title: A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group.
abstract: Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs). Synergistic interaction between FAMP or 2-CdA with cytarabine (cytosine arabinoside, Ara-C) has been demonstrated in preclinical and clinical studies. The current multicenter phase II study was initiated to evaluate the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2), mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (CLAG-M) in refractory AML. In case of partial remission, a second CLAG-M was administered. Patients in complete remission (CR) received consolidation courses based on high-dose Ara-C and MIT with or without 2-CdA. Forty-three patients from five centers were registered: 25 primary resistant and 18 relapsed. CR was achieved in 21 (49%) patients, 20 (47%) were refractory and 2 (5%) died early. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS; 1 year) for the 42 patients as a whole and the 20 patients in CR were 43% and 73%, respectively. Disease-free survival (1 year) was 68.6%. None of the analyzed prognostic factors influenced the CR and OS probability significantly. We conclude that CLAG-M regimen has significant antileukemia activity in refractory AML, which seems to be better than the activity of many other regimens. The toxicity of the treatment is acceptable.
authors.affiliation: Department of Hematology, Medical University of Lódz, ul. Pabianicka 62, 93-513, Lódz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Wrzesień-Kuś
authors.forename: T
authors.initials: T
authors.lastname: Robak
authors.forename: A
authors.initials: A
authors.lastname: Wierzbowska
authors.forename: E
authors.initials: E
authors.lastname: Lech-Marańda
authors.forename: A
authors.initials: A
authors.lastname: Pluta
authors.forename: E
authors.initials: E
authors.lastname: Wawrzyniak
authors.forename: A
authors.initials: A
authors.lastname: Krawczyńska
authors.forename: K
authors.initials: K
authors.lastname: Kuliczkowski
authors.forename: G
authors.initials: G
authors.lastname: Mazur
authors.forename: M
authors.initials: M
authors.lastname: Kiebiński
authors.forename: A
authors.initials: A
authors.lastname: Dmoszyńska
authors.forename: M
authors.initials: M
authors.lastname: Wach
authors.forename: A
authors.initials: A
authors.lastname: Hellmann
authors.forename: W
authors.initials: W
authors.lastname: Baran
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
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D017338:Cladribine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000139:chemically induced; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D017338:Cladribine; D008942:Mitoxantrone