A multicenter, open, non‐comparative, phase II study of the combination of cladribine (2‐chlorodeoxyadenosine), cytarabine, and G‐CSF as induction therapy in refractory acute myeloid leukemia – a report of the Polish Adult Leukemia Group (PALG)

Abstract: Objectives: To evaluate the efficacy and toxicity of cladribine (2‐chlorodeoxyadenosine, 2‐CdA), cytarabine (Ara‐C), and granulocyte‐colony stimulating factor (G‐CSF) (CLAG) regimen in refractory acute myeloid leukemia (AML) in the multicenter phase II study. Methods: The induction chemotherapy consisted of 2‐CdA 5 mg/m 2 , Ara‐C2 g/m 2 , and G‐CSF. In the case of partial remission (PR), a second CLAG was administered. Patients in complete remission (CR) received two consolidation courses based on HD Ara‐C, mitoxantrone or idarubicine, with or without 2‐CdA. Results: Fifty‐eight patients from 11 centers were registered; 50 primary resistant and eight early relapsed (CR1 < 6 months). CR was achieved in 29 (50%) patients, 19 (33%) were refractory, and 10 (17%) died early. Forty of 50 primary resistant patients received daunorubicin (DNR) and Ara‐C as the first‐line induction therapy (DA‐7), 10 received additional 2‐CdA (DAC‐7). The CR rates after CLAG were 58% and 10%, respectively in each group ( P = 0.015). Five of six patients with myelodysplastic syndrome (MDS)/AML achieved CR. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS, 1 yr) for the 58 patients as a whole, and the 29 patients in CR were 42% and 65%, respectively. Disease‐free survival (DFS, 1 yr) was 29%. Only first‐line induction treatment with DA‐7 significantly influenced the probability of CR after CLAG. None of the analyzed factors significantly influenced DFS and OS. Conclusion: CLAG regimen has significant anti‐leukemic activity and an acceptable toxicity in refractory AML. The addition of 2‐CdA to the first‐line induction treatment may worsen the results of salvage with CLAG. The high CR rate in patients with MDS preceding AML deserves further observation.