A Randomized Study of Daily Versus Weekly Administration of 2-Chlorodeoxyadenosine in Patients with Hairy Cell Leukemia.

Background: In hairy cell leukemia (HCL), one cycle of 2-chlorodeoxyadenosine (CDA) is considered a standard treatment. The treatment often results in a high frequency of severe neutropenia and neutropenic fever. Weekly administration of CDA has been reported as effective as daily administration, but with a reduction of febrile episodes and infectious complications. This trial compares the two regimens for efficacy and toxicity.

Design and Methods: HCL patients (pts) were randomized to receive either the standard schedule CDA 0.14 mg/kg/day as a s.c. bolus injection on days 1–5 (Arm A) or the experimental schedule of one weekly dose of CDA 0.14 kg/day as a s.c. bolus injection on five consecutive weeks (Arm B). The primary endpoint was the average of 6 weekly white blood cell count after randomization, analyzed using ANCONA to adjust for baseline count. 100 pts were required to detect a difference between 0.8 G/L and 1.2 G/L with 5% type I errror and 80% power. Secondary endpoints were response rates, other acute hematotoxicity, acute infection rate and fever within 10 weeks, remission duration (RD), event-free survival (EFS) and overall survival. Clinical and laboratory examinations were repeated weekly during the first 6 weeks, then biweekly up to week 10, every 3 months up to 2 years and every 6 months thereafter. Response was assessed at week 10, then every 6 months up to 2 years, and every year thereafter.

Results: 50 pts were enrolled to each arm. There was no significant difference between treatment arms (A vs. B) in the primary endpoint (2.2 G/L vs. 3.0 G/L), the rate of grade 3/4 leucocytopenia (94% vs. 84%) or neutropenia (90% vs. 80%), acute infection of any grade (44% vs. 40%), fever (44% vs. 38%), hospitalization (38% vs. 34%), and blood transfusion (22% vs. 30%). Response rate (CR + PR) at week 10 was 78% with 95% confidence interval (CI) (64%, 88%) vs. 68% with CI (54%, 80%) (1-sided p-value 0.13). Over all follow-up visits the best response rate was improved to 86% in both arms. The median follow-up time was 50.2 months vs. 42.3 months. The median values for RD and EFS have not been reached, and the between-arm differences were not significant. One pt in each arm died during treatment and one additional pt in arm A died during follow-up.

Conclusions: Weekly application of CDA fails to show any advantage in toxicity or efficacy compared to standard approach.