Level of Evidence = B
First-line treatment of CLL patients with purine antagonists appears to be more effective than alkylator-based therapy in terms of obtaining a complete response and a longer progression-free survival, but purine antagonist use is associated with more severe infections and autoimmune hemolytic anemia.
A Cochrane review  included 5 studies with a total of 1838 subjects. Purine antagonists (four trials used fludarabine and one trial cladribine) were compared to alkylator-based therapy (chlorambucil alone or with prednisone three studies, or cyclophosphamide in combination CAP two studies or CHOP one study). In the purine antagonist group the relative risk for achieving an overall response (RR 1.22, 95% CI 1.13 to 1.31, 5 trials, n=1751,) and complete remission (RR 1.94, 95% CI 1.65 to 2.28) was significantly higher than in alkylator group, resulting in a longer progression-free survival (HR for death 0.70, 95% CI 0.61 to 0.82, 4 trials, n=1638). Purine antagonists did not statistically significantly improve overall survival after treatment (HR for death 0.89, 95% CI 0.78 to 1.01, 4 trials, n=1638). The incidence of severe infections was higher in patients receiving treatment with purine antagonists (RR 1.83, 95% Cl 1.30 to 2.58, 4 trials, n=1620), but therapy-related mortality did not differ significantly (RR 0.94, 95% Cl 0.45 to 1.95). Overall incidence of hemolytic anemia was low, but increased in the purine antagonist group (RR 3.36, 95% CI 1.27 to 8.91, 3 trials, n=1258). Comment: The level of evidence is downgraded because of inconsistent data. None of the studies included quality of life data.
1. Steurer M, Pall G, Richards S, Schwarzer G, Bohlius J, Greil R. Purine antagonists for chronic lymphocytic leukaemia. Cochrane Database Syst Rev 2006 Jul 19;3:CD004270. [PMID:16856041]
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