Пероральные антикоагулянты широко применяются для профилактики тромбоэмболических осложнений у пациентов после тотального эндопротезирования коленного сустава [1]. Генетические особенности пациентов влияют на эффективность и безопасность антикоагулянтов [2]. Дабигатран этексилат является прямым ингибитором тромбина, используемым в качестве профилактики венозных тромбоэмболических осложнений (ВТЭО) в Европе и России [3]. В данном исследовании оценивалось влияние полиморфизма генов ABCB1 и CES1 на пиковую и остаточную концентрацию дабигатрана у ортопедических пациентов. Материал и методы: в исследование включено 30 пациентов в возрасте от 43 до 77 лет после оперативного лечения-эндопротезирования коленного сустава. Все пациенты получали дабигатрана этексилат в дозе 220 мг/сут для профилактики ВТЭО. Генотипирование по полиморфизму генов ABCB1 и CES1 проводилось с использованием полимеразной цепной реакции (ПЦР) в режиме реального времени. Проводилось определение пиковой и остаточной концентрации дабигатрана методом высокоэффективной жидкостной хроматографии (ВЭЖХ). Результаты: обнаружено, что генотип ТТ полиморфизма С3435Т гена MDR1 ассоциируется с более высокой пиковой концентрацией дабигатрана, чем генотип CC (р < 0,1). Для полиморфизма rs2244613 гена CES1 статистически значимые результаты получены у пациентов моложе 60 лет (p < 0,05). При анализе комбинации гаплотипов по двум полиморфизмам выявлено, что наиболее часто встречающееся сочетание гаплотипов CC (rs1045642) ABCB1 / CT (rs2244613) CES1 достоверно связано с более высокой пиковой концентрацией дабигатрана по сравнению с совокупностью остальных комбинаций гаплотипов (p = 0,002). Выводы: при обследовании когорты пациентов, получающих дабигатран для профилактики ВТЭО в период эндопротезирования крупных суставов, подтверждено, что SNPs С3435Т ABCB1 и rs2244613 CES1 могут играть важную роль в изменении концентрации дабигатрана. Данных за влияние SNP ABCB1 rs4148738 на пиковую концентрацию дабигатрана не получено.

Results: Serum OPG concentrations increased throughout the study period (p = 7.26x10 -5 ) while RANKL concentrations did not change (p = 0.19). The OPG:RANKL ratio exhibited a 6.2-fold increase between Days 1 and 5. CTX-1 concentrations were lower (p = 0.006) 30 minutes after the 50 U/kg FVIII infusion. CTX-1 response for each participant was assessed using linear regression throughout the time course. Spine L1-L4 Z-score (SZ) and Hip Total Z-score (HTZ) correlate with CTX-1 response (p = 3.4x10 -4 and 0.014, respectively). The mean age of participants was 25.2 ± 2.1 at time of first study visit. Participants had a mean SZ of −0.74 ± 0.34, HTZ of −0.17 ± 0.32, Hip Neck Z-score (HNZ) of −0.16 ± 0.35, and HJHS of 20 ± 5. HTZ and HNZ decreased significantly with patient age (p = 0.027 and 0.032) while SZ and HJHS did not (p = 0.18 and 0.16). Consequently, age correction was applied to BMD comparisons. Statistical comparisons between HAL, EQ-5D-3L, and BHQ answers, BMD data, and HJHS are shown in Table 1. Summary/Conclusion: This prospective study demonstrates a relationship between FVIII deficiency and bone disease in PwH. OPG acts as a decoy ligand to RANKL, inhibiting osteoclastic bone resorption. The observed increase in OPG:RANKL ratio suggests FVIII has a direct impact on this pathway. Decreased CTX-1 concentrations following factor infusion and correlations between CTX-1 response and BMD further suggests that FVIII plays a role in moderating bone remodeling. Hemophilia-associated bone and joint pathology is associated with decreased quality of life. Correlations between BMD and questionnaire responses demonstrate that poor bone and joint health is physically limiting, causes discomfort, and negatively impacts perceptions of personal well-being. Furthermore, correlations between BMD and HJHS and ISTH-BAT responses (Table 1) illustrate a relationship between bleeding management and skeletal health. PwH with lower BMD report more nose and gum bleeds, suggesting a link between FVIII replacement and skeletal health. Bleeds in the extremities were not correlated with decreased BMD or increased HJHS, but abdominal (stomach, iliopsoas) and other bleeds were. Analysis of these data is ongoing.

Aim. To assess the efficacy and safety of using the drug Extimia BIOCAD (international nonproprietary name INN: empegfilgrastim) in order to reduce the frequency and duration of neutropenia, the frequency of febrile neutropenia (FN) and infections manifested by FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy. Materials and methods. This publication presents the interim results of a multicenter retrospective prospective observational post-marketing study of the safety and efficacy of the drug Extimia BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy (LEGERITY). The interim data analysis included 40 patients with lymphoproliferative diseases (Hodgkins lymphoma, diffuse large B-cell lymphoma, multiple myeloma, primary mediastinal large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, splenic marginal zone lymphoma), who were treated in ten research centers of the Russian Federation (Moscow, St. Petersburg, regional clinics). The median age of patients was 48 (2172) years, 13/40 (32.5%) patients belonged to the older age group (60 years). Patients had functional status on the ECOG scale of 02 and received at least 2 chemotherapy injections against the background of prophylaxis with empegfilgrastim. Empegfilgrastim was administered at a dose of 7.5 mg subcutaneously once 24 hours after the end of the administration of cytotoxic chemotherapeutic agents. Primary endpoint: frequency of neutropenia 35 degrees of severity; secondary endpoints: frequency of FN; frequency of severe infections (34 stages); frequency of antibiotic prescription; relative dose intensity of therapy of the conducted chemotherapy courses; the incidence of all adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of all serious adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of CTCAE 5.0 grade 34 HP in patients who received at least one dose of the study drug empegfilgrastim; discontinuation rate of study drug empegfilgrastim due to adverse reactions. Results. The results of this study demonstrate that the incidence of neutropenia of 3 degree of severity after the 1st cycle of chemotherapy developed in 2/40 patients (5%) and as a result of high-dose therapy (R-DHAP). Neutropenia of any severity was reported in 5/40 patients (12.5%). Cases of FN development have not been registered. Severe infections (mucositis, enteropathy, pneumonia, etc.), as well as the use of antibacterial and antifungal drugs during 1 cycle of chemotherapy and in the inter-course period after 1 cycle of therapy were not recorded in any patient. The next course of myelosuppressive therapy was not delayed due to the development of neutropenia in any of the patients during the study. Adverse events, according to the researcher, associated with the use of empegfilgrastim, were registered in 2/40 patients (5%): moderate generalized pain syndrome (diffuse pain) of 1 severity and in one case ossalgia of 2 severity. No serious adverse reactions were reported. Conclusion. The results of the interim analysis of the study demonstrate the high efficacy of the first Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim after a single administration of a fixed dose in the treatment of patients with aggressive and indolent lymphomas. The drug has a favorable tolerance profile in any age group of patients, especially in elderly patients. Administration of empegfilgrastim as a prophylaxis of neutropenia in patients with lymphoproliferative diseases receiving myelosuppressive therapy of varying intensity can reduce the burden on medical personnel, improve patient adherence to treatment, and contribute to the implementation of the therapeutic plan.

The aim of the study was to study the role of allogeneic transplantation of hematopoietic stem cells in a patient with the classic course of Hodgkin's lymphoma.Materials and methods. The work was carried out on the basis of the analysis of a clinical case of the clinic of occupational pathology and hematology of the University Clinical Hospital No. Professor V.Ya. Shustov. Examinations, a course of chemotherapy in conjunction with surgery and analysis of the results of a patient with a diagnosis of classic Hodgkin's lymphoma were carried out. Results. An unfavorable prognostic effect of a large amount of previous chemotherapy on overall survival after allogeneic HSC transplantation was revealed. According to the results of PET-CT, the patient achieved PETnegative remission of the disease after all the stages of treatment. Compared to the presented PET / CT scan of 02/07/2020, there is a positive trend in the form of the disappearance of metabolic activity in the 3rd rib on the right, the body of Th 11 and the body of the left ilium.Conclusion. The use of high-dose chemotherapy with hematopoietic stem cell transplantation makes it possible to achieve success in the treatment of patients in cases where the results of chemotherapy are unsatisfactory.

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