title: [Treating patients with acute myeloid leukemias (AML) according to the protocol of the AML-01.10 Russian multicenter randomized trial: the coordinating center's results].
abstract: OBJECTIVE
  To make a randomized comparison of 2 consolidation treatment options (two patient groups): 2 cycles of cytarabine in average (Ig/m2 in Group 2) and standard (100 mg/mi2 in Group 1) doses in combination with idarubicin (8-12 mg/m2) and mitoxantrone (10 mg/m2), after two 7+3 induction cycles of daunorubicin (60 mg/mi2) and subsequent 6 cycles of maintenance therapy.
  
  
  METHODS
  In January 2010 to October 2013, a Russian multicenter trial was conducted to treat patients with acute myeloid leukemias (AML) in accordance with the AML-01.10 protocol (ClinicalTrials.gov Identifier: NCT01587430). The trial enrolled 243 AML patients from 21 centers, including 71 patients (median age 38 years) from the State Hematology Center, Ministry of Health of the Russian Federation; 35 and 36 patients were randomized to Groups 1 and 2, respectively. The randomized groups were balanced by basic clinical and laboratory parameters. Favorable, intermediate, and high cytogenetic prognoses were in 14 (21.9%), 40 (62.5%), and 10 (15.6%) patients, respectively.
  
  
  RESULTS
  Prior to treatment, 2 patients died; one patient refused treatment. Fifty-eight (85.3%) of the 68 patients achieved complete remission (CR); early deaths was in 2 (2.9%) and resistance in 8 (11.8%). Four (6.9%) patients died during CR. Protocol deviations (doses, intervals, and the number of cycles) were recorded in 12 (20.7%) of the 58 patients. Other 8 (11.8%) patients were switched to low-dose cytarabine because of complications, withdrawn from the protocol and not included into the analysis of randomized comparison. Twenty allogeneic bone marrow transplantations (allo-BMT) (7 related, 12 unrelated, and 1 haploidentical) were performed; of them 15 allo-BMTs were done during first CR. In the 68 patients, 3-year overall survival (OS) was 45.6%; relapse-free survival (RFS) was 41.5%. OS was 64.6% in Group 1 and 58.3% in Group 2; RFS was 62 and 38.8% in Groups 1 and 2, respectively (p>0.5). In the favorable, intermediate, and high prognosis groups, OS was 79.5, 60, and 31.1% and RFS was 81.8, 41.3, and 33.3%, respectively (p=0.1). The consolidation treatment option unchanged survival rates in the above risk groups. Unachieved CR after the first cycle considerably decreased RFS (33.9% versus 60%) and served as an indication for allo-BMT during first CP (RFS without BMT was 0; that with BMT was 78%).
  
  
  CONCLUSIONS
  No differences were found between both consolidation options according to long-term results. Protocol deviations were recorded in one-third of the patients. While implementing the protocol, the efficiency of treatment was high. Allo-BMT during first CR substantially increased RFS if CP was not achieved after the first cycle.
authors.forename: E N
authors.initials: EN
authors.lastname: Parovichnikova
authors.forename: V V
authors.initials: VV
authors.lastname: Troitskaia
authors.forename: G A
authors.initials: GA
authors.lastname: Kliasova
authors.forename: L A
authors.initials: LA
authors.lastname: Kuz'mina
authors.forename: A N
authors.initials: AN
authors.lastname: Sokolov
authors.forename: E V
authors.initials: EV
authors.lastname: Paramonova
authors.forename: G M
authors.initials: GM
authors.lastname: Galstian
authors.forename: S A
authors.initials: SA
authors.lastname: Kessel'man
authors.forename: M Iu
authors.initials: MIu
authors.lastname: Drokov
authors.forename: V A
authors.initials: VA
authors.lastname: Vasil'eva
authors.forename: T N
authors.initials: TN
authors.lastname: Obukhova
authors.forename: S M
authors.initials: SM
authors.lastname: Kulikov
authors.forename: V G
authors.initials: VG
authors.lastname: Savchenko
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060830:Consolidation Chemotherapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012426:Russia
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone; D015255:Idarubicin; D003630:Daunorubicin