Serial monitoring of BCR-ABL by peripheral blood real-time polymerase chain reaction predicts the marrow cytogenetic response to imatinib mesylate in chronic myeloid leukaemia

Br J Haematol. 2002 Sep;118(3):771-7. doi: 10.1046/j.1365-2141.2002.03705.x.

Abstract

Imatinib mesylate (trade name Glivec or Gleevec) is emerging as an important therapy in the management of chronic myeloid leukaemia (CML). It is clinically useful to monitor the cytogenetic response to imatinib, although frequent marrow examinations are inconvenient. We have used serial real-time reverse transcription-polymerase chain reaction (RT-PCR) to monitor the ratio of peripheral blood BCR-ABL to normal ABL transcripts in 43 patients receiving imatinib, and compared the results to concurrent conventional bone marrow (BM) cytogenetics. After 6 months of treatment, 13 cases were complete cytogenetic responders, defined as all BM metaphases negative for the Philadelphia (Ph) chromosome. In these patients, the BCR-ABL/ABL ratio was less than 0.08%. Six cases achieved a partial cytogenetic response (1-35% Ph-positive BM metaphases) and their BCR-ABL/ABL ratio was between 0.08 and 10%. In total, 24 cases were cytogenetic non-responders, and their BCR-ABL/ABL ratio exceeded 11%. The data suggested that the 6-month BCR-ABL/ABL ratio may reliably predict the contemporary marrow cytogenetic response. It was concluded that serial real-time RT-PCR may offer a convenient surrogate assessment of the marrow cytogenetic response to imatinib therapy in CML.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor / genetics*
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Genes, abl
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Philadelphia Chromosome
  • Piperazines / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / therapeutic use*
  • Reverse Transcriptase Polymerase Chain Reaction*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl