The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML Academic Article uri icon

Overview

MeSH Major

  • Antineoplastic Agents
  • Chromosome Aberrations
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Philadelphia Chromosome
  • Piperazines
  • Pyrimidines

abstract

  • In chronic myelogenous leukemia (CML), the development of chromosomal abnormalities in addition to the Philadelphia chromosome (clonal evolution) is considered by many to be a feature of accelerated phase (AP). Imatinib mesylate (STI571), a selective inhibitor of the Bcr-Abl tyrosine kinase, has significant activity in AP CML. As clonal evolution could allow Bcr-Abl independent proliferation, we analyzed its impact on the outcome of 71 AP patients treated with 600 mg of imatinib mesylate. Fifteen patients had clonal evolution alone (AP-CE), 32 had AP features but no evidence of clonal evolution (HEM-AP), and 24 had AP features plus clonal evolution (HEM-AP + CE). Of the AP-CE patients, 73% had a major cytogenetic response, compared with 31% of the HEM-AP patients (P =.043) and 12.5% of the HEM-AP + CE patients (P =.007). Complete cytogenetic responses were seen in 60% of AP-CE patients, compared with 31% of HEM-AP patients (P =.19) and 8% of HEM-AP + CE patients (P <.001). With mean follow-up of 11.2 months, 35% of all patients failed treatment. The lowest estimated rate of treatment failure at 1 year, 0%, was seen in AP-CE patients, compared with rates of 31% for HEM-AP patients and 69% for HEM-AP + CE patients (P =.0004). After 1 year, 100% of AP-CE patients were still alive, compared with 85% of HEM-AP patients and 67.5% of HEM-AP + CE patients (P =.01). In conclusion, in patients with clonal evolution as the sole criterion of disease acceleration, good responses to imatinib are still possible. Once patients have other signs of acceleration, clonal evolution predicts lower response rates and a shorter time to treatment failure.

publication date

  • September 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1182/blood-2002-03-0777

PubMed ID

  • 12176881

Additional Document Info

start page

  • 1628

end page

  • 33

volume

  • 100

number

  • 5