title: Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia.
abstract: BACKGROUND
  In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study.
  
  
  METHODS
  Having reported feasibility previously, we hereby report the efficacy of escalated imatinib (200 mg, 400 mg, 600 mg or 800 mg) in combination with two cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1 to 7) in 162 patients with chronic myeloid leukemia.
  
  
  RESULTS
  With a median follow-up of 55 months, the 5-year cumulative incidences of complete cytogenetic response, major molecular response, and complete molecular response were 89%, 71%, and 53%, respectively. A higher Sokal risk score was inversely associated with complete cytogenetic response (hazard ratio of 0.63; 95% confidence interval, 0.50-0.79, P<0.001). A higher dose of imatinib and a higher dose of cytarabine were associated with increased complete molecular response with hazard ratios of 1.60 (95% confidence interval, 0.96-2.68, P=0.07) and 1.66 (95% confidence interval, 1.02-2.72, P=0.04), respectively. Progression-free survival and overall survival rates at 5 years were 92% and 96%, respectively. Achieving a major molecular response at 1 year was associated with complete absence of progression and a probability of achieving a complete molecular response of 89%.
  
  
  CONCLUSIONS
  The addition of intravenous cytarabine to imatinib as upfront therapy for patients with chronic myeloid leukemia is associated with a high rate of complete molecular responses (Clinicaltrials.Gov Identifier: NCT00028847).
authors.affiliation: Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Deenik
authors.forename: Jeroen J W M
authors.initials: JJ
authors.lastname: Janssen
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Gregor E G
authors.initials: GE
authors.lastname: Verhoef
authors.forename: Willem M
authors.initials: WM
authors.lastname: Smit
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Kersten
authors.forename: Simon M G J
authors.initials: SM
authors.lastname: Daenen
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Augustin
authors.initials: A
authors.lastname: Ferrant
authors.forename: Anton V M B
authors.initials: AV
authors.lastname: Schattenberg
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Marinus
authors.initials: M
authors.lastname: van Marwijk Kooy
authors.forename: Shulamit
authors.initials: S
authors.lastname: Wittebol
authors.forename: Roelof
authors.initials: R
authors.lastname: Willemze
authors.forename: Pierre W
authors.initials: PW
authors.lastname: Wijermans
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Valk
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D003561:Cytarabine / Q000008:administration & dosage*; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate