Cladribine in Weekly Versus Daily Schedule for Untreated Active Hairy Cell Leukemia: Final Report of Polish Adult Leukemia Group (PALG) Prospective, Randomized, Multicenter Trial.

Cladribine (2-chlorodeoxyadenosine, 2-CdA) has dramatically improved prognosis of hairy cell leukemia (HCL), though the 2-CdA treatment-associated life-threatening infections may shorten potentially long-term survival of HCL patients. In search of optimal mode of 2-CdA administration in HCL, we compared the standard 5-day 2-CdA protocol with a novel weekly 2-CdA schedule that was suggested to be equally effective, but less toxic. Between the 1^st January 1998 and the 31^st September 2005, 132 patients with previously untreated, active HCL from 14 hematology centers were included to the study. Patients were randomly assigned to receive 2-CdA at 0.12 mg/kg in 2-hour intravenous infusion for 5 days (64 patients), or 2-CdA at 0.12 mg/kg in 2-hour intravenous infusion once a week for 6 weeks (62 patients). The response to chemotherapy was evaluated according to the NCI guidelines and treatment-related toxicity was recorded using standard WHO criteria. One hundred and sixteen patients were included in the final analysis of the trial. Comparison of the treatment response between daily and weekly 2-CdA protocols showed similar complete remission rate (76% and 72%, p=0.86) as well as similar overall response rate (95% and 91%, p=0.41). Survival analysis did not show significant difference between the study arms. Median progression-free survival equaled 4.3 years (95%CI = 3.3 – 5.2) and 5.1 years (95%CI = 4.7 – 5.6) (p=0.28) for patients treated with daily and weekly schedule, respectively. The estimated 6.5 year overall survival was 91% for daily and 88% for weekly 2-CdA protocol, p = 0.40. Interestingly, the analysis of adverse events did not confirm lower toxicity of the weekly 2-CdA schedule. Of special interest, there were no significant differences between daily and weekly protocol in the rate of treatment-related neutropenia (47% vs. 47%, p=0.97), the rate of grade 3/4 infections (18% vs. 26%, p=0.28), or the rate of 2-CdA-related septic deaths (2% vs. 1%, p=0.64). In conclusion, the results of our randomized study indicate that HCL treatment based on weekly 2-CdA infusions for 6 weeks is equally effective, but not safer than standard 5-day 2-CdA protocol.