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

<jats:p><jats:bold>Summary.</jats:bold> 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 <jats:italic>BCR‐ABL/ABL</jats:italic> 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 <jats:italic>BCR‐ABL/ABL</jats:italic> 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 (<jats:italic>P</jats:italic> < 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 (<jats:italic>P</jats:italic> < 0·001). Patients who achieved these falls in their <jats:italic>BCR‐ABL/ABL</jats:italic> ratio at either 4 weeks or 3 months had a superior progression‐free survival at a median follow‐up of 16·5 months (<jats:italic>P</jats:italic> = 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 <jats:italic>BCR‐ABL/ABL</jats:italic> ratio may be clinically useful for the early identification of patients destined to fare poorly on imatinib.</jats:p>