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)

Eur J Haematol. 2003 Sep;71(3):155-62. doi: 10.1034/j.1600-0609.2003.00122.x.


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/m2, Ara-C2 g/m2, 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cladribine / administration & dosage*
  • Cladribine / adverse effects
  • Cytarabine / administration & dosage*
  • Cytarabine / adverse effects
  • Disease-Free Survival
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Myelodysplastic Syndromes / complications
  • Prognosis
  • Recurrence
  • Remission Induction
  • Survival Rate


  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Cladribine

Supplementary concepts

  • CLAG protocol