title: Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group.
abstract: OBJECTIVE
  Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2-CdA) increase cytotoxic effect of Ara-C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients.
  
  
  METHODS
  The induction chemotherapy consisted of 2-CdA 5 mg/m2, Ara-C 2 g/m2, MIT 10 mg/m2, and granulocyte-colony stimulating factor. In the case of PR, a second CLAG-M was administered. Patients in CR received consolidation courses based on high doses of Ara-C and MIT with or without 2-CdA.
  
  
  RESULTS
  One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty-six patients (58%) achieved CR after one or two courses of CLAG-M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4-23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11-49%). Poor karyotype was the only factor associated with decreased probability of DFS.
  
  
  CONCLUSIONS
  We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.
authors: Department of Hematology, Medical University, Lodz, Poland.
authors: Agnieszka
authors: A
authors: Wierzbowska
authors: Tadeusz
authors: T
authors: Robak
authors: Agnieszka
authors: A
authors: Pluta
authors: Ewa
authors: E
authors: Wawrzyniak
authors: Barbara
authors: B
authors: Cebula
authors: Jerzy
authors: J
authors: Hołowiecki
authors: Sławomira
authors: S
authors: Kyrcz-Krzemień
authors: Sebastian
authors: S
authors: Grosicki
authors: Sebastian
authors: S
authors: Giebel
authors: Aleksander B
authors: AB
authors: Skotnicki
authors: Beata
authors: B
authors: Piatkowska-Jakubas
authors: Kazimierz
authors: K
authors: Kuliczkowski
authors: Marek
authors: M
authors: Kiełbiński
authors: Krystyna
authors: K
authors: Zawilska
authors: Janusz
authors: J
authors: Kłoczko
authors: Agata
authors: A
authors: Wrzesień-Kuś
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D015999:Multivariate Analysis; D016017:Odds Ratio; D011044:Poland; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D017338:Cladribine; D008942:Mitoxantrone