title: The addition of daunorubicin to imatinib mesylate in combination with cytarabine improves the response rate and the survival of patients with myeloid blast crisis chronic myelogenous leukemia (AFR01 study).
abstract: BACKGROUND
  The median survival of patients with chronic myelogenous leukemia in myeloid blast crisis (MBC-CML) is poor even for patients treated with tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  We conducted a dose-escalating study of daunorubicin combined to fixed doses of IM (imatinib mesylate, 600 mg/d) and cytarabine (200 mg/d for 7 days), followed by hematopoietic stem cell transplantation or maintenance therapy with single-agent IM in patients with MBC-CML at onset or after failure of therapy excluding TKIs.
  
  
  RESULTS
  Thirty-six patients were evaluated. Median follow-up is 6.1 years. Daunorubicin was escaladed up to 45 mg/m(2)/d 3 days. Twenty eight patients (77.7%) had hematologic response including 20 patients (55.5%) in complete hematologic response (CHR). Patients who received daunorubicin at 30-45 mg/m(2)/d had higher CHR rates compared to other patients. Median overall survival was 16 months. Overall survival in patients with hematological response was 35.4 months. Better results were observed in patients diagnosed with MBC-CML at onset.
  
  
  CONCLUSIONS
  The combination of IM with a standard "3+7" regiment was well tolerated and provided a high response rate. More than 55% of the patients achieved CHR and hematopoietic stem cell transplantation (SCT) was feasible in half of the cases. This trial was registered at www.clinicaltrials.gov as # NCT00219765.
authors.affiliation: Hôpital Necker, AP-HP, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Deau
authors.forename: Franck E
authors.initials: FE
authors.lastname: Nicolini
authors.forename: Joelle
authors.initials: J
authors.lastname: Guilhot
authors.forename: Françoise
authors.initials: F
authors.lastname: Huguet
authors.forename: Agnès
authors.initials: A
authors.lastname: Guerci
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.forename: Cécile
authors.initials: C
authors.lastname: Pautas
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
authors.forename: Denis
authors.initials: D
authors.lastname: Guyotat
authors.forename: Pascale
authors.initials: P
authors.lastname: Cony-Makhoul
authors.forename: Martine
authors.initials: M
authors.lastname: Gardembas
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hayette
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Isabelle Radford
authors.initials: IR
authors.lastname: Weiss
authors.forename: Delphine
authors.initials: D
authors.lastname: Réa
authors.forename: Sylvie
authors.initials: S
authors.lastname: Castaigne
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D003630:Daunorubicin