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

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.