2-Chlorodeoxyadenosine in the Treatment of Hairy Cell Leukemia and Chronic Lymphocytic Leukemia

Abstract

More than 450 patients with hairy cell leukemia have been treated at the Scripps Clinic. Of 144 patients followed for a median of 14.2 months (range, 8.1–70 months), 123 (85%) obtained complete responses, 17 (12%) partial responses, 3 (2%) did not respond, and 1 patient was unevaluable. So far, 4 patients have relapsed at a median of 36 months (range, 12–48 months). Fever was the principal toxicity occurring in 43% of patients. Five patients resistant (3 patients) or intolerant (2 patients) to deoxycoformycin were also treated. Of these 5 patients, 4 obtained complete responses, including 2 patients resistant to deoxycoformycin, and 1 patient a partial response, suggesting a possible lack of cross-resistance between deoxycoformycin and 2–CdA in hairy cell leukemia. Other single-institution studies have documented similar response rates and toxicities.

Ninety patients with advanced chronic lymphocytic leukemia were treated with 2–CdA administered either as a 0.1 mg/kg/day 7–day continuous intravenous infusion or as a 0.028–0.14 mg/kg/day 2–hour bolus for 5 consecutive days. Four patients (4%) obtained complete responses and 36 patients (40%) partial responses, using NCI-sponsored Working Group guidelines. Of the 50 patients who were non-responders, 27 (54%) had a ≥ 50% sustained reduction in the absolute lymphocyte count. The ratio of deoxycytidine kinase to cytoplasmic 5′-nucleotidase was predictive of 2–CdA responsiveness. Fourteen patients with fludarabine-failed chronic lymphocytic leukemia were also treated. No responses were achieved and 2 patients had progressive disease. Six patients had a ≥ 50% reduction in the absolute lymphocyte count. The efficacy and safety of 2–CdA in fludarabine-failed chronic lymphocytic leukemia patients remains to be evaluated in larger numbers of patients.

Key Words:

• 2–chlorodeoxyadenosine
• hairy cell leukemia
• chronic lymphocytic leukemia