Dasatinib treatment for imatinib resistant or intolerant patients with chronic myeloid leukaemia

J Int Med Res. 2011;39(2):337-47. doi: 10.1177/147323001103900201.

Abstract

Chronic myeloid leukaemia (CML) is a genetically associated malignancy of haematopoietic stem cells, characterized by a t(9;22) translocation that forms the Philadelphia chromosome and creates a novel fusion gene, BCR-ABL. Treatment with molecular-targeted therapy is usually initiated with imatinib, an inhibitor of BCR-ABL tyrosine kinase. Imatinib resistance is, however, observed in some CML patients, especially in those with advanced disease. Through computerized literature searches, a systematic analysis was conducted to examine the efficacy and benefits of dasatinib therapy for imatinib resistant or intolerant CML patients in the chronic phase (CP), accelerated phase (AP) and fatal blast crisis phase (BC). In terms of major haematological and cytogenetic responses, this meta-analysis showed no significant differences in dasatinib treatment between myeloid BC-CML and lymphoid BC-CML patients with imatinib resistance or intolerance. Dasatinib therapy was, however, significantly more effective in improving major haematological and cytogenetic responses for CP-CML patients than for AP-CML patients with imatinib resistance or intolerance.

Publication types

  • Meta-Analysis

MeSH terms

  • Benzamides
  • Blast Crisis / drug therapy
  • Blast Crisis / pathology
  • Cytogenetic Analysis
  • Dasatinib
  • Drug Resistance, Neoplasm*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Piperazines / adverse effects*
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use*
  • Publication Bias
  • Pyrimidines / adverse effects*
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use*
  • Thiazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Dasatinib