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)

Leuk Res. 2011 Jun;35(6):777-82. doi: 10.1016/j.leukres.2010.11.004. Epub 2010 Dec 10.

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).

Design and 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Blast Crisis / genetics
  • Blast Crisis / pathology
  • Blast Crisis / therapy*
  • Combined Modality Therapy
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Daunorubicin / administration & dosage
  • Daunorubicin / adverse effects
  • Dose-Response Relationship, Drug
  • Exanthema / chemically induced
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Imatinib Mesylate
  • Karyotyping
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Prospective Studies
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Cytarabine
  • Imatinib Mesylate
  • Daunorubicin

Associated data

  • ClinicalTrials.gov/NCT00219765