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Previous Volume 330:319-322 February 3, 1994 Number 5 Next

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ABSTRACT

Background Fludarabine and 2-chlorodeoxyadenosine are nucleoside analogues that have proved effective in patients with chronic lymphocytic leukemia (CLL). Although their mechanism of action is thought to be similar, a small number of patients who do not respond to fludarabine do respond to 2-chlorodeoxyadenosine. The extent to which 2-chlorodeoxyadenosine is effective in patients who do not respond to fludarabine is not known, however.

Methods We treated 28 patients with CLL refractory to fludarabine therapy with a continuous infusion of 2-chlorodeoxyadenosine at a daily dose of 4 mg per square meter of body-surface area for seven days. The treatment could be repeated monthly. The number of treatments ranged from one to five; patients who responded continued to receive treatment until the maximal response was achieved.

Results Two patients (7 percent) had partial remissions, but no patients had complete remissions. One other patient had a substantial response but had residual thrombocytopenia. The rate of response in most affected organs was 20 percent, but anemia or thrombocytopenia rarely improved. Myelosuppression was frequent, and 65 percent of the courses of 2-chlorodeoxyadenosine therapy were accompanied by febrile episodes or infections. Ten patients died within 60 days of starting therapy with 2-chlorodeoxyadenosine; eight deaths were related to infection. The median platelet count at the start of 2-chlorodeoxyadenosine therapy in these 10 patients was 24,000 per cubic millimeter, as compared with 109,000 per cubic millimeter in the other 18 patients. Five patients were alive after a median follow-up of 24 months.

Conclusions Patients with advanced CLL refractory to fludarabine therapy are unlikely to benefit from treatment with 2-chlorodeoxyadenosine. Although 20 percent of the patients have some response, thrombocytopenia and anemia are rarely corrected and may be made worse by 2-chlorodeoxyadenosine therapy.

Source Information

From the Department of Hematology, Box 61, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, where reprint requests should be addressed to Dr. O'Brien.

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2-Chlorodeoxyadenosine Therapy in Chronic Lymphocytic Leukemia
Juliusson G., Liliemark J., Saven A., Piro L., O'Brien S.
Extract | Full Text  
N Engl J Med 1994; 330:1828-1830, Jun 23, 1994. Correspondence

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