Combination of Cytosine-Arabinoside (ARA-C), Cyclophosphamide and Prednisone in the Treatment of B-Chronic Lymphocytic Leukemia in Advanced Stages and Progressive Disease

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Abstract
Recently the major advances in B-chronic lymphocytic leukemia (B-CLL) have been in defining biological characteristics and prognostic criteria. However it remains to be established which is the best therapeutic approach following the first line treatment, particularly when the patients are completely unresponsive to the standard treatment using Chlorambucil (CHL) and Prednisone (PDN) and the disease is progressive. We report the results of a combination regimen using Cytosine-Arabinoside (ARA-C), Cyclophosphamide (CTX) and PDN in 19 B-CLL patients with advanced disease, resistant to CHL + PDN. The treatment schedules were as follows: Schedule A) ARA-C 60mg/sqm from day 1 to 4 s.c., CTX 75 mg/sqm from day 1 to 4 i.v., PDN 40 mg/sqm from day 1 to 4 p.o.: courses were repeated every 4 weeks for 6 months; Schedule B) ARA-C 100 mg/sqm from day 1 to 7 s.c., CTX 100 mg/sqm from day 8 to 14 i.v., PDN 40 mg/sqm from day 1 to 21 p.o.: courses were repeated every 4 weeks for 6 months. Fourteen pts were treated with schedule A and 5 pts with schedule B. We observed 9 partial remissions (PR), 5 cases with no response and 5 patients with progression. The median duration of PR is 20 months and two patients remain in PR after 18 and 60 months, respectively. The combination of ARA-C, CTX plus PDN is highly effective in advanced stages and in pretreated B-CLL but we need larger randomized studies to draw more definitive conclusions.