The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate

Cancer Genet. 2012 Nov;205(11):563-71. doi: 10.1016/j.cancergen.2012.09.003. Epub 2012 Oct 27.

Abstract

The aim of this study was to evaluate the long-term clinical significance of an additional chromosomal abnormality (ACA), variant Philadelphia chromosome (vPh) at diagnosis, and newly developed other chromosomal abnormalities (OCA) in patients with chronic myeloid leukemia (CML) on imatinib (IM) therapy. Sequential cytogenetic data from 281 consecutive new chronic phase CML patients were analyzed. With a median follow-up of 78.6 months, the 22 patients with vPh (P = 0.034) or ACA (P = 0.034) at diagnosis had more events of IM failure than did the patients with a standard Ph. The 5-year overall survival (OS), event-free survival (EFS), and failure-free survival (FFS) rates for patients with vPh at diagnosis were 77.8%, 75.0%, and 53.3%, respectively; for patients with ACA at diagnosis, 100%, 66.3%, and 52.1%, respectively; and for patients with a standard Ph, 96.0%, 91.3%, and 83.7%, respectively. During IM therapy, eight patients developed an OCA, which had no impact on outcomes as a time-dependent covariate in our Cox proportional hazards regression models. This study showed that vPh was associated with poor OS and FFS and that ACA had adverse effects on EFS and FFS. In addition, no OCA, except monosomy 7, had any prognostic impact, suggesting that the development of OCA may not require a change in treatment strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Chromosome Aberrations*
  • Female
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Piperazines / therapeutic use*
  • Prognosis
  • Pyrimidines / therapeutic use*
  • Regression Analysis
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate