1998 and March 2000. The treatment regimen consisted of rituximab (Rituxan) given at a dose of 375 mg/m2 IV infusion on day 1, cyclophosphamide (Cytoxan, Neosar) at a dose of 750 to 1,000 mg/m2 IV on day 2, and dexamethasone at 12 mg/d IV on days 1 and 2 and orally from days 3 to 7. This treatment was repeated monthly for 4 months, or it was stopped sooner if a maximally achievable beneficial response was reached. The table below provides the pre- and posttreatment absolute lymphocyte count (ALC) × 1,000/µL, hemoglobin (Hb) in g/dL, and platelets × 1,000/µL:

In five patients the Coombs test became negative after treatment. All patients had a dramatic response, with all but one patient achieving normal Hb levels. The median duration of response in AIHA is in excess of 12 months, and only one patient had a relapse (at 11 months). In addition to AIHA, all patients showed a marked improvement in their underlying CLL. Apart from the first-infusion-related transient reactions with rituximab, there were no undue toxicities.

CONCLUSION: These results demonstrate that our rituximab-based regimen is extremely effective, not only for controlling AIHA, but also the underlying CLL.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

 
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