Introduction. The chronic myeloid leukemia (CML) patients with pre-treatment history prior to imatinib prescription, as well as irregularly taking the drug due to drug toxicity or lack of patient compliance, often have time shifting in achieving the appropriate reduction of the tumor clone. This study aims to investigate prognostic value of the tumor clone reduction rate in the CML patients who did not achieved the optimal response to imatinib therapy.
Matherial and methods. A retrospective study was performed on 301 CML patients treated with imatinib 400 mg daily after therapy with hydroxiurea, busulphan of interpheron-α for 3–161 міс. (Me=9 months). Median of follow-up was 64 months (40–120) months. The efficacy of imatinib therapy was evaluated by comparing the likelihood of achieving major molecular response (MMR), deep molecular response (MR4), progression free survival (PFS) and overall survival (OS), as well as the rate of loss of achieved response in patients who obtained tumor clone redaction to the level of complete cytogenetic response (CCyR) for different time: up to 6 months. (group 1), 7–12 months (group 2), 13–18 months (group 3), more than 18 months (group 4).
Results. The patients who achieved a CCyR at six months present higher probability of achieving a MMR at 48 months (96.9%) and MR4 at 60 months of imatinib therapy (92.2%) in comparison with patients with a delayed response. After ten years of follow-up, patients who had a delayed CCyR presented a PFS and OS rate that was similar to that of those who had an early CCyR. Patients with CCyR at 6 months do not have cases of loss of imatinib therapy response during follow-up. At the same time, in patients with CCyR delayed up to 12 months the rate of losing CCyR raised significantly, accounting for 41.4%, 20.7%, and 37.9% in groups 2, 3, and 4, respectively (p=0.029).
Conclusion. Delaying with CCyR is an unfavorable prognostic factor for achieving a MMR at 48 months and MR4 at 60 months of imatinib therapy. The probability of a 10-year PFS and OS does not depend on the time of CCyR achieving. Slow ineffective tumor clone reduction is a prognostic factor of the unstable response and increases the risk of secondary resistance to imatinib therapy.