title: Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor.
abstract: OBJECTIVE
  The study was undertaken to improve the results of intensive chemotherapy in chronic myelogenous leukemia (CML) in accelerated (CML-AP) and blastic phases (CML-BP) by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) as supportive therapy.
  
  
  METHODS
  Forty-eight patients were treated with daunorubicin 120 mg/m2 intravenously on day 1, cytarabine (ara-C) 1.5 g/m2/d by continuous infusion over 24 hours for 4 days, and Solu-Medrol (methylprednisolone; The Upjohn Co, Kalamazoo, MI) 100 mg/d for 5 days, followed on day 5 by GM-CSF 125 micrograms/m2/d over 6 hours until recovery of granulocyte count above 2.0 x 10(3)/microliters. Twenty-four patients had CML-BP, and 24 had CML-AP.
  
  
  RESULTS
  During remission induction, 45 patients (94%) developed febrile episodes (fever of unknown origin, 23 patients [48%]; documented infections, 22 patients [46%]). The median time to recovery of granulocyte count above 0.5 x 10(3)/microliters was 29 days and to platelet count above 30 x 10(3)/microliters, 28 days. Overall, 14 of 48 patients (29%) achieved a complete hematologic remission (CHR), and seven (15%) reverted to a second chronic phase. CHR was noted in eight of 24 patients with CML-BP (33%), and in six of 24 patients with CML-AP (25%). Cytogenetic responses were observed in 11 patients (23%), but were transient. Sixteen patients developed either fluid retention, hypotension, pleuropericardial effusions, or pericarditis, or a combination of these side effects. These side effects were severe in four patients and are likely to be disease-associated, as a similar regimen of intensive chemotherapy and GM-CSF at the same dose and schedule in acute lymphocytic leukemia was not associated with these side effects.
  
  
  CONCLUSIONS
  The results pertinent to remission rates, induction mortality, myelosuppression profile and related complications, and overall survival were not significantly improved compared with previous experience. In summary, the results of intensive chemotherapy in CML-transformed phases remain poor, despite the addition of GM-CSF as a supportive measure.
authors.affiliation: Department of Hematology, MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
authors.forename: D
authors.initials: D
authors.lastname: Kontoyiannis
authors.forename: J
authors.initials: J
authors.lastname: Gutterman
authors.forename: M J
authors.initials: MJ
authors.lastname: Keating
authors.forename: E H
authors.initials: EH
authors.lastname: Estey
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: M B
authors.initials: MB
authors.lastname: Rios
authors.forename: M
authors.initials: M
authors.lastname: Beran
authors.forename: A
authors.initials: A
authors.lastname: Deisseroth
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001752:Blast Crisis / Q000188:drug therapy*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy*; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003630:Daunorubicin