The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia

Br J Haematol. 2003 Mar;120(6):990-9. doi: 10.1046/j.1365-2141.2003.04200.x.

Abstract

Real-time quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) is increasingly used to monitor responses in chronic myeloid leukaemia (CML). The peripheral blood BCR-ABL/ABL ratio, as assessed by Q-RT-PCR, has been shown to correlate with the contemporary cytogenetic response in patients receiving imatinib (Glivec, Gleevec). We have used Q-RT-PCR to monitor the early molecular response to 4 weeks and 3 months of imatinib therapy, in 47 patients with established CML. After 4 weeks of imatinib therapy, patients whose BCR-ABL/ABL ratio had fallen to less than 50% that of baseline had a significantly higher probability of achieving a major cytogenetic response after 6 months of therapy, when compared with those whose ratio did not fall by this amount (P < 0.001). Similarly, patients whose ratio at 3 months was less than 10% of that at baseline had a significantly higher probability of achieving a major cytogenetic remission at 6 months (P < 0.001). Patients who achieved these falls in their BCR-ABL/ABL ratio at either 4 weeks or 3 months had a superior progression-free survival at a median follow-up of 16.5 months (P = 0.01 and 0.003 respectively). These effects were independent of patient age and disease stage. The occurrence of peripheral blood cytopenias sufficiently severe to interrupt therapy was unrelated to progression-free survival. In conclusion, the data suggest that the early trend in the BCR-ABL/ABL ratio may be clinically useful for the early identification of patients destined to fare poorly on imatinib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / genetics*
  • Genetic Markers
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Proto-Oncogene Proteins c-abl / genetics*
  • Pyrimidines / therapeutic use*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Genetic Markers
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl