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Introduction. One of the main causes of treatment failure after allogeneic hematopoietic stem cells transplantation (alloHSCT) for acute leukemia (AL) is disease relapse. In recent years, multiparameter fl ow cytometry (MPC) has been widely used to detect minimal residual disease (MRD) because of its capacity to identify patients with a high risk of relapse due to availability and the ability to obtain results in a timely manner.Aim — to evaluate the prognostic value of MRD status before allo-HSCT and the effect of donor type and conditioning intensity on long-term results of allo-HSCT of MOB-positive patients.Patients and methods. The analysis included 107 patients with acute myeloid leukemia (AML) and 63 patients with acute lymphoblastic leukemia (ALL) who underwent allo-HSCT between September 2015 and June 2020. All patients were in complete morphological remission before allo-HSCT. At the time of allo-HSCT 91 patients with AML and 37 patients with ALL were in the first complete remission (CR), in their second and more than two CRs were 16 and 26 patients, respectively. The median follow-up was 18 (1.5–48) months for AML and 14 (1.8–60.1) months for ALL. Immunophenotypic study was performed before allo-HSCT. MRD was detected using a combination of the “different from normal” method and the search for cells with a leukemia-associated immunophenotype.Results. The disease status at the time of transplantation and the presence of MRD before allo-HSCT were independent factors infl uencing the probability of relapse (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304) and post-transplant mortality (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304). In univariate analysis, the relapse-free survival of MRD+ patients with AL in the first CR was significantly worse than in MRD– (AML: 23 % versus 57 %, p < 0.0001, ALL: 34 % versus 61.7 %, p = 0.0484), and the probability of relapse in MRD+ patients was significantly higher (AML: 75 % versus 12 %, p < 0.0001, ALL: 57 % versus 7 %, p = 0.0072). Pre-transplant MRD status was not prognostically significant for AL-patients in the second and third remission. The development of chronic GVHD reduces post-transplant mortality if it does not require systemic therapy with glucocorticosteroids (HR = 0.006, 95% CI: 0.008–0.446).Conclusion. Testing for MRD of patients with AL in the first CR before allo-HSCT is necessary for risk stratification and identification of patients who will need preventive post-transplant therapy in order to prevent disease relapse.

Among the cardiological material of our Clinic, we encountered the following completely unusual case, which we had the opportunity to observe.

Indications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with primary myelofibrosis are intermediate-2 and high-risk group of DIPSS (Dynamic International Prognostic Scoring System), beginning of the disease in childhood. The other adverse factors affect engraftment and survival after allo-HSCT, example partialy matched donor. But the result of allo-HSCT from matched related donors and result of allo-HSCT from haploidentical donors are comparable. The method for haploidentical hematopoietic stem cell transplantation is T-cell-depletion. This is clinical case of T-cell-depleted haploidentical hematopoietic stem cell transplantation in patient with primary myelofibrosis, the diagnosis was established in childhood.Показанием к трансплантации аллогенных гемопоэтических стволовых клеток (алло-ТГСК) у пациентов с первичным миелофиброзом является их принадлежность к группе промежуточного-2 и высокого риска. Пациентам с низким или промежуточным-1 риском с дебютом заболевания в детском возрасте также целесообразно рассмотреть включение алло-ТГСК в программу терапии. Перед алло-ТГСК необходимо учитывать наличие других неблагоприятных факторов, которые могут повлиять на приживление трансплантата и выживаемость после алло-ТГСК, например выполнение алло-ТГСК от частично-совместимого донора. При этом результаты нескольких исследований свидетельствуют о том, что алло-ТГСК от родственных полностью совместимых и гаплоидентичных доноров сопоставимы. Одним из подходов к выполнению трансплантации гаплоидентичных гемопоэтических стволовых клеток является T-клеточная/CD19-деплеция. Представлен клинический случай алло-ТГСК с T-клеточной/CD19-деплецией больному первичным миелофиброзом, у которого диагноз установлен в детском возрасте.

Introduction. Mutations in the TP53 gene in patients with mantle cell lymphoma (MCL TP53+) are associated with a low response to intensive chemotherapy (CT) and adverse outcomes. Allogeneic haematopoietic stem cells transplantation (allo-HSCT) is a curative approach in MCL-TP53+ patients.Aim. Efficacy and safety assessment of allo-HSCT in MCL-TP53+ patients.Main findings. During 2016–2020, allo-HSCT in MCL TP53+ was performed in three patients. Two of them were grafted from HLA-identical unrelated donors, and one — from a haploidentical donor. Pre-transplant conditioning was “fludarabine + treosulfan + melphalan” in one case, and “fludarabine + busulfan” — in the other two. In three patients, leukocyte and platelet counts were recovered at days +18 and +20, +17 and +21, +19 and +16 after allo-HSCT, respectively. Acute graft-versushost disease (aGVHD) was observed in all patients (grade I — in 2 patients, grade IV — in 1 patient). One patient developed chronic GVHD (cGVHD) of moderate grade. All three patients exhibited complete remission and 100% donor chimerism in allo-HSCT follow-up of 6, 15 and 40 months, respectively.

The purpose of this article is to identify and analyze the ideas currently available in world science and practice among foreign researchers on the Social Credit System (SCS). The article analyzes the basic principles of SCS, which allowed us to draw the following conclusions: the social credit system for China is very close to ours mentally and historically, it fits well with the management paradigm based on the principles of Confucianism and Taoism, its main task is to promote the formation of citizens’ behavior based on openness, following rituals.The main conclusions are made, such as the fact that this system allows you to put into practice the principle of the golden mean, that the application of SCS will contribute to the formation of citizens’ behavior on the basis of openness, following rituals and the desire for peace of mind. The formation of the population’s habit of living in the context of SCS, as the authors believe, will help to increase the sincerity of life. An analysis of the materials of foreign researchers was carried out in the article, which gave reason to conclude that the social credit system, launched in China, so far scares the rest of the world. In this regard, the article discusses the five main fears associated with SCS, as well as the five advantages of introducing this system, draws conclusions, and develops recommendations.

Background Chronic infection by HIV evolves with a vascular inflammatory action causing endothelial dysfunction. The action of the virus as well as the side effects of antiretroviral drugs contributes to the progression of cardiovascular diseases. The study aimed to characterise the changes of the structure of the coronary wall and the thickening of the intima by Optical Coherence Tomography in HIV-infected patients with or without symptoms of coronary heart disease. Methods Fifty-two HIV-infected individuals had a mean age of 49.8±11.4 years. There were 75% men, diabetes 30,8%, hypertension 30,8%, smokers 34,62% and 7,7% with cholesterol levels ≥99 mg/dl. Control group included 120 non-HIV-infected controls with coronary heart disease. All the participants from HIV-group receive ART, 100% of participants had plasma HIV RNA Results The average diffuse homogeneous thickening of the intima in patients with HIV was 0.67±0.24 mm, and 0.34±0.18 mm in control group, with normal values not exceeding 0.05 mm. There was impaired three-layer structure of coronary wall in 90,4% (47 of 52) HIV-infected participants and in 60% of control group, atherosclerotic plaque had only 34,62% of HIV group. All HIV-infected patients receive ART more than 5 years. Conclusion The coronary angiography and OCT demonstratedthat the inflammatory process resulting from HIV-infection or HAART may be relevant in the changes of coronary arteries in HIV-positive patients. The changes are predominantly represented by thickening of the intima, impaired three-layer structure of arterial wall and accelerating atherosclerosis. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Russian National Research Medical University named after N.I. PirogovCentral Clinical Hospital of Russian Academy of Science, Moscow, Russia

Objective. To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. Materials and methods. Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses “7+3” with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. Results. The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 and 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. Conclusion. Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

Context: The independent influence of pre-transplant MRD status on the results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is now being widely reported. The genetic and immunophenotypic diversity of AML is a problem for monitoring MRD in daily clinical practice. The most widely used methods for assessing MRD are multiparametric flow cytometry (MFC) and PCR. Objective: To assess the impact of pre-transplant MRD status determined by MFC or PCR on the long-term results of allo-HSCT. Patients and Methods: The study included 106 patients with AML in the 1st CR who underwent allo-HSCT in our center from September 2015 to December 2020. The median follow-up was 19.5 (1–50) months. Eleven-color MFC was performed on bone marrow samples obtained before allo-HSCT. In 46 out of 106 patients who had molecular markers (NPM1, FLT3, RUNX1-RUNX1T1, MLL, or CBFβ-MYH11), the MRD status was determined using PCR also. Cox proportional hazards models were used to assess the influence of various independent factors on the probability of relapse (PR). The factors included in the model were ELN risk, donor type, conditioning regimen, graft source, pre-transplant MRD status, and age. The probabilities of DFS and relapse were estimated using the Kaplan-Meier method. Results: Out of 106 patients, 22 were identified as MRD+ MFC, 84 patients were MRD- MFC, 16 patients were MRD+ PCR, and 30 patients were MRD- PCR. Statistical analysis revealed significant differences between MRD+ and MRD- patients, regardless of the research method: patients with MRD+ status had the worst DFS (MFC: 24% versus 64%, p 40 y (HR=7.006) were independent factors influencing the probability of relapse. Conclusions: MRD, regardless of whether it is determined by MFC or PCR, ELN risk, and older age are independent predictors of disease recurrence risk. The study of MRD in AML patients before allo-HSCT can be used to stratify the risk of allo-HSCT and identify patients who need prophylactic post-transplant therapy to prevent disease relapse.

The use of complex non-drug technologies at the stage of rehabilitation of metabolic syndrome (MS) includes multifactorial correction of its main manifestations: abdominal obesity, insulin resistance, arterial hypertension and dyslipidemia. A prospective randomized study on the use of low-calorie diet (LCD) and nutraceutical correction of the nutritional status of patients with MS was carried out.To study the effect of a non-drug complex including LCD, physical exercises, as well as correction of the gut microbiome and hepatic protection in relation to reduction of visceral fat volume in abdominal obesity and the dynamics of lipid and carbohydrate metabolism hormones in metabolic syndrome.120 patients with MS were randomized into 2 groups: Group 1 received LCD, physical exercises in the gym, and physical activity like daily walking up to 3-5 km/day. Group 2 received LCD, physical exercises in the gym, physical activity like daily walking up to 3-5 km/day, as well as nutraceutical correction of increased appetite, gut probiotic composition, hepatic protection. The treatment duration was 4 weeks. Anthropometric methods in order to control the body weight, waist and hip circumferences and bioimpedansometry were used.As a treatment result, patients in group 1 represented a reduction in body weight, lean and active cell mass, a decrease in musculoskeletal mass and a decrease in total fluid due to extracellular fluid. A decrease in total cholesterol and blood triglyceride fraction was noted. Leptin decreased by 13.96%. Patients of the 2Thus, LCD accompanied by nutraceutical correction of the gut microbiota and hepatic protection can be effectively used in combination with physical training in order to reduce the fat mass without pre-sarcopenia development that was confirmed by positive dynamics of volume indices, bioimpedance measurements and reduction in leptin and insulin expression.Применение комплексных немедикаментозных технологий при метаболическом синдроме (МС) включает мультифокусную коррекцию основных его проявлений: абдоминального ожирения, инсулинорезистентности, артериальной гипертензии и дислипидемии.Изучение влияния немедикаментозного комплекса, включающего низкокалорийную диету (НКД), физические упражнения, а также нутрицевтическую коррекцию микробиома кишечника и гепатопротекцию, на редукцию висцеральных жировых отложений при абдоминальном ожирении и динамику гормонов липидного и углеводного обменов при МС.Обследованы 120 пациентов с МС, которые были рандомизированы на две группы: в 1-й группе применяли НКД, лечебную гимнастику в зале и ежедневную ходьбу до 3—5 км/день; во 2-й группе — НКД, лечебную гимнастику в зале, ежедневную ходьбу до 3—5 км/день, а также нутрицевтическую коррекцию повышенного аппетита, пробиотического состава кишечника, гепатопротекцию. Длительность курса лечения составила 4 нед. Использовали антропометрические методы контроля массы тела, окружности талии и бедер и биоимпедансометрию.В результате лечения у больных 1-й группы отмечены снижение массы тела, тощей и активной клеточной массы, уменьшение скелетно-мышечной массы, а также общей жидкости за счет внеклеточной. Выявлено снижение общего холестерина и фракции триглицеридов крови. Лептин снизился на 13,96%. У больных 2-й группы наблюдалось снижение массы тела, жировой массы, тощей массы, общей и внеклеточной жидкости. Зафиксированы статистически значимое повышение активной клеточной массы, скелетно-мышечной массы, снижение общего холестерина, триглицеридов, трансаминаз. В результате снижения массы тела и уменьшения жировой массы отмечено снижение экспрессии лептина на 29,85%, уровня инсулина крови на 11,2%.Таким образом, НКД в сопровождении нутрицевтической коррекции микробиома кишечника и гепатопротекции может эффективно применяться в комплексе с физическими тренировками с целью снижения жировой массы без риска развития пресаркопении, о чем свидетельствуют положительная динамика объемных показателей, показателей биоимпедансометрии и снижение уровней экспрессии лептина и инсулина.

Context One of the main causes of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia (AL) patients is the disease relapse. Minimal residual disease (MRD) detected by multiparameter flow cytometry (MFC) is a strong prognostic marker of increased risk of relapse. Objective To determine the impact of MRD detected by MFC before allo-HSCT on clinical outcomes of acute leukemia patients. Patients and methods To assess the impact of MRD status before transplantation we included 84 AML patients and 46 ALL patients in their first or second morphologic remission who underwent allo-HSCT between July 2016 and April 2020. 6-color MFC was performed on bone marrow samples obtained before allo-HSCT. Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression on specific cell lineages at specific stages of maturation for all patients. For patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR) were estimated using the Kaplan–Meier method. Results Among 84 AML patients before allo-HSCT 23 patients (27.4%) were identified as MRD+. 11 out of 46 ALL patients (23.9%) before allo-HSCT were MRD+. Subsequently, 9 out of in 23 MRD+AML patients and 4 out of 61 MRD−AML patients relapsed (CIR 50.6% vs. 10%, p Conclusions Despite the presence of morphological complete remission before allo-HSCT, MRD persistence before allo-HSCT influences OS and RFS in patients with AL. Because of the association between MRD and relapse risk, MRD-testing before allo-HSCT may help to identify a subgroup of acute leukemia patients who need preemptive treatment.

The present state is investigated and the necessity of automation is substantiated accounting systems of budgetary institutions to ensure their effective operation. The main characteristics of accounting automation software in budget organizations are considered, as well as the main advantages of using these programs for optimization and adaptation of the accounting system of domestic institutions to contemporary challenges of the information society and international practice of budget accounting. The analysis of the functions of the most popular products used for accounting for labor remuneration for budget institutions, namely: “FIT–Budget”, “1С: Enterprise8”, “Sail–Wages”, “UA– Budget”, “IS–pro7”, “MASTER: Salary and Frames”, “Chiz–Bookkeeping: Wages”. The key requirements for companies producing software for accounting automation are substantiated. The paper deals with the problem of accounting for the calculation of wages in budgetary institutions and possible directions for solving this problem, in particular, automation of accounting systems. The advantages of the computer accounting system in the case of payroll and automation accounting in general are emphasized. Also, a list of budget institutions of Ukraine and their software is presented and the most important ways of solving the problem mentioned in the article., Исследовано современное состояние и обоснована необходимость автоматизации системы бухгалтерского учета бюджетных учреждений для обеспечения их эффективной деятельности. Рассмотрены основные характеристики программных продуктов автоматизации учета в бюджетных организациях, а также определены основные преимущества использования данных программ для оптимизации и адаптации учетной системы отечественных учреждений к современник вызовов информационного общества и международной практики бюджетного учета. Проанализированы функции наиболее популярных продуктов, которые служат для учета оплаты труда для бюджетных учреждений, а именно: "FIT-Бюджет", "1С: Пидприемство8", "Парус-Заработная плата", "UA-Бюджет", "ИС О7", " MASTER: Зарплата и кадры »,« Чиж-Бухгалтерия: Заработная плата ". Обоснованно ключевые требования к компаниям-производителям программных продуктов автоматизации бухгалтерского учета. В данные статьи освещена проблема учета расчета оплаты труда в бюджетных учреждениях и возможные направления решения этой проблемы, в частности автоматизации систем учета. Подчеркнуто преимущества компьютерной системы бухгалтерского учета в случае учета оплаты труда и автоматизации в целом. Также, приведен перечень бюджетных учреждений Украины и их программное обеспечение и самое главное пути решения указанной в статье проблемы., Досліджено сучасний стан та обґрунтовано необхідність автоматизації системи бухгалтерського обліку бюджетних установ для забезпечення їх ефективної діяльності. Розглянуто основні характеристики програмних продуктів автоматизації обліку в бюджетних організаціях, а також визначено основні переваги використання даних програм для оптимізації та адаптації облікової системи вітчизняних установ до сучасник викликів інформаційного суспільства і міжнародної практики бюджетного обліку. Проаналізовано функції найбільш популярних продуктів, які служать для обліку оплати праці для бюджетних установ, а саме: “FIT–Бюджет”, “1С: Підприємство8”, “Парус–Заробітна плата”, “UA–Бюджет”, “ІС ПРО7”, “MASTER: Зарплата і кадри”, “ЧІЖ–Бухгалтерія: Заробітна Плата”. Обґрунтовано ключові вимоги до компаній–виробників програмних продуктів автоматизації бухгалтерського обліку. У данні статті висвітлено проблему обліку розрахунку оплати праці у бюджетних установах та можливі напрями вирішення цієї проблеми, зокрема автоматизації систем обліку. Підкреслено переваги комп’ютерної системи бухгалтерського обліку в разі обліку оплати праці та автоматизації загалом. Також, наведено перелік бюджетних установ України та їх програмне забезпечення і саме головне шляхи вирішення зазначеної у статті проблеми.

Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be curative for acute myeloid leukemia (AML) patients. However, the disease relapse after allo-HSCT lead to poor outcomes almost in all cases. Minimal residual disease (MRD) is a strong prognostic marker of increased risk of relapse and reflects overall (OS) and relapse-free survival (RFS) in patients with AML. Immunophenotypic evaluation using multiparameter flow cytometry (MFC) is an important strategy for detecting MRD, because of its simplicity and wide availability. Aim. Determine the impact of MRD detected by MFC before allo-HSCT on clinical outcomes. Patients and methods. To assess the impact of MRD status before transplantation we include 56 AML patients who underwent allo-HSCT in National Research Center for Hematology between July 2016 and June 2019. Patient's characteristics are shown in table 1. All these patients were in first compete morphologic remission at the time of allo-HSCT. MRD was evaluated by MFC. Bone marrow samples were obtained before allo-HSCT and were analyzed by 6-color MFC (BD FACS Canto II, USA). Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression on specific cell lineages at specific stages of maturation for all patients. In addition, for patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of OS and RFS were estimated using the Kaplan-Meier method. Results. Among 56 AML patients before allo-HSCT (all were in CR at the time of MRD analysis). Median of follow-up was 9.3 months.11 patients (19,6%) were identified as MRD+ (0,011%-5,08%, mean 1%). And 5 of them relapsed (45,5%). Out of 45 MRD negative patients before HSCT relapse was registered in one (relapse rate 2,2%). Statistical analysis revealed significant differences between MRD- and MRD+ patients: MRD+ had much worse OS (22,9% vs. 85.5%, p=0.0047, Fig.1A) and RFS (26% vs. 97.4%, p Conclusions. Despite the presence of morphological CR before allo-HSCT, MRD persistence can lead to worse probabilities of OS and RFS, which is comparable to patients who were transplanted in relapse. Because of the association between MRD and relapse risk, it can be assumed, that testing for MRD before allo-HSCT may help to identify a subgroup of patients at high risk of relapse who might benefit from preemptive posttransplantation treatment. Disclosures No relevant conflicts of interest to declare.

Background: Nutritional problem is a key aspect of all severe diseases that always "keep in the shadows". There are different factors, such as intensive chemotherapy, constant nausea, severe infections, time for donor search that affect nutritional status in leukemia patients who underwent allogeneic stem cell transplantation (allo-HSCT). This study aimed to evaluate the impact of different "nutritional status assessment tools" on outcomes of allogeneic hematopoietic cell transplantation. Materials and methods: 307 leukemia patients who underwent allo-HSCT in National Research Center for Hematology from 2011-2019 were included on this study. Detailed patients' characteristics are given in Table 1. All data were collected directly before allo-HSCT conditioning regimen. Nutritional Risk Index (NRI) was calculated by NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight(kg)). Ideal body weight (IBW) was calculated by Lorentz IBW formula: for men IBW = (height, cm− 100) − ((height − 150)/4); for women: IBW = (height, cm − 100) − ((height, cm − 150)/2). All patients were stratified according to NRI: NRI < 83.5 - Major; 83.5 ≤NRI < 97.5 - Moderate; 97.5 ≤NRI < 100 - Mild; NRI≥100 - No risk group. Moreover all patients were stratified according to serum albumin level (more and less than 4.3 mg/dl ). Groups stratified by NRI and serum albumin was balanced for factors that can affect long-term results: disease type and status, graft source, conditioning regimen, donor's type, graft failure, acute and chronic GVHD. Data analysis was performed with R version 3.5.2 (Core Team, 2018). Chi-square and Fisher's exact test were used for contingency tables. Kaplan-Meier analysis was provided to assess the probability of overall survival. Log-rank test was used to compare two groups. Cox regression model was used to identify independent prognostic factors and its hazard ratio (HR) with a 95% confidence interval (95% CI). Age, sex, disease status before allo-HSCT (CR vs not in CR), serum albumin level (83.5 Results: As we can see on Figure 1A NRI-based stratification can't help us to predict long-term results in contrast with serum albumin level (Figure 1B). At the same time level of albumin >4.3 was associated with better results compared to serum albumin level Conclusion: These data showed that serum albumin level, but not NRI index, in leukemia patients before allo-HSCT can predict long term outcomes. Identification of these high risk patients could be a start point for future interventions and could change care protocols. Disclosures No relevant conflicts of interest to declare.

Introduction In most cases, haploidentical stem cell transplantation (haplo-HSCT) with negative depletion of α/β(+) T cells and CD19+ B lymphocytes from the graft is used to treat pediatric patients. The results are promising. However, the results of this method in adult patients is controversial. The accumulation of experience in haplo-HSCT with TCRαβ / CD19 + depletion in the group of adult patients is relevant. Aim Evaluation of the effectiveness and characterization of the most frequent complications in adult patients with hematological malignancies who underwent allo-HSCT from a haploidentical donor with depletion of TCRαβ/CD19 + cells. Patients and methods The analysis included 32 patients (14 males/18 females) with acute myeloid leukemia (AML, n=12), acute lymphoblastic leukemia (ALL, n=11), myelodysplastic syndrome (MDS, n = 6), chronic myeloid leukemia (CML, n = 1), primary myelofibrosis (PMF, n = 1), lymphoproliferative disease (LPD, n = 1). Median age was 28 years (range, 17-58). Disease status of acute leukemia at the beginning of pre-transplant conditioning was first complete remission (CR1) in 14 patients, CR2 in 7 and active disease in 2 patients. Pre-transplant conditioning regimen: RIC (Treosulfan 42 g/m2, Melphalan 140 mg/m2, Fludarabine 150mg/m2), MAC (Treosulfan 42 g / m2, Thiophosphamide 10 mg / kg, Fludarabine 150 mg / m2). Immunosuppressive therapy: Rituximab, Bortezomib, Tocilizumab, Abatacept. Immunomagnetic separation was performed using a CliniMACS Plus device. Descriptive statistics methods were used for analysis. The probabilities of survival and graft versus host disease (GVHD) rate were estimated using the Kaplan-Meier method. Results Log of TCRαβ + depletion was 1.61-5.33 (Me = 3.66). The median dose of CD34+ cells in transplant was 6.8 * 106/kg (range, 2.0-10.8). The median time to white blood cells recovery was +13 days after haplo-HSCT (range, 9-26). Median follow-up was 6.4 months. Transplant related mortality was 3.1%. Primary engraftment - 96.8%. Graft hypofunction - 16.2%. The probabilities of overall and disease-free survival for 12 months were 94.1% and 70,5%, respectively. The probability of relapse was 24.4% (Fig. 1). The probability of developing acute GVHD was 25%, GVHD rate was 18,75% including grade I (n=1), grade II (n=2), grade III (n=3) (data not shown). In 4 cases complete response was achieved with administration of first line immunosuppression therapy. 1 case (grade III GVHD) required administration of second line immunosuppression therapy - methylprednisolone, and the response was complete. 1 patient developed chronic GVHD. Nonclassical infectious complications prevail: viral infections (CMV, HHV6 and EBV) was 58.8%, fever with an unverified infectious agent was 15.6%, and tuberculosis in two cases (6.2%). Immunological events not associated with GVHD - 21.8% (TMA, TTP, myasthenia gravis, AIHA, PRCA). Conclusion In some cases, haplo-HSCT is the only HSCT option for an adult patient. The frequency of viral infectious complications and relapses in adult patients after haplo-HSCT TCRαβ / CD19 + depletion is comparable to the results in the pediatric population. Haplo-HSCT with TCRαβ / CD19 + depletion is characterized by minimal toxicity and a short period of myelotoxic agranulocytosis. Among the undesirable phenomena in the first place are infectious complications and frequent immunological events that do not fit into the criteria for GVHD, but affect the patient's quality of life and length of hospital stay. Figure 1 Disclosures Maschan: Miltenyi Biotec: Other: lecture fee.

Introduction Cytomegalovirus (CMV) reactivation is one of the main problems in allogenic hematopoietic stem cell transplantation (allo-HSCT). Standard of care for CMV-disease is still ganciclovir at 10 mg/kg b.i.d. Use of non-CMV specific intravenous immunoglobulin (IVIG) is still controversial and mostly determined by internal care protocols in every transplant center. Here we report data about impact of non-CMV specific IVIG during ganciclovir treatment in allo-HSCT CMV-patients. Patients and methods Thirty two patients with hematological malignancies transplanted in NRCH were included in this study. Detailed patients characteristics are listed in Table 1. All patients were CMV-positive by PCR (Amplisens EBV/ CMV /HHV6-screen-FL", InterLabService, Russia) and required to start therapy with ganciclovir 10 mg/kg when was included to this study. Patients in IVIG group also received non-CMV specific IVIG during ganciclovir treatment with a median total dose 20 g (7.5-90 g.). Kaplan-Meier estimator was used to determine probability of achievement of CMV-negativity from time of ganciclovir was started to CMV-negativity (by PCR) or last contact. The logrank test is used to compare differences between two groups. Fisher's exact test was used for 2×2 tables. P-value less than 0.05 was considered statistically significant Results Influence of IVIG in allo-HSCT patients on probability of achievement of CMV-negativity (by PCR) are shown in the Figure 1. As we can see there is no significant differences on the achievement of CMV-negativity (by PCR) in patients with/without IVIG during ganciclovir therapy. Conclusion The use of non-CMV specific immunoglobulins after allo-HSCT still lies in the plane of faith and the possibilities of the transplantation center than any evidence base. Using IVIG in patients after allo-HSCT is still not a routine in terms of CMV-reactivation/disease therapy and mostly based on an "experience" of every transplant center. According to our data there is no difference between IVIG/no-IVIG groups during ganciclovir treatment so use of IVIG, for our opinion, does not really make sense for CMV-disease treatment. Anyway a large randomized trial is required for determine indications for therapy with IVIG. Disclosures No relevant conflicts of interest to declare.

Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative approach for most leukemia patients. It seems that the bone marrow (BM) resident T-memory cells are the main pool for reconstitution of adaptive immunity, providing graft-versus-leukemia effect after allo-HSCT. However it has been shown previously that T-naïve cell subsets are responsible for acute graft versus host disease (aGVHD) onset. Here we report an impact of different GVHD prophylaxis on the BM resident memory T-cells recovery after allo-HSCT. Patients and methods. Our study comprised 39 leukemia patients (AML-26, ALL - 13) with a median age of 36 years (17 - 60 years old) who underwent allo-HSCT. Classical immunosuppressive regimen with CsA+MMF+MTX was applied in case of matched related (n=9) and matched unrelated (n=13) donors. Post-transplant high dose Cyclophosphamide (PT-Cy) on day +3, +4 as GVHD prophylaxis was used if allo-HSCT was performed from unrelated mismatched donors (n=8) or haplo-donors (n=4). Alfa/beta T-cells depletion was used as GVHD prophylaxis in young patients with a median age of 19 years (17-57 y.o.) who underwent haplo-HSCT (n=5). Acute GVHD grade II-III was diagnosed in 6 patients (27%) from the group with classical immunosuppressive regimen, in 2 patients (16,6%) from PT-Cy group. Acute skin GVHD grade II was diagnosed in 1 patient (20%) after T-cells depletion. Leukemia relapse was diagnosed after the day +100 in 4 patients (18%) after classic immunosuppressive regimen and 1 patient (8,3%) after PT-Cy. All 5 patients after T-cells depletion stayed in complete remission during follow-up period in 34 months after allo-HSCT. Bone marrow (BM) samples were collected on day +30, +60 and +90 after allo-HSCT in EDTA-tubes. Flow cytometry analysis was performed on BD FACS Canto II (Becton Dickinson, USA) to define T-memory subsets: T-naive and T-stem cell memory (Tnv+Tscm) - CD8+/CD4+ CD45R0-CCR7+CD28+; T-central memory (Tcm) - CD8+/CD4+ CD45R0+CCR7+CD28+; T-transitional memory (Ttm) - CD8+/CD4+ CD45R0+CCR7-CD28+; T-effector memory (Tem) - CD8+/CD4+ CD45R0+CCR7-CD28-; T-terminal effector (Tte) - CD8+/CD4+ CD45R0-CCR7-CD28-. Mann-Whitney U test was used for nonparametric data analysis. A p-value less than 0,05 was considered as significant. All data analysis was conducted utilizing SPSS ver. 23. (IBM, Chicago, Ill., USA). Results. The data are presented in the picture 1. According to our data the number of BM resident Tnv+Tscm CD8+ or CD4+ cells are much lower after alternative regimes of GVHD prophylaxis (PT-Cy or T cells depletion) on day +30 after allo-HSCT. Moreover on day +60 Tnv+Tscm CD4+ T-cells are still extremely low after T-cells depletion comparing to PT-Cy (p=0,03) and classical regimen (p=0,034). We didn't found any correlation between the number of Tnv+Tscm, Tcm, Ttm, Tem, Tte and the development of leukemia relapse or acute GVHD. Conclusion. New immunosuppressive approaches are now available for GVHD prophylaxis for patients who undergoes allo-HSCT from mismatched or haplo- donors that provides comparable results with classical immunosuppression in case of matched allo-HSCT. However Tnv+Tscm is the progenitor subset for all memory T-cells and its prompt recovery after allo-HSCT seems to be crucial for graft-versus-leukemia effect. Here we show the lowest number of Tnv+Tscm after alternative GVHD prophylaxis regimens that can be explained by more sever immunoablation. Through this it may lead to delayed reconstitution of adaptive immunity after alternative immunosuppression in patients after allo-HSCT. Disclosures No relevant conflicts of interest to declare.

Optical and electrical characteristics of different high-power multimode laser diodes with an emission wavelength of 835 nm are compared; the diodes were obtained on the basis of three systems of solid solutions: AlGaAS/GaAs, AlGaAs/GaAsP, and (Al)GaInP/GaInAsP. An output continuous optical power of 5 W is attained in lasers with a stripe width of 80 μm irrespective of the chosen material system. The highest optical power, 7 W, is attained in the lasers based on the (Al)GaInP/GaInAsP system.

Introduction. Nowadays high-dose post-transplantation cyclophosphamide (CY) replace standard immunosuppression (IST). Thereby, the investigation of T-cells reconstitution after post-transplant-CY doesn't reach appropriate level, and probably it's very different from what we see after standard IST. We studied the reconstitution of memory T-cells on day of engraftment (WBC>1000 cells\us) after allogenic hematopoietic stem cell transplantation (allo-HSCT) with post-transplant-CY and standard immunosuppression therapy. Patients and methods. During 2 years, 29 patients with different hematological malignancies were included in this study. Median of age was 36 years (24-60 years). 16 patients were males, 13 - females. 22 received RIC, 7 - myeloablative regime. Match unrelated donor (MUD) was in 17 cases, "Mismatch" MUD - 2, Match related donor (MRD) - 9, "Mismatch"MRD - 1. 4 patients were in relapse or disease progression. CY as alternative IST was administrated to 6 patients. Standard immunosuppression consisted of CSA, MMF or MTX at standard dose. Peripheral blood samples were collected in EDTA-tubes at day of engraftment after allo-HSCT (Me= 20 day (14-35)). Isolation of mononuclear cells from human peripheral blood was made by standard protocol using Lympholyte®-M Cell Separation Media (Cedarlane Labs). The anti-CD4- APC-Cy7 antibody (Becton Dickinson, USA) and FSC/SSC were used for determine population of CD4+T-cells. Anti-CD45R0- FITC (Becton Dickinson, USA) antibody were used to determine memory T-cells as subpopulation of CD4+ T-cells. Due to cyto- and lymphopenia 1,000,000 events was analyzed. Results. Mann-Whitney U test was used to test for differences between memory T-cells (CD4+ CD45R0+) after post-transplant-CY alone and in a group with standard IST. The percent of memory T-cells in CD4+ cell population at day of engraftment after post-transplant CY alone was statistically higher (74,3% ± 5,1% ,p=0.048*) than in patients with standard immunosuppression (49,4%±6,7%). Conclusion. We may conclude that patients with post-transplant CY had a different "T cell reconstitution profile". Reported data show us that probably post-transplant CY spares memory T-cells in contrast with standard IST, and also probably that CY is more selectively immunosuppressor than "gold standard" (such as CSA, MMF and etc.) not only on effector T-cells population. Despite the fact that the analyzed group is small, obtained data is important and needs further investigation. Disclosures No relevant conflicts of interest to declare.

Introduction It's generally considered that all alloimmune process such as acute graft-versus host disease (aGVHD) after allo-HSCT are mostly controlled by lymphocytes. The role of neutrophils in systemic alloimmunity after allo-HSCT is still illusive. In 1987 a distinct subset of proinflammatory, low-density granulocytes (LDGs) isolated from the peripheral blood mononuclear cell fractions of patients with system lupus erythematosus has been described. There is no LDG's in healthy donors. While the origin and role of LDGs still needs to be fully characterized, we try to describe this population in patients with hematological malignancies after allo-HSCT Patients and methods. Peripheral blood samples were collected in EDTA-tubes before allo-HSCT, on day +30,+60,+90 after allo-HSCT and at day of aGVHD from 47 patients with hematological malignancies (AML=22, ALL n=17, LPD=3, MDS =2; CML=2; 17 with active disease, 30 - in CR) after allo-HSCT (from matched unrelated donor n=34, from matched related donor n=13; MAC = 13, RIC=34). Isolation of mononuclear cells from human peripheral blood was made by standard protocol using Lympholyte®-M Cell Separation Media (Cedarlane Labs). The anti-CD66b-PE (Biolegend, USA) antibodies and FSC/SSC were used to determine LDGs cells as FSChigh \SSChigh \CD66b+. 100000 of cells were analyzed on a BD FACSCanto II (Becton Dickinson, USA). Results. Results of blood evaluation of 47 patients with hematological malignancies, whose blood was examined after allo-HSCT presented in table 1. Conclusion Despite the fact that we don't get significant differences. LDG's detection in allo-HSCT patients need further investigation. Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Disclosures No relevant conflicts of interest to declare.

Introduction Allogenic bone marrow transplantation (allo-BMT) with high-dose, post-transplantation cyclophosphamide (CY) to promote graft-host tolerance has become an alternative for standard immunosuppression. This post-BMT CY-based immunosuppression regimen has comparable efficacy with other immunosuppressive regimens including cyclosporine A and mycophenolate mofetil. Previously we reported a significant reduction of acute GVHD rate by using MSC infusion for GVHD prophylaxis (n=19, p=0.009) [Abstract 1256, 52nd ASH Annual Meeting abstract]. So we studied high-dose, post-transplantation cyclophosphamide and mesenchymal stem cells (MSC) infusion for graft-versus-host (GVHD) prophylaxis for patients with advanced disease after FLAMSA (where amsacrin was substituted for idarubicin) and FluBuATG conditioning regimen. Patients and methods 7 patients with a median age 38 years (24-59 years; 5 males, 2 females; 4 donors/recipient pairs was sex matched, 3 was sex mismatched). All patients with advanced disease (relapsed or refractory AML n=4, ALL n=2, MM n=1) with a median blast cells 17.4%, underwent allo-BMT (n=5 from HLA-identical related donor, and n=2 from unrelated donor). Conditioning regimen was composed of fludarabine, busulfan, and horse anti-thymocyte immunoglobuline for 2 patients, in 4 patients FLAMSA was applied, and 1 patient has no conditioning regimen at all (he was in profound prolonged aplasia after previous course of chemotherapy). For GVHD prophylaxis CY at dose 50 mg/kg daily at day +3 (n=2) and at day +3,+4 (n=5) was used. All patients also received MSC for acute GVHD prophylaxis at day of recovery (WBC>1*109/l) at dose 1*106/kg. No other immunosuppression was used. Results Neutrophil engraftment was achieved at a median day +20 (range from 17 to 44 days). Acute GVHD occurred in 3 patients (43%) at a median day +45; all cases were Grade 2-3 (with only skin n=2; and with skin and liver involvement n=1); there was only 1 patient with late refractory GVHD in this study treated with prednisone at a dose 2 mg/kg; all other patients responded to initial treatment with cyclosporine A at 3 mg/kg. Overall mortality rate was 42.6%. 1 patient died in CR at day +60 due veno-occlusive disease (TRM - 14%). Relapses occurred in 2 patients (28.6%) at a 3,8 and 2.4 months. The overall survival is 51.4% with a median of follow-up 3,9 month. Conclusion Despite the fact that we study small group use of cyclophosphamide with MSC for GVHD prophylaxis is a very attractive approach for patients with advanced disease, and needs further investigation. Disclosures: No relevant conflicts of interest to declare.

Elaboration of a special system of partial fixation in rats and their sensibilization to an acoustic epileptogenic stimulation after parathyroidectomy have enabled us to register bioelectrical processes of the brain in chronic conditions during all stages of audiogenic seizures.