Background: Recent evidence suggests that MSCs might improve survival during sepsis in animal models. However, no study has investigated the effects of MSC therapy on the survival of pts with sepsis and SS, especially severe-neutropenic pts. Aim: The aim of this study was to investigate the efficacy of the administration of MSCs for the treatment of SS in neutropenic pts. Patients and Methods: This prospective, single-center, randomized Russian clinical trial of MSCs in severe neutropenic pts with SS (RUMCESS) (NCT 01849237) was approved by the local ethics committee and was begun in December 2012. Neutropenic pts (WBC < 0.5x109/l) with SS were enrolled on to the study. The pts were randomly assigned (1:1) to receive either conventional therapy (CT) of SS (CT group), or CT plus donor MSCs at a dose of 106/kg intravenously within the first 10 hours after SS onset (CT+MSCs group). Written informed consent was obtained for all pts. All pts were admitted and treated in the ICU of the National Research Center for Hematology (Moscow). The Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sepsis-related Organ Failure Assessment (SOFA) score were employed to determine the severity of illness. Pts were followed up for 28 days after enrolment in the study, and 28-day all-cause mortality was assessed. Pts characteristics and complication rates were compared using Fisher's exact test. The Kaplan-Meier method with the log-rank test, and Cox proportional hazard regression model were used to determine the statistical significance of the relationship between overall survival (OS) and the treatment regimen. Statistical analyses were performed using SAS 9.1. Results: Of the 27 neutropenic pts with SS, 13 received CT and 14 received CT+MSCs. There were no statistically significant differences in the demographic variables between groups . The CT group included 7 males, 6 females, aged 33-81 yrs, median 55 yrs. The CT+MSCs group included 6 males, 8 females, aged 30-75 yrs, median 48 yrs. Hematological disorders were also similar in the two groups: AML (4), NHL (4), HL (1), MM (3), MDS (1) in the CT group, and AML (5), NHL (7), MM (1) in the CT+MSCs group. In all pts, except for one with MDS, neutropenia developed after chemotherapy. In 8/13 pts in the CT group and 9/14 pts in the CT+MSCs group blood cultures were found positive, mostly gram-negative. Baseline APACHE II scores (34.2 [95% CI 28.3-43.1] and 32.2 [95% CI 26.2-37.5] in the CT- and CT+MSC-groups, respectively), and SOFA scores (17.9 [95% CI 13.5-22.2] and 15.1 [95% CI 11.0-19.2] respectively), were similar in the two groups. 28-day survival rates were 15% (2 out of 13 pts) in the CT group and 57% (8 out of 14 pts) in the CT+MSCs group (P=0.04) (Figure 1). The significant increase in 28 days OS of the pts in CT+MCSs group was associated with SOFA score decrease, which was started in three days after onset of SS. Despite higher 28-day survival rates only 3 pts treated with CT+MSCs remained alive after 3 months, and 5 of 8 pts from the CT+MSCs-group who survived 28 days died later because of sepsis-related organ dysfunction. Conclusions: Administration of MSCs in the first hours of SS might improve short-term survival in neutropenic pts, but does not prevent death from sepsis-related organ dysfunction in the long term. Perhaps repeated administration of MSC is required. Figure 1. Comparison of OS rates between the two groups of pts in the ICU. There was a statistically significant increase of the 28-day OS rates (42% vs. 15%; P=0.04) and a statistically significant decrease of the risk of death (HR 0.35; 95% CI 0.13 - 0.91; P=0.04) in the CT+MCSs group vs. the CT group. Figure 1. Comparison of OS rates between the two groups of pts in the ICU. There was a statistically significant increase of the 28-day OS rates (42% vs. 15%; P=0.04) and a statistically significant decrease of the risk of death (HR 0.35; 95% CI 0.13 - 0.91; P=0.04) in the CT+MCSs group vs. the CT group. Disclosures No relevant conflicts of interest to declare.

Background. Internationally published data about the course of COVID-19 in patients with congenital bleeding disorders (CBDs) are limited. There are questions about how COVID-19 affects the course of CBDs and, conversely, how CBDs affect the course of coronavirus infection.Aim — to analyze the course of COVID-19 in patients with CBDs in Russia.Materials and methods. A cross-sectional survey was conducted at the National Medical Research Center for Hematology (Moscow) for the period from June 25 to July 31, 2022. A cluster of 187 patients from different regions and cities of Russia were interviewed with a questionnaire based on survey administration software (Google forms) containing 27 questions.Results. COVID-19 affected 115 (62 %) of 187 surveyed patients and 22 (19 %) patients suffered from coronavirus infection twice. Hospitalization was required for 14 (12 %) patients with an average age of 42 years (10 patients with severe hemophilia A, 1 patient with moderate hemophilia B, 2 patients with von Willebrand disease and 1 patient with hypoproconvertinemia). During COVID-19 bleeding was observed in 9 (8 %) patients and was represented by hemarthrosis, ecchymosis, hematomas, nosebleeds, menorrhagia, hemorrhoidal bleeding, hemorrhage in the eyeball. There were no cases of thrombosis among 115 COVID-19 patients. Among patients with CBDs who had COVID-19, compared with patients who had not COVID-19, von Willebrand disease was statistically significantly more common (p = 0.04). Changes in the course of CBD after COVID-19 were noted by 21 (18 %) of 115 patients: 11 (10 %) of those who were ill noted increased joint pain, 9 (8 %) complained of joint pain that had not been previously experienced; 10 % of patients described changes of hemorrhagic syndrome.Conclusion. The probability of hospitalization of patients with CBDs and COVID-19 older than 40 is statistically significantly higher. Von Willebrand disease can be considered as a potential risk factor for COVID-19. Given the absence of cases of thrombosis in the interviewed group of patients, the results of the study suggest that the presence of hypocoagulation in patients with CBDs may be a protective pathophysiological mechanism that prevents the development of COVID-19-associated thrombotic complications.

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Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. 1 Numerous studies have found a high prevalence

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Актуальность. Первичные лимфомы костей (ПЛК) относятся к редким экстранодальным лимфатическим опухолям. Более чем в 90 % наблюдений они представлены диффузной В-крупноклеточной лимфомой (ДВКЛ). Эффективность стандартной иммунохимиотерапии R-CHOP при локальной (IЕ) стадии ПЛК составляет более 90 %. В то же время при наличии таких факторов неблагоприятного прогноза (ФНП), как множественное поражение костей (IVЕ стадия), повышение активности лактатдегидрогеназы (ЛДГ), В-симптомы, большой размер опухоли, отмечается снижение эффективности R-CHOP. Оптимального режима противоопухолевого лечения для больных ПЛК с ФНП в настоящее время нет. Мы предлагаем у данной категории пациентов проводить первичную интенсифицированную многокомпонентную химиотерапию. Цель. Оценить долгосрочные результаты проспективного одноцентрового исследования по применению высокодозной программы mNHL-BFM-90 у больных с первичной ДВКЛ костей и ФНП. Материалы и методы. В исследование включено 33 пациента с первичной ДВКЛ костей, наблюдавшихся в ФГБУ «НМИЦ гематологии» с 2006 по 2018 г. Медиана возраста больных составила 44 года (диапазон 16-78 лет). Оценивались основные клинические, лабораторные, рентгенологические и МР-характеристики опухоли, показатели выживаемости, факторы прогноза. Результаты. ФНП выявлены у 29 (88 %) пациентов, из них распространенная (> IE) стадия была у 20 (61 %) больных, повышение активности ЛДГ -у 20 (59 %), В-симптомы -у 15 (45 %), большой размер опухоли -у 23 (71 %). Высокодозное противоопухолевое лечение по программе mNHL-BFM-90 проведено 27 из 33 больных. Общая и выживаемость без прогрессирования за 5 лет составили 92 %. Ни один из ФНП не оказал статистически значимого влияния на показатели выживаемости. Заключение. Применение высокодозной программы mNHL-BFM-90 при ПЛК, характеризующихся неблагоприятным прогнозом, позволяет достичь длительных ремиссий у 92 % пациентов. Мы рекомендуем mNHL-BFM-90 в качестве терапии выбора у прогностически неблагоприятной группы больных с ПЛК.

The first prospective study of intensive therapy for FL in Russia has demonstrated that HDCT with further auto-BSCT in first-line therapy allows complete remission in patients with poor prognostic factors and higher overall and progression-free survival rates.

BACKGROUND: Follicular lymphoma (FL) is one of the most frequent types of B-cell lymphomas and accounts for about 22% of all non-Hodgkin lymphomas in Russia. The disease is usually a long-term condition with frequent relapse. At the same time 15-20% of pts have fast-tumor progression. Patients (pts) of this group die within the first 1.5-2 years from the time of diagnosis. High-dose chemotherapy (HDT) followed by ASCT in the presence of nonfavorable characteristics of FL (fast growth of tumor volume, B-symptoms, third citological grade of tumor, large tumor size, absence of anti-tumor response to R-CHOP courses in the first remission) increases the overall survival and progression-free survival of pts. AIM: To estimate HDT with ASCT efficiency among pts with FL in front-line therapy who received treatment in the National Research Center for Hematology during 2000-2013. PATIENTS AND METHODS: The results of ASCT among 12 pts with FL have been analyzed: 8 male and 4 female aged from 31 to 50 with median age 43. Patients in the main group (11/12) were on the IVth stage of tumor growth. In 6/12 cases the tumor size was more than 6 sm. Among 7/12 pts, besides lesions of lymphatic nodes, extra nodal lesions were found: infiltration in psoas (1/12), kidney (1/12), stomach (1/12), lungs (1/12), thyroid (1/12), pancreas (1/12). In 2/12 cases leukaemization was observed. Based on FLIPI criteria all the pts were divided into three groups: in the first risk group - 5/12 pts, in the second - 3/12, in the third - 4/12. B-symptoms were in the majority of cases (9/12). 9/12 pts were diagnosed with I-II cytological grade of FL, among 3/12 - III A/B. Based on the character of tumor growth the dispersion was the following: nodular tumor growth - 5/12, nodular-diffuse tumor growth-6/12, diffuse tumor growth - 1/12. Immuno-chemical investigation of protein serum and urine was performed in 9/12 cases, and among them rising serum β2-microglobulin above the norm was observed in 4/9 pts. A rise in lactate dehydrogenase concentration above the norm was observed among 4/12 pts. Lesion of bone marrow at the beginning of the disease was identified among half of the pts (6/12). Induction courses were performed on the R-CHOP programs, with intensive therapy - on protocol mNHL-BFM-90. RESULTS: Anthracycline courses were prescribed for nearly all of the pts as an inductive therapy: R-CHOP (11/12). mNHL-BFM-90 protocol was chosen as an inductive regime because of the fast growth of tumor size, IIIB grade of FL in 1/12 case. This tumor growth behaved like diffuse large B-cell lymphoma. In three cases medical-diagnostic splenectomy was undertaken before chemotherapy. After the inductive regimes the pts were given HDT based on the following scheme: two courses R-DHAP, course with rituximab and high-doses cyclophosphamide, a course with rituximab and high doses of etoposide, R-BEAM. All 12 pts, who were given ASCT are in full remission on the main disease. The period of observation is from 13 to 164 months. CONCLUSION: This first experience of intensive therapy in FL in Russia demonstrates that ASCT as a front-line therapy leads to complete remission of FL among pts who have nonfavorable prognosis factors. Disclosures No relevant conflicts of interest to declare.