Triphasic Exponential Decline of BCR-ABL Transcripts during Imatinib Therapy for Chronic Myelogenous Leukemia.

In Japan Adult Leukemia Study Group (JALSG) clinical trial, imatinib was used as initial therapy for 171 patients with chronic myelogenous leukemia. We measured levels of BCR-ABL transcripts in the blood of all patients in this trial before and 1, 2, 3, 6 and 12 months after the treatment. Levels of BCR-ABL transcripts were measured by a quantitative real-time polymerase-chain-reaction assay. Results were expressed copy number of BCR-ABL per 1 microgram of RNA. Median number of BCR-ABL transcript was 106,478 at diagnosis and 61328, 24213, 4981, 331 and 98 at 0, 1, 2, 3, 6, 12 months after the treatment, respectively. Three log reductions were obtained 0%, 35.5% and 50.9% of patients at 3, 6 and 12 months of the treatment. Half reduction time between 0 and 1 month (0M–1M) is 1.3 M. In the next month (1M–2M), it is 0.75M and those between 2–3 and 3–4.5 months are 0.44 and 0.51. Thereafter, reduction speed is down because half reduction time is 1.5 between 4.5 and 6 months. After 6 months half time is 4.1months. This reduction curve shows the. Exponential decline value per day are 1.8%, 3.1% and 5.2% during first, second and third month, respectively. Thereafter exponential decline value is decreasing as 4.4% (3M–4.5M), 1.5% (4.5M–6M) and 0.6% (6–12M). In the previous study reported that, successful therapy leads to a biphasic exponential decline of leukemic cells (