title: Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study.
abstract: OBJECTIVE
  The goal of this study was to evaluate whether the addition of a purine analog, cladribine or fludarabine, to the standard induction regimen affects the outcome of adult patients with acute myeloid leukemia (AML).
  
  
  METHODS
  A cohort of 652 untreated AML patients with median age 47 years (range, 17 to 60 years) were randomly assigned to receive one of three induction regimens: DA (daunorubicin plus cytarabine), DAC (DA plus cladribine), or DAF (DA plus fludarabine). Postremission treatment was the same for all arms.
  
  
  RESULTS
  Complete remission rate in the DAC arm was higher compared with the DA arm (67.5% v 56%; P = .01) as a consequence of reduced incidence of resistant disease (21% v 34%; P = .004). There was no significant difference in early outcome between the DAF and DA arms. The probability of overall survival was improved for the DAC arm (45% ± 4% at 3 years) compared with the DA arm (33% ± 4%; P = .02), and leukemia-free survival was comparable. Long-term outcome did not differ significantly for the comparison of the DAF and DA arms. A survival advantage of the DAC arm over the DA arm was observed among patients age 50 years or older (P = .005), those with initial leukocyte count above 50 × 10(9)/L (P = .03), and those with unfavorable karyotype (P = .03). DAF revealed a significant advantage over DA in patients with adverse karyotype (P = .02).
  
  
  CONCLUSIONS
  The addition of cladribine to the standard induction regimen is associated with increased rate of complete remission and improved survival of adult patients with AML.
authors.affiliation: Comprehensive Cancer Center M. Curie-Sklodowska Memorial Institute, Branch Gliwice, Gliwice, Poland. jholowiecki@io.gliwice.pl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grosicki
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Slawomira
authors.initials: S
authors.lastname: Kyrcz-Krzemien
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
authors.forename: Aleksander B
authors.initials: AB
authors.lastname: Skotnicki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Sulek
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.forename: Wieslaw W
authors.initials: WW
authors.lastname: Jedrzejczak
authors.forename: Barbara
authors.initials: B
authors.lastname: Zdziarska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Krystyna
authors.initials: K
authors.lastname: Zawilska
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Komarnicki
authors.forename: Marek
authors.initials: M
authors.lastname: Kielbinski
authors.forename: Beata
authors.initials: B
authors.lastname: Piatkowska-Jakubas
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wierzbowska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wach
authors.forename: Olga
authors.initials: O
authors.lastname: Haus
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017338:Cladribine / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016019:Survival Analysis; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D003561:Cytarabine; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine; D003630:Daunorubicin