Introduction. In Russia, within the framework of the GIPAP program, in the period from 2001 to 2007 at the National Medical Research Center for Hematology, imatinib therapy was initiated in 235 patients in the chronic phase of chronic myelogenous leukemia (CML).Aim: to analyze the long-term results of therapy in patients with CML who started imatinib therapy as part of the GIPAP program.Methods. A retrospective analysis of the results of therapy was performed in 235 patients with СР CML, who received imatinib under the GIPAP program from 2001 to 2007 at the National Medical Research Center for Hematology. The protocols for therapy and monitoring of the residual disease of patients at various time intervals were determined by the clinical recommendations relevant at that time in the conditions of real clinical practice and the possibilities of the patient’s region of residence. Overall survival and survival without discontinuation of imatinib therapy, univariate and multivariate analysis of overall survival were performed. The cumulative incidence of responses was calculated. An analysis of response factors, the probability of death from concomitant diseases and death from CML was carried out.Results. The median follow-up of living patients at the time of analysis was 17.3 years (IQR 15.5–18.5). 70 (30 %) patients died, with the median time to death from the start of therapy being 7.8 years (IQR 3.7–13.6). The overall 10-year, 15-year and 20-year survival rates were 82 %, 74 % and 62 %. The cause of death in 43 cases (61%) was the progression of CML to the phase of acceleration or blast crisis and death out of remission for an unspecifi ed cause. 27 (39%) patients died from causes not related to CML. Patient age at initiation of imatinib therapy, length of time from diagnosis to initiation of imatinib therapy, and Sokal and ELTS risk groups at disease onset were identifi ed as signifi cant for survival by univariate analysis. Multivariate analysis showed independent predictive value for overall survival for age at initiation of imatinib therapy, length of illness before imatinib treatment, and ELTS risk group at disease onset. Among patients who died from CML progression, the proportion of patients who did not achieve CCyR for the entire period of therapy before death was 83% (35/42), while among patients who died from concomitant diseases, the proportion of patients without CCyR for the entire period of therapy was 11 % (p < 0.0001). The median duration of imatinib therapy was 11.4 years (0.8–21 years). 40 people died during imatinib therapy, 103 patients are alive and continue therapy with imatinib, 92 patients received at least one second-generation of Tyrosine kinase inhibitors (TKI) (TKI2), of which 62 people are alive and continue treatment with TKI. No more than two lines of TKI therapy were received by 49 (21 %) patients, and three or more lines were prescribed to 43 (18 %) patients. The median duration of therapy after switching to TKI2 was 7.8 years (0.1–15.6 years). Overall 15-year survival after switching to TKI2 was 59 %. On therapy with imatinib, during the entire observation period, complete cytogenetic response (CCyR) was achieved in 171 patients (73 %), another 18 patients (8 %) achieved CCyR for the fi rst time after switching to TKI2. Major (MMR) and deep molecular response (DMR) were achieved with imatinib in 129 (56 %) and 124 (53 %) patients, with TKI2 TKI2 therapy in 38 (16 %) and 33 (14 %) patients, respectively. Multivariate analysis showed an independent predictive value of only the time period from diagnosis to the start of imatinib treatment for achieving molecular responses to TKI therapy.Conclusion. After 20 years of monitoring patients on TKI therapy, we still cannot say that survival in CML is comparable to the survival of normal population. Long-term follow-up confi rms the fact that tumor reduction to at least the level of CCyR is the most signifi cant surrogate marker associated with a reduced risk of death from CML. Timely diagnosis of the disease, rapid initiation of targeted therapy and the fastest possible induction of cytogenetic and molecular responses is a very important mechanism for reducing the risk of resistant course and progression of CML.
