Multidrug resistance (MDR) is a major challenge in leukemia treatment. The objective of this study was to identity predictors of MDR to allow for rapid and economical assessment of the efficacy of planned antitumor therapy for leukemia patients. The study included 113 patients with acute and chronic leukemias. Prior to antitumor therapy, we measured the sensitivity of tumor cells of patients to the panel of chemotherapeutic drugs, together with MDR1 mRNA and P-glycoprotein (P-gp) expression as one of the mechanisms of MDR, and compared these data with the response to therapy. The scales for leukemia patients according to therapy response, drug sensitivity of tumor cells, MDR1 mRNA and P-gp levels, and the presence of unfavorable immunological and cytogenetic markers were introduced for subsequent correlation analysis. We show that the drug resistance of tumor cells of leukemia patients estimated in vitro at diagnosis correlates with a poor response to chemotherapy and is usually combined with aberrant and immature immunological markers, cytogenetic abnormalities, and a high expression of MDR1 mRNA and P-gp. All together, these factors indicate unfavorable prognosis and low survival of leukemia patients. Thus, the sensitivity of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis may have prognostic value for individual types of leukemia.

Introduction. Over the past decade significant progress has been made in the treatment of patients with chronic myeloid leukemia (CML). In the most patients it is possible to reach a major molecular response (MMR) and maximize overall survival (OS). However, in real clinical practice in the regions of Russia, there is a number of unresolved problems that have led to the deterioration in the results of therapy such as, low patient compliance to treatment and the lack of proper control by doctors of polyclinics over the intake of medications and the course of the disease.   Aim — to compare the incidence and results of therapy of patients with chronic myeloid leukemia in Novosibirsk and the Novosibirsk region.   Materials and methods. The results of therapy of 333 CML patients were studied. The incidence and prevalence of disease, 5-year OS and predicted 10-year OS as well as 5-years and 10-years predicted event-free survival (EFS) have been evaluated. Results of therapy and compliance to treatment of 214 patients with CML who had been treated with imatinib for more than 18 months also were studied.   Results. The incidence from 2004 for 2020 was 0.62 per 100,000 population per year, the prevalence of CML in Novosibirsk over the past 15 years has increased from 3.27 to 10.89 cases per 100,000 population, in the Novosibirsk region – from 1.83 to 5.55 cases per 100,000 population. Median OS was not reached. The 5-year OS and 10-year OS in Novosibirsk were 85.7 and 72.5 %, respectively. The 5-year OS and 10-year OS in Novosibirsk region was 80.5 and 72.3 %, respectively. The 5-year EFS and 10-years predicted EFS in Novosibirsk was 55.8 and 40.8 %, respectively. The 5-year EFS and 10-years predicted EFS in Novosibirsk region was 34.9 and 18.7 %, respectively (p = 0.02882). The median EFS in Novosibirsk and Novosibirsk region was 6.8 and 2.7 years, respectively. Among patients treated in Novosibirsk, 134 patients (95.7 %) achieved a complete clinical and hematological response (CHR), 124 patients (88.5 %) — a complete cytogenetic response (CCyR), 95 patients (67.8 %) achieved MMR. Treatment failure was in 45 patients who did not obtain MMR and 16 (35.5 %) of 45 did not achieve even CCyR. The 2nd generation tyrosine kinase inhibitors (TKI 2) were administered to 18 patients who were resistant to imatinib. CHR was maintained in 17 out of 18 patients (94.4 %), CCyR — in 14 patients (77.7 %), MMR was achieved in 12 patients (66.7 %). In Novosibirsk region CHR was obtained in 72 of 74 patients (97.3 %), CCyR — in 50 patients (67.6 %), MMR — in 13 patients (17.6 %). No MMR was achieved in 61 patients (82.4 %), 17 (22.9 %) of them failed to obtain even CCyR. TKI 2 were administered to 7 out of these 61 patients, and 6 (85.7 %) of 7 maintained CHR, 5 patients (71.4 %) — CCyR, 1 patient (14.3 %) – MMR. Adherence to imatinib therapy was significantly lower in the group of patients with therapy failure than in patients with an optimal response both in Novosibirsk (p < 0.00001) and in Novosibirsk region (р = 0,000002).   Conclusion. We have revealed a significant increase in the incidence of CML in Novosibirsk and Novosibirsk region. The problems in treatment are as follows: insufficient control by primary care physicians over patients living in Novosibirsk region and low treatment compliance of patients.

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