title: 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: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, Medical University, Łodź, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Wrzesień-Kuś
authors.forename: T
authors.initials: T
authors.lastname: Robak
authors.forename: E
authors.initials: E
authors.lastname: Lech-Marańda
authors.forename: A
authors.initials: A
authors.lastname: Wierzbowska
authors.forename: A
authors.initials: A
authors.lastname: Dmoszyńska
authors.forename: M
authors.initials: M
authors.lastname: Kowal
authors.forename: J
authors.initials: J
authors.lastname: Hołowiecki
authors.forename: S
authors.initials: S
authors.lastname: Kyrcz-Krzemień
authors.forename: S
authors.initials: S
authors.lastname: Grosicki
authors.forename: S
authors.initials: S
authors.lastname: Maj
authors.forename: A
authors.initials: A
authors.lastname: Hellmann
authors.forename: A
authors.initials: A
authors.lastname: Skotnicki
authors.forename: W
authors.initials: W
authors.lastname: Jedrzejczak
authors.forename: K
authors.initials: K
authors.lastname: Kuliczkowski
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017338:Cladribine / Q000008:administration & dosage* / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009190:Myelodysplastic Syndromes / Q000150:complications; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D017338:Cladribine