Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia.

The aim of the study was efficacy and toxicity evaluation of combination of 2-Chlorodeoxyadenosine (2-CdA) with cytarabine (Ara-C) and G-CSF (CLAG regimen) as reinduction therapy in patients with refractory or relapsed acute myeloid leukemia (AML). The protocol stipulated an infusion of 5 mg/m2 of 2-CdA over 2 hours daily for 5 consecutive days. A 4-hour infusion of Ara-C (2 g/m2) was started 2 hours after each infusion of 2-CdA. G-CSF at a dose 300 microg s.c was given 24 hours before the first dose of 2-CdA for 6 days. In case of WBC>20x10(9)/l G-CSF was started simultaneously with 2-CdA. In the case of complete response (CR) consolidation treatment with 2-CdA containing regimens was started. In case of partial response a second identical course of CLAG was given. Response criteria were established according to those developed by the NCI Sponsored Workshop. Among 20 patients accrued all but 2 received at least one course of CLAG induction therapy in the planned doses. 10/20 (50%) (95% CI 27-73%) patients achieved a CR with a median duration of 22.5 weeks (range 3.5-53 weeks). Two (10%) patients had a PR and 8 were non-responders. One patient underwent peripheral blood stem cell transplantation. Overall 4 patients are in continuous CR with a median duration of 16.2 weeks (range 3.5-36.5). Among non-responders two patients did not receive the full dose of treatment because of complications during the cycle, both of them died; 3 died early after complete induction therapy before recovery of the bone marrow and 3 were resistant to CLAG. All 20 patients but one experienced granulocytopenia <0.2x10(9)/l and thrombocytopenia <20x10(9)/l. Median time to reach PMN>0.5x10(9) G/l was 18.7 days and platelets>50x10(9)/l was 27.2 days. In conclusion, the CLAG regimen had significant antileukemic activity and acceptable toxicity as reinduction treatment in refractory or relapsed AML patients.