High-Dose Cytosine Arabinoside in Chronic Lymphocytic Leukemia: A Clinical and Pharmacologic Analysis

Abstract

Twenty-seven patients with B-cell chronic lymphocytic leukemia (CLL) or a related lymphoid malignancy were treated with high-dose cytosine arabinoside (ara-C) at a dosage of 3 gm/m² administered over 2 hours every 12 hours at one to four doses per course, which were repeated at 4-week intervals. Median patient age was 60 years. Fifty-four percent of CLL patients had Rai stage III or IV disease and the median number of prior therapies was three. Two patients achieved a complete response, five had a partial response, and two had clinical improvement for an overall response rate of 33%. The median duration of response was 9 months. Myelosuppression and infection were the main toxicities. Intracellular levels of the active metabolite ara-C triphosphate varied among patients, but comparisons of pharmacokinetic parameters revealed no significant differences between responders and non-responders. We conclude that high-dose ara-C has modest activity in CLL and that its use in combination with other agents in the treatment of CLL is warranted.

Key Words:

• CLL
• cytosine arabinoside