Effect of imatinib mesylate combined with granulocyte colony-stimulating factor on leukaemic blast cells derived from advanced-stage chronic myelogenous leukaemia patients

Acta Haematol. 2006;116(1):8-18. doi: 10.1159/000092342.

Abstract

Neutropenia is a severe adverse effect that can occur when treating patients with imatinib mesylate for advanced-stage chronic myelogenous leukaemia (CML). Therefore, we evaluated in vitro the combined effect of imatinib and granulocyte colony-stimulating factor (G-CSF) on proliferation and apoptosis of Bcr-Abl-expressing leukaemic cells to infer the safety of G-CSF administration. In KU812 and K562 cell lines, G-CSF neither stimulated their proliferation nor abolished the suppressive effect of imatinib. However, it stimulated the proliferation of blast cells in 2 out of the 5 cases with advanced-stage CML. These in vitro studies appear to provide data for the decision of G-CSF administration in combination with imatinib in the treatment of neutropenic patients with advanced-stage CML.

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / antagonists & inhibitors
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Benzamides
  • Blast Crisis / drug therapy
  • Blast Crisis / metabolism
  • Blast Crisis / pathology
  • Cell Proliferation / drug effects*
  • Drug Antagonism
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Drug-Related Side Effects and Adverse Reactions
  • Gene Expression Regulation, Leukemic / drug effects
  • Genes, abl
  • Granulocyte Colony-Stimulating Factor / antagonists & inhibitors
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Neutropenia / chemically induced
  • Neutropenia / drug therapy
  • Neutropenia / metabolism
  • Piperazines / adverse effects
  • Piperazines / antagonists & inhibitors
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / antagonists & inhibitors
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Granulocyte Colony-Stimulating Factor
  • Imatinib Mesylate