Background/Objectives: Neutrophils express the receptor for advanced glycation end products (RAGE), yet its role in antibacterial responses remains incompletely defined. This study aims to elucidate the dual functionality of RAGE as a membrane-bound signaling sensor and a source of soluble RAGE (sRAGE) in human neutrophils challenged with Salmonella typhimurium, a clinically relevant Gram-negative pathogen. Methods: Human peripheral neutrophils from healthy donors were isolated and stimulated with S. typhimurium, LPS, or fMLP. Calcium flux, ROS/RNS production, and phagocytosis were assessed using fluorescent probes and spectroscopy. RAGE expression and localization were analyzed by immunofluorescence microscopy and flow cytometry. Soluble RAGE in supernatants was quantified by ELISA, and its molecular forms were characterized by Western blotting. Results: Resting neutrophils exhibited minimal surface RAGE but a substantial intracellular pool. RAGE inhibition with FPS-ZM1 attenuated bacteria-induced Ca2+ mobilization, oxidative burst, nitrosative output, and phagocytosis, with the most pronounced defect at the pathogen-attachment stage—consistent with impaired cytoskeletal remodeling. Upon activation, neutrophils rapidly released sRAGE (peak at ~10 min) via combined metalloprotease-dependent shedding and regulated secretion of pre-formed intracellular stores. Paradoxically, FPS-ZM1 amplified sRAGE release while suppressing membrane-proximal signaling. Conclusions: Neutrophil RAGE functions as a dynamic, multi-compartmental regulator: membrane-associated RAGE licenses effector responses to Gram-negative bacteria, while concomitant sRAGE release provides a fast negative-feedback loop to limit excessive inflammation. This self-limiting circuit balances antimicrobial defense with tissue protection, and its dysregulation may contribute to pathological outcomes in acute and chronic infections.

Neutrophils are the first immune cells recruited by invading pathogens. During interaction with bacteria, neutrophils synthesize leukotriene B4, a potent chemoattractant that, in conjunction with the primary bacterial chemoattractant N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), stimulates the formation of neutrophil clusters surrounding pathogens. Hydrogen sulfide (H2S) plays a critical role in the regulation of host-bacteria interactions, and bacteria are known to use H2S in response to host-induced oxidative stress. The purpose of this study was to investigate the regulatory role of H2S in neutrophil cellular responses in an experimental model of neutrophil interaction with Salmonella typhimurium. The application of H2S donor (sodium hydrosulfide hydrate, NaSH) during the interaction of neutrophils with bacteria increased the leukotriene synthesis stimulated by the peptide fMLP. NaSH significantly suppressed the reactive oxygen species (ROS) formation in neutrophils. When phorbol-12-myristate-13-acetate (PMA) was used in cell pretreatment before the addition of fMLP, a decreased leukotriene synthesis and an increased ROS formation in cells were observed. Not producing ROS disulfide stress induced by diamide, in combination with NaSH, synergistically increased the fMLP-induced leukotriene synthesis during the interaction of neutrophils with the bacteria S. typhimurium. The data obtained demonstrate that not producing ROS disulfide stress increases leukotriene synthesis in the presence of H2S-producing compounds.

OBJECTIVE:To assess the possibilities of therapy with minimal effective doses (MED) of psychotropic drugs for mental disorders (MD) that manifest during the treatment of hematological malignancies (HM).MATERIAL AND METHODS:A prospective study was conducted at the National Medical Research Center for Hematology of the Russian Ministry of Health (Moscow), which included 204 (39.4%) men and 314 (60.6%) women (518 patients in total), aged 17 to 83 years (median 45 years), with various HM, in which the manifestation of MD occurred during the treatment of the underlying disease. To minimize the side-effects of psychotropic drugs and given the relatively mild level of MD, psychopharmacotherapy of patients was carried out mainly at MED. The severity of MD, manifested in patients, was assessed by the illness severity scale of the Clinical Global Impression (CGI) scale, and the effectiveness of the treatment was assessed by the improvement scale (CGI-I).RESULTS:Mainly mild (188, 36%) and moderately pronounced (270, 52%) MD were noted in patients with HM during the treatment of the underlying disease. Severe psychopathological disorders (60, 12%) were observed much less often. Because of psychopharmacotherapy with MED, patients experienced a very significant (97, 19%) and significant improvement (354, 68%) of their mental state, less often the improvement was regarded as minimal (67, 13%). Therefore, almost all patients showed a stable relief of MD; in 87% (95% CI 84-90) of patients, this improvement was significant.CONCLUSION:The tactics of treatment MD that manifest in patients with HM with MED of psychotropic drugs turned out to be therapeutically effective according to the results of the assessment on CGI scales.

Nucleotide substitutions in the 5 ' UTR and exon 2 of HLA-B*35:01:01:05 result in a novel allele, HLA-B*35:01:77.

Here, we demonstrate that human neutrophil interaction with the bacterium Salmonella typhimurium fuels leukotriene B4 synthesis induced by the chemoattractant fMLP. In this work, we found that extracellular ATP (eATP), the amount of which increases sharply during tissue damage, can effectively regulate fMLP-induced leukotriene B4 synthesis. The vector of influence strongly depends on the particular stage of sequential stimulation of neutrophils by bacteria and on the stage at which fMLP purinergic signaling occurs. Activation of 5-lipoxygenase (5-LOX), key enzyme of leukotriene biosynthesis, depends on an increase in the cytosolic concentration of Ca2+. We demonstrate that eATP treatment prior to fMLP, by markedly reducing the amplitude of the fMLP-induced Ca2+ transient jump, inhibits leukotriene synthesis. At the same time, when added with or shortly after fMLP, eATP effectively potentiates arachidonic acid metabolism, including by Ca2+ fluxes stimulation. Flufenamic acid, glibenclamide, and calmodulin antagonist R24571, all of which block calcium signaling in different ways, all suppressed 5-LOX product synthesis in our experimental model, indicating the dominance of calcium-mediated mechanisms in eATP regulatory potential. Investigation into the adhesive properties of neutrophils revealed the formation of cell clusters when adding fMLP to neutrophils exposed to the bacterium Salmonella typhimurium. eATP added simultaneously with fMLP supported neutrophil polarization and clustering. A cell-derived chemoattractant such as leukotriene B4 plays a crucial role in the recruitment of additional neutrophils to the foci of tissue damage or pathogen invasion, and eATP, through the dynamics of changes in [Ca2+]i, plays an important decisive role in fMLP-induced leukotrienes synthesis during neutrophil interactions with the bacterium Salmonella typhimurium.

Nucleotide substitutions in the 5′UTR and exon 2 of HLA‐B*35:01:01:05 result in a novel allele, HLA‐B*35:01:77.

Background. Autologous hematopoietic stem cell transplantation remains in demand for patients with hematological malignancies. The pool of hematopoietic stem cells is known to be heterogeneous. e studied various factors associated with previous treatment, patient and disease characteristics, as well as the composition of the C34+ pool in peripheral blood (), associated with the number of C34+ cells in the first leukocyte concentrate (LC).Aim. To determine the factors associated with C34+ , C34+ C143+ , C34+ C38– HLA-DR+/– and C34+ C38+/– HLA-DR– cells count in the first LC of patients with hematological malignancies.Materials and methods. Subpopulations of hematopoietic stem cells in the and first LC were studied in 80 patients with hematological malignancies (male to female ratio 1:1, median age 51 years). The control group included 24 healthy donors. Flow cytometry was used to determine the number of C34+, C34+ C38– HLA-DR+/–, C34+ C38+/– HLA-DR– and C34+ C143+ cells. Immunophenotyping was performed on samples of patients before mobilization and on the 1st day of leukapheresis, as well as on first LC samples on the 1st day of hematopoietic stem cells collection.Results. It was shown that the presence of early progenitor cells with C34+ C38– HLA-DR+/– immunophenotype in the before mobilization is associated with a higher first LC C34+ cells number (p = 0.003). In the presence of C34+ C38– HLA-DR+/– cells in the before mobilization, the median number of C34+ cells in the first LC was 2.6 %, and in their absence – 0.71 %. hen using granulocyte colonystimulating factor as monotherapy, the C34+ C143+ cells number in the first LC was significantly lower than when using chemotherapy and granulocyte colonystimulating factor (p = 0.03). However, the majority (9 of 16) of patients in the granulocyte colonystimulating factor monotherapy group had renal failure before mobilization. No factors associated with the number of C34+ C38– HLA-DR+/– cells in the first LC were found. In patients >60 years old, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients ˂ 60 years old, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients ˂ 60 years old (p = 0.043). In patients with infectious complications during hematopoietic stem cell mobilization, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients without them (p = 0.019).Conclusion. The first LC number of C34+ cells is associated with number of C34+ C38– HLA-DR+/– cells, i. e. cells of the early differentiation stage with a high proliferation potential. A relationship was established between C34+ C143+ cells number before mobilization and first LC C34+ cells count: in the paired model – within the borderline values (p = 0.05), and in the multifactorial covariance model – with high significance (p = 0.0033). It has been proven that with increasing patient age and in the presence of infectious complications, the number of longterm repopulating C34+ C38+/– HLA-DR– cells decreases.

Nucleotide substitutions in the 5′UTR and exon 2 of HLA‐B*35:01:01:05 result in a novel allele, HLA‐B*35:01:77.

Background. One approach to improving overall and relapsefree survival for patients with acute leukemia is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The probability of relapse after allo-HSCT in acute leukemia patients may be influenced by many factors, including the presence of minimal residual disease (MR) before allo-HSCT. Aim. To evaluate the relationship between MR presence in first complete remission and probability of relapse after allo-HSCT in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).Materials and methods. The study included 241 patients: 143 with AML and 98 with ALL (30 patients with Ph-positive leukemia, 22 patients with T-cell ALL and 46 patients with B-cell ALL) who received allo-HSCT at the National Medical Research Center for Hematology from September 2015 to July 2021. The MR analysis was performed using flow cytometry. Statistical analysis was performed using BIM SPSS v. 23 (SA).Results. Univariate event analysis revealed that in AML patients, poor prognosis was most associated with MRD-positive status before allo-HSCT (hazard ratio (HR) 10.249 (95 % confidence interval (CI) 4.137–25.388); p ˂ .0001). Multivariate analysis included MRD-positive status before allo-HSCT (HR 9.161 (95 % CI 3.513–23.652); p < 001), ELN risk (HR 4.423 (95 % CI 1.764–11.092); p ˂ 0.0034), and transplant source (bone marrow/peripheral stem cells) (HR 3.068 (95 % CI 1.188–7.924); p ˂ 0.0156). Three-year overall and relapse-free survival of AML patients in the first complete remission with MRD-positive status were statistically significantly worse than in patients with MRD-negative status (overall survival 43 % versus 78 %; p = 0.0004; relapse-free – 26 % versus 67 %; p ˂ .0001). In the univariate event analysis, it was found that MRD-positive status before allo-HSCT (HR 4.180 (95 % CI 1.333–13.112); p = 0.0142) was most associated with an unfavorable prognosis in ALL patients. In the multivariate analysis, only the MRD status before allo-HSCT was selected (p = 0.0005). The overall survival of MRD-positive ALL patients, although significantly worse, did not differ statistically significantly from that of MRD-negative patients who received allo-HSCT in the first complete remission (28 % versus 68 %; p = 0.09).Conclusion. MRD analysis before allo-HSCT helps to identify a group of patients with an extremely high risk of relapse after transplantation, which dictates the need to correct therapeutic tactics regarding the choice of donor, conditioning regimen, immunosuppressive therapy, or early prophylactic antirelapse therapy.

Nucleotide substitutions in the 5'UTR and exon 2 of HLA-B*35:01:01:05 result in a novel allele, HLA-B*35:01:77.

Introduction. The current overall effectiveness of acute myeloid leukemia (AML) treatment is largely ensured by the integration of transplantation technologies, but not all patients who are indicated to undergo transplantation of allogeneic hematopoietic stem cells (allo-HSCT) can reach this stage. Aim: to analyze the time and volume of the implementation of allo-HSCT in patients with AML in the first complete remission (1CR). Materials and methods. Between January 2020 and December 2023, 477 AML patients from 43 different regions of Russian Federation were referred to the NMRC for Hematology for the possibility of performing allo-HSCT. In this cohort patients, the following time parameters were analyzed: days from diagnosis of AML to primary treatment at the transplant center, from primary treatment to search for a donor (related or non-related), from diagnosis of AML to allo-HSCT, from achievement of 1CR to allo-HSCT. Results. 175 (36.7 %) patients, agreed upon by the Transplant Commission, were selected to undergo allo-HSCT. Of these, only 163 patients, who had allo-HSCT performed before January 2024, were included in further analysis. It was not sible to implement allo-HSCT in the other 236 agreed upon cases due to the following reasons: refusal of the patient - (46.6 %), relapse - 48 (20.3 %) patients, death - 23 (9.7 %) patients. Median time from 1CR to allo-HSCT was 6.8 (0.3- 26) months for all patients: for a related fully compatible donor 5.8 (0.5-26.0) months, for a haploid donor - 6.1 (0.3-23.5) months, in case of non-related - 8.0 (0.6-8.6) months. In 5 years, the NMRC for Hematology managed to reduce the the general allo-HSCT in 1CR for patients with AML from 6.5 months in 2018 to 5.8 months in 2023. Also, under the rent "AML-21" protocol, the time from 1CR to allo-HSCT in patients included in the multicenter study was minimized to - (0.33-11.0) months, and for AML patients from the poor prognosis group - 3.4 (0.33-8.0 months). Conclusion. In addition to achieving full, optimally - MDR-negative remission, the absence of severe concomitant pathology, and the presence of a donor, the time factor must also be considered. In order to cure more AML patients, it is necessary bring the implementation of allo-HSCT to the earliest possible date after achieving 1CR.

Background. Vascular endothelial growth factor A (VEGFA) is one of the most important factors for regulation of hematopoietic stem cells differentiation. It is involved in leukemogenesis and central nervous system (CNS) damage in acute leukemia. According to the literature, the VEGFA production by blast cells is increased, but the values of serum concentration and the associations with CNS involvement are contradictory.Aim. evaluate the VEGFA, VEGFR1, VEGFR2 concentration in serum and cerebrospinal fluid of patient with different types of acute leukemia in disease onset and during treatment.Materials and methods. The concentration of VEGFA in serum and cerebrospinal fluid was studied in 74 primary patients with acute leukemia. The comparison group consisted of 67 healthy donors. VEGFR1, VEGFR2 were studied in serum and cerebrospinal fluid in 34 patients at the onset of the disease. The comparison group consisted of 10 healthy donors. For the analysis, an enzyme immunoassay was used on a semi-automatic Personal Lab analyzer (Adaltis) and Affymetrix eBioscience human VEGF-A Platinum ELISA reagents.Results. Serum VEGFA concentration was statistically significantly lower in acute leukemia patients than that of donors (median 149.78 and 432.19 pg/ml respectively; p <0.0001). Factor deficiency was significantly more pronounced in patients with blastemia (p <0.015). During antitumor therapy, there was a tendency to increase the amount of the factor in the blood serum. Serum concentration of soluble VEGFR2 was also lower in patients than that of donors (6949.9 and 8795.9 pg/ml respectively; p = 0.0026). For concentration of VEGFR1 such deviations were not found. The concentrations of VEGFR1 and VEGFR2 in serum were higher than in cerebrospinal fluid (p <0.0001), while VEGFR1 showed a positive correlation between serum and cerebrospinal fluid concentrations. the concentration of VEGFR1 in the cerebrospinal fluid was significantly lower in patients with B-lymphoblastic leukemia/lymphoma compared to other types of leukemia.Conclusion. the concentration of VEGFA in serum decreases in patients with blastemia, this may indicate a lack of secretion and excessive consumption of the factor by blast cells with a decrease in the proportion of leukocytes that normally secrete the factor. In the cerebrospinal fluid, the concentrations of VEGFR1 and VEGFR2 are lower than in serum, with the lowest values being found in patients with B-lymphoblastic leukemia/lymphoma, but no relationship with the development of CNS involvement was found.

Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with Salmonella typhimurium. The scavenging of mitochondrial reactive oxygen species by mitochondria-targeted antioxidants MitoQ and SkQ1, as well as inhibition of their production by mitochondrial inhibitors, inhibit the synthesis of leukotrienes regardless of the cessation of oxidative phosphorylation. On the contrary, antioxidants N-acetylcysteine and sodium hydrosulfide promoting reductive shift in the reversible thiol-disulfide system stimulate the synthesis of leukotrienes. Diamide that oxidizes glutathione at high concentrations inhibits leukotriene synthesis, and the glutathione precursor S-adenosyl-L-methionine prevents this inhibition. Diamide-dependent inhibition is also prevented by diphenyleneiodonium, presumably through inhibition of NADPH oxidase and NADPH accumulation. Thus, during bacterial infection, maintaining the reduced state of glutathione in neutrophils plays a decisive role in the synthesis of leukotriene B4. Suppression of excess leukotriene synthesis is an effective strategy for treating various inflammatory pathologies. Our data suggest that the use of mitochondria-targeted antioxidants may be promising for this purpose, whereas known thiol-based antioxidants, such as N-acetylcysteine, may dangerously stimulate leukotriene synthesis by neutrophils during severe pathogenic infection.

Topic: 35. Quality of life and palliative care Background: Treatment adherence is able to change significantly under the influence of mental disorders that affects the results of treatment. Aims: To study the effect of anxiety and depressive disorders on treatment adherence in patients with hematological malignancies (HM). Methods: The study included 117 patients: 51 men and 66 women, aged 19 to 67 years, with Hodgkin’s lymphoma (HL) - 88, acute lymphoblastic leukemia (ALL) - 16 and aplastic anemia (AA) - 13 patients. When examining patients, the Brief Psychiatric Rating Scale (BPRS) was used, as well as some psychometric methods. Results: Anxiety and depression were detected in 36 (40.9%) patients with HL, 8 (50%) with ALL and three (23.1%) in the AA group. It was found that the medium treatment adherence (51-76% likelihood of adherence to treatment recommendations as measured by Quantitative Treatment Adherence Scale (COP25)) was in 2/3 of patients, low (50% or less) and high (76% or more) - in the remaining 1/3 of patients. With medium and low adherence to treatment, the risk of developing adverse events increases by an average on 1.7 folded. Treatment adherence is significantly higher in patients of older age groups (over 45 years). Pessimism and disruption of social ties were negatively correlated (p =0.05 and p = 0.03 respectively) with treatment adherence. A significant positive correspondence with treatment adherence was found with the following types of attitudes towards the disease: anosognosic, hypochondriac and egocentric, and a significant negative correspondence with anxious, melancholic and dysphoric types of attitudes towards the disease. Summary/Conclusion: Anxiety and depression contribute to a decrease in the adherence of patients with HM to treatment. Correction of such psychopathological disorders and improvement of adherence should be carried out jointly by hematologists and mental health professionals. Keywords: Treatment, Depression, Hematological malignancy

Aim. To identify the characteristics of T-helper subpopulations in healthy donors and to compare them with those reported in acute leukemia patients 6 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. The study enrolled 41 blood donors and 49 patients after-HSCT. The median age of donors was 36 years (range 20–60 years), 29 of them were men and 12 were women. The median age of patients was 37 years (range 19–62 years), 18 of them were men and 31 were women. Acute myeloid leukemia was diagnosed in 27 (55 %) patients and acute lymphoblastic leukemia/lymphoma in 22 (45 %) patients. Myeloablative conditioning was administered to 4 (8 %) patients and reduced intensity conditioning to 45 (92 %) patients. T-helper subpopulations were studied in the blood of healthy donors vs. acute leukemia patients after allo-HSCT. The flow cytometry analysis was conducted to simultaneously assess the expression of markers CD3, CD4, CD8, CD25, CD45RA, CD197, CD28, CCR4, CCR6, CCR10, CXCR3, and CXCR5 in T-cells. Results. The study demonstrated that the count of T-helpers at different stages of differentiation (regulatory, naive T-cells, memory cells, and effector cells) comprehensively distinguishes healthy donors from patients. Moreover, the functional structure of each of these populations differ in donors vs. patients even on Month +6 after allo-HSCT. Donors appeared to have more polarized cells among the central memory T-helpers. The proportion of T-helpers type 1 among the effector cells was higher is patients. Conclusion. The results of the study indicate that the Т-cell parameter set can be analyzed to assess immunity and to describe its disorders in different pathologies or after drug chemotherapy.

Aim. To establish the features of the influence of anxiety and depressive disorders on treatment adherence, as well as to clarify the factors associated with it in hematologic malignancies patients. Materials and methods. The study included 117 patients: 51 men and 66 women, aged 19 to 67 years, with Hodgkin's lymphoma 88, acute lymphoblastic leukemia 16 and aplastic anemia 13 patients. Patients were examined by psychiatrist using the Brief Psychiatric Rating Scale, as well as some psychometric methods. Results. Anxiety-depressive spectrum disorders were detected in 36 (40.9%) patients with Hodgkin's lymphoma and 8 (50%) with acute lymphoblastic leukemia, in the aplastic anemia group there were three (23.1%) of such patients. It was found that the average adherence to treatment was in 2/3 of patients, low and high in the remaining 1/3 of patients. With medium and low adherence to treatment, the risk of adverse events increases by an average of 1.7 times. The adherence to treatment it is significantly higher in patients older than 45 years. Signs of depression that negatively correlated with adherence to treatment were pessimism and disruption of social ties. Adherence to treatment significantly positively correlates with the following types of attitudes towards the disease: anosognosic, hypochondriac and egocentric, and significantly negatively correlates with the following types of attitudes towards the disease: anxious, melancholic and dysphoric. Conclusion. Anxiety/depressive disorders contribute to reduced adherence of hematologic malignancies patients to treatment. Their correction and increased adherence should be carried out jointly by hematologists and mental health professionals.

Introduction . Transfusions of donor blood components are indispensable in providing medical care for a large number of conditions and diseases. Therefore, the issue of improving the quality and safety of transfusions is relevant for healthcare worldwide. Aim — to assess the quality of donor blood screening for HIV, HBV and HCV by PCR in several Russian blood banks. Methods : PCR, CLIA and ELISA. Results. A study was conducted to assess the quality of molecular screening of donated blood in medical organizations, which was carried out in two stages. Two different kits of control samples for each project stage were created and delivered to the project participants (blood banks). Each kit contained samples with or without HBV DNA / HIV RNA / HCV RNA. The first stage’s kit contained 40 samples, the second one — 10 samples. Thus, project participants performed 13 series of test runs (520 tests) on the first stage and 8 series of runs (80 tests) on the second one. The number kits copies sent to one participant was determined by the participant’s laboratory equipment. Participants who used the Cobas performed 330 tests, of which 255 were incorrect. Participants using the Procleix performed 40 tests, and 29 tests gave a false result. 140 samples were tested by AmpliSens, and results in 86 cases were incorrect. One participant used Vector-Best test kits and performed 40 tests, 16 of which returned incorrect. In total, 355 samples containing HBV DNA, 121 samples containing HCV RNA, and 82 samples containing HIV RNA were provided to project participants. HBV DNA was detected in 191 (53.8 %) of 355 samples, HCV RNA was detected in 119 (98.3 %) of 121 samples, and HIV RNA was detected in 76 (92.7 %) of 82 samples. Conclusion . The proportion of inconsistencies in the results increased depending on the decrease in the concentration of the marker being determined. Participants demonstrated the best performance results if they were using branded equipment. Such participants received the least inconsistencies. The biggest issue concerned HBV DNA detection due to a lower viremia of this pathogen. All samples with low HBV DNA levels contained anti-HBc, which indicates potential latent HBV. Therefore, it is appropriate to include anti-HBc in the routine screening of donated blood.

Background. COVID-19 required fundamental changes in healthcare management, also in medical care for oncological and hematological patients. Visits to healthcare organizations were minimized, 75 % of doctor appointments were converted to telemedicine consultations. The solutions aimed at preventing further spread of COVID-19 included establishing of observational units, distinguishing between patient and employee flows, regular SARS-CoV-2 RNA testing, reducing hospital stays and transferring patients with positive COVID-19 tests to the remodeled hospitals specializing in the novel coronavirus infection, as well as providing only emergency medical treatment and, as far as feasible, converting systemic chemotherapy to per os treatment, etc. Aim. To assess SARS-CoV-2 RNA detection dynamics at the National Research Center for Hematology from April 2020 to January 2022 during the implementation of epidemic control measures. Materials & Methods. The study was based on SARS-CoV-2 RNA testing of naso- and oropharyngeal samples obtained from patients and employees of the National Research Center for Hematology (hereafter referred to as Center). Besides, bronchoalveolar lavage fluid, lung tissue biopsies, and sputum were examined for SARS-CoV-2 RNA. The study was performed at the Center’s Virusology Department with the use of Sintol reagent kit “ПЦР-РВ-2019-nCov”. Results. The study was based on 107,470 tests: 58,141 (54 %) of employees and 45,126 (46 %) of patients; 35,508 (33 %) of men and 71,962 (67 %) of women. In 1318 cases SARS-CoV-2 RNA was detected which accounted for 1.15 % of total test number. In the groups of employees/patients, virus detection rate was 1.42 %/1.09 % (p < 0.001), and in male/female groups it was 1.3 %/1.2 %, respectively (p = 0.154). The rate of infection in the groups of tumor and non-tumor hematological patients, as proved by SARS-CoV-2 RNA testing, was 1.24 % and 0.92 %, respectively (p = 0.147). In employees and patients of the Center, a wave-like virus detection rate was observed. The largest number of infections was registered in April-June 2020 (79 patients and 170 employees), October-December 2020 (126 patients and 190 employees), and January 2022 (59 patients and 203 employees), which corresponded to the first, second, and fifth COVID-19 waves in Russia. Conclusion. The analysis of data obtained at the National Research Center for Hematology demonstrated a wave-like SARS-CoV-2 RNA detection rate in employees and patients of the Center, which corresponded to the general trend in Russia. The SARS-CoV-2 RNA detection rate did not depend on sex of subjects under study and was not significantly different in the groups of tumor and non-tumor hematological patients. Although the patients in hematological hospital are more exposed to the risk of severe infectious complications, they showed laboratory markers for COVID-19 less frequently than the Center employees.

Despite their widespread clinical implementation, chimeric antigen receptor T-cell (CAR-T) therapy products, including those manufactured by industrial processes, are still not legally available or used in the Russian Federation. The aim of the study was to describe the current challenges associated with specific aspects of CAR-T manufacturing in the Russian Federation and the potential ways to overcome them. This article discusses the regulatory, legal, organisational, and methodological challenges of CAR-T manufacturing. It analyses differences in the interpretation of CAR-T therapy products under national and supranational law. According to Russian Federal Law No. 180-FZ “On Biomedical Cell Products” of 23 June 2016, CAR-T therapy products are considered biomedical cell products. However, according to Decision No. 78 of the Council of the Eurasian Economic Commission “On the Rules of Marketing Authorisation and Assessment of Medicinal Products for Human Use” of 3 November 2016, CAR-T therapy products are considered advanced therapy medicinal products (ATMPs). This article provides a detailed overview of the difficulties in obtaining starting biological materials (i.e. the inability to consider the patient as a donor) and transferring the materials for CAR-T manufacturing (i.e. the inapplicability of national law). In addition, this article describes export aspects specific to biological materials. The authors reckon that CAR-T therapy products should be categorised as ATMPs and that the corresponding active pharmaceutical ingredients, genetically modified autologous lymphocytes, should be defined as starting materials. Therefore, genetically modified autologous lymphocytes should be regulated under the requirements for starting materials for the manufacturing of active pharmaceutical ingredients that are set forth in Decision No. 77 of the Council of the Eurasian Economic Commission “On the Adoption of the Rules of Good Manufacturing Practice of the Eurasian Economic Union” of 3 November 2016. In conclusion, the authors recognise the need for national and supranational law harmonisation. For this task, it is necessary to establish expert groups that will include clinicians, legal experts, and representatives from the relevant authorities and the pharmaceutical industry.

Background. HLA-typing and matched donor selection as well as the detection of donor-specific anti-HLA antibodies are essential for allogeneic hematopoietic cell transplantation (allo-HSCT). In accordance with the guidelines of the Center for International Blood and Marrow Transplant Research (CIBMTR) optimal HLA-typing is performed on 11 HLA genes (-A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1, and ‐DPB1) with an adequate coverage aiming to obtain the values at the two-field level. Aim. To assess the results of multi-locus HLA-typing in bone marrow/hematopoietic cell donors from the database at the National Research Center for Hematology in terms of their conformance with the CIBMTR guidelines for allo-HSCT and to analyze the frequency and distribution of HLA alleles and multi-locus HLA haplotypes. Materials & Methods. The study enrolled 3485 donors who were HLA-typed by next-generation sequencing. Results. In all donors, the alleles of HLA class I genes were identified at the fourth-field level (nucleotide sequence). When the results were reduced to the second-field level (amino acid sequence), 61 HLA-A, 92 HLA-B, and 49 HLA-C alleles were detected. The alleles of class II genes were discovered either at the two-field or high-resolution levels. Among the HLA-DRB locus genes, 57 DRB1, 11 DRB3, 6 DRB4, and 5 DRB5 alleles were identified. Also, 23 HLA-DQA1, 30 HLA-DQB1, 14 HLA-DPA1, and 33 HLA-DPB1 alleles were detected. There were reported 3289 different HLA haplotypes of A-B-C-DRB1-DQA1-DQB1-DPA1-DPB1 genes. Conclusion. The database created at the National Research Center for Hematology includes potential bone marrow/hematopoietic stem cell donors typed for 11 classical polymorphic genes HLA-A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1, and -DPB1, which is in line with the guidelines of CIBMTR. The frequency and distribution of HLA alleles and multi-locus HLA haplotypes in our donors correspond to those in populations of European origin. HLA-typing and donor selection with regard to 11 HLA genes will contribute to improving the outcomes of both unrelated and haploidentical HSCTs.