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Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a decrease in platelet count, which often leads to bleeding. Evidence suggests that low platelet counts in ITP are the result of multiple factors, including impaired thrombocytopoiesis and changes in the immune response leading to platelet destruction. ITP is a heterogeneous disease with a course that is difficult to predict. In a significant number of cases, ITP becomes chronic, requiring long-term maintenance treatment, which leads to an increased risk of hemorrhagic complications and a decrease in quality of life. A deeper understanding ofthe etiology and pathogenesis ofthis disease makesit possible to identify potentialtherapeutic targets for the development of new effective treatments. This review summarizes recent advances in understanding the ITP pathophysiology, evaluating current therapeutic strategies and methods for predicting therapy response.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and decreased platelet production. The formation of antibodies to platelet and megakaryocyte glycoproteins plays a major role in the pathophysiology of ITP. All treatment strategies for ITP attempt to increase platelet count and reduce the risk of bleeding complications. Corticosteroids remain the most commonly used first-line therapy for ITP, but their long-term use is limited due to the development of severe complications. Today the new treatment methods including the use of thrombopoietin receptor agonists (TPO-RA) romiplostim, eltrombopag and avatrombopag with a number of advantages over standard therapy are of great interest. These drugs are recommended for use in the second-line therapy and show high efficacy in patients with ITP, particularly in real clinical practice. In most cases TPO-RA provide stable and long-term remission of the disease, allowing you to reduce or discontinue the use of glucocorticosteroids and avoid splenectomy. Many studies of the mechanism of action, efficacy and toxicity of TPO-RA have been performed. the research results significantly expand our knowledge about these agents. This review provides comparative data of the TPO-RA safety and the main aspects of their clinical use. The features of the new drug avatrombopag, recently approved for use in the Russian federation, are described. the overview presents the advantages and limitations of each drug, possible adverse events and methods for their control.

Glucocorticosteroids (GCS) are the first-line treatment for idiopathic thrombocytopenic purpura (ITP). Despite their high efficacy in patients with newly diagnosed ITP, an adequate level of platelets remains after GCS withdrawal in only less than 20 % of patients. Additionally, GCS use is associated with an increased risk of different adverse reactions, including serious and life-threatening ones. Thrombopoietin receptor agonists represent a relatively new class of drugs for treating ITP as a second-line therapy. This paper reviews the risks of GCS pharmacotherapy, as well as the evidence supporting the use of thrombopoietin receptor agonists as both first-line and second-line treatment for patients with ITP.

Multiple primary malignant neoplasms (MPMNs) is a complex process in which the development of 2 or more neoplasms simultaneously or after a certain interval is observed. MPMNs develop independently from each other within one or more organs. Many etiopathogenetic factors can cause MPMNs. Numerous studies have been conducted to study the effect of T-cell immunity on the development of this pathology. Today, there is a steady upward trend in the prevalence of mpmns, which, on the one hand, is due to more effective methods of early diagnosis, an increase in patient overall survival, and early antitumor therapy (chemotherapy, radiation therapy), on the other hand, this trend may be associated with pathology of T-regulatory cellular immunity. T-regulatory cells play a strategic role in the development of immune homeostasis, and their function is closely related to the occurrence of a wide range of pathologies, including autoimmune diseases and malignant neoplasms. The article presents a clinical case of a patient with a confirmed diagnosis: mpmn, immune thrombocytopenia (idiopathic thrombocytopenic purpura). On prednisolone therapy, remission was achieved for 2 metachronous tumors and a complete hematological response for immune thrombocytopenia was obtained. there were no signs of hemorrhagic syndrome and complications during prednisone therapy. It is planned to continue monitoring the patient for metachronous tumors by a hematologist, an oncologist at the place of residence, as well as at the center for orphan diseases of the Moscow Regional Research Clinical Institute named after M. F. Vladimirsky with control of platelets and general condition.

Background. Immune thrombocytopenia (ITP), or idiopathic thrombocytopenic purpura, is a hematological autoimmune disease characterized by bleeding and an isolated decrease in platelet count

Background. Idiopathic thrombocytopenic purpura (ITp) is an autoimmune disease characterized by antibody-mediated platelets destruction and impairment of their production, which manifests itself as: isolated thrombocytopenia, risk of spontaneous hemorrhage and bleeding of varying severity. ITp is a hematological, orphan disease with an incidence of 1–4 cases per 100,000 population. In modern literature, primary and secondary immune thrombocytopenias are distinguished. primary immune thrombocytopenia is a diagnosis of exclusion. To verify it, a certain diagnostic search is required.Aim. To evaluate clinical characteristics and treatment efficacy in patients with a confirmed primary immune thrombocytopenia in the Moscow region.Materials and methods. This article presents the results of an analysis of more than 2,400 outpatient records of patients diagnosed with thrombocytopenia (for the period from 2010 to 2022). Of these, about 400 confirmed clinical cases of various ITp forms were included in the ITp registry of the Moscow Region. All patients live in the Moscow region, receive treatment and are observed at the Center for Orphan diseases of the M.f. vladimirskiy Moscow Regional Research Clinical Institute.Results. There are 415 patients with a verified diagnosis of ITp in the register of the Moscow Region Center for Orphan diseases of the M.f. vladimirskiy Moscow Regional Research Clinical Institute (71 % (n = 294) are female). In 69.8 % (n = 290) of patients at the time of disease manifestation, hemorrhagic syndrome was recorded. As a first-line therapy, 92.8 % (n = 385) of patients received corticosteroids (prednisolone, methylprednisolone, dexamethasone), in the second-line therapy, 82 % (n = 340) of patients were recommended therapy with thrombopoietin receptor agonists (romiplostim, eltrombopag). The options for third-line therapy in patients with ITp are rituximab monotherapy, splenectomy, and intravenous immunoglobulin. Splenectomy was performed in 3.37 % (n = 14) of patients.Conclusion. when evaluating this register, the highest efficiency of thrombopoietin receptor agonists (romiplostim, eltrombopag) is observed – 84.1 % of the objective response.

The aim of this research is to improve the quality of practical skills that are formed in future military doctors specialized in the organization of medical support. The work was performed in the department of the organization of medical support of military training center at the I.M. Sechenov First Moscow State Medical University.

Rationale: Most people infected with SARS-CoV-2 have asymptomatic or minor clinical manifestations and recover without any aggressive therapy. However, there are patient categories in need of specific treatment and those at high risk of severe disease. Control of viremia with antiviral therapy may not be the best therapeutic strategy, since, in addition to substantial toxicity, antiviral agents can suppress the production of antiviral antibodies and disintegrate adoptive immunity against SARS-CoV-2. Due to a high correlation between the symptoms severity in patients with COVID-19 and inflammation, anti-inflammatory corticosteroids have been proposed to treat the disease. However, clinical data do not support the systemic administration of corticosteroids for the treatment of patients with severe COVID-19. Such treatment may have a negative effect due to suppression of the adoptive immune system. In this regard, the development or use of already available of agents that modulate inflammation without compromising the adoptive immune response could be the most effective therapeutic strategy.Aim: To evaluate clinical efficacy and safety of the cell biotherapy technique, the extracorporeal photopheresis (ECP), in the treatment of patients with moderately severe new coronavirus disease COVID-19.Materials and methods: The study included four patients (three women and one man, age 42 to 60 years), with SARS-CoV-2 infection confirmed by gene amplification. All patients had CT-confirmed bilateral multisegmental viral pneumonia (grades > 2, i.e. with 25 to 60% involvement of the lungs). Prior to admission, all patients received antibiotics (azithromycin 500 mg daily and levo-floxacin / amoxicillin clavulanate 500 mg BID) and antipyretics for torpid fever of up to 38.5-39 °C. The outpatient treatment lasted for 8 to 14 days, with signs of progressive respiratory failure. In addition to the moderately severe and torpid course of viral pneumonia, three patients showed hematology test abnormalities, such as hypochromic anemia, leukopenia, leukopenia/lymphopenia, and moderate thrombocytopenia. Three patients had high C-reactive protein (CRP) levels. Inpatient treatment consisted of azithromycin 500 mg daily, levofloxacin 500 mg BID, hydroxychloroquine 200 mg BID, and low molecular weight heparin (enoxaparin 0.4 ml, 4000 anti-Xa IU, s.c. BID). Despite the treatment, the patients showed signs of progressive respiratory failure, with increasing dyspnea and gradual decrease in saturation from 96% to 92%. Isolation of peripheral blood mononuclear cells was done in an intermittent blood separator "Haemonetics MCS+” (USA), with subsequent cell irradiation with an extracorporeal blood irradiator (OKUFKE 320/400-600/650-01 "Yulia”, ZAO NPKF "METOM”, Russia). Ammifurin (ZAO "Pharmcenter VILAR”, Russia) was used as a photosensitizer. Three patients had two ECP sessions with an interval of 24 hours, and one patient had one ECP session.Results: In three patients who had received two ECP sessions, there was a regression of radiographic signs of viral pneumonia from CT2 to CT1 (less than 25% of lung tissue involvement) during the next four days (96 hours). In one patient, the follow-up CT showed resolving pneumonia with less than 5% involvement of the lungs. The patients (n = 3) with baseline high CRP levels showed their normalization at 4 days after two ECP sessions. At 24 hours after a single ECP session, leukocyte count and differential, as well as platelets were restored. In three patients, viral RNA tests within 2 to 4 days after ECP were negative. These results were associated with normalization of body temperature, no further progression of respiratory failure, and a reduction in hospital stay.Conclusion: The use of ECP in 4 patients with moderately severe SARS-CoV-2 infection has contributed to the rapid relief of clinical symptoms, resolution of the inflammation and restoration of respiratory abnormalities in all of them. These observations allow us to consider ECP as an effective and safe method of treatment for moderately severe COVID-19 and a promising adjuvant method in the high-risk patients in order to prevent an unfavorable disease outcome.

Objective: to study the efficacy and safety of the antitumor RVP program (lenalidomide, bortezomib, prednisone) as a first-line therapy in patients with multiple myeloma (MM). Materials and methods. A prospective study involved 39 patients with MM (15 women, 24 men), median age 61 years (30–76 years). All patients had Durie–Salmon stage III disease. According to the paraprotein isotype variant, 19 patients (48.7 %) had Gk myeloma, 8 (20.5 %) had Gλ, 4 (10.2 %) – Ak, 1 – Aλ, 1 – Dk, 1 – paraproteinemia Bens-Jones k and 1 – Bens-Jones λ, 2 – Dλ, and 2 patients – nonsecreting MM. The average level of plasma cells in the bone marrow was 31.7 % (0.8–80.0 %). In 14 (35.8 %) patients there were plasmacytomas of various localization (spine, cranial bones, clavicle, pleura). Nine (23.0 %) patients had renal failure, requiring the start of renal replacement therapy. The average Karnovsky index in the study group was 50 %. All patients received RVP therapy (lenalidomide 25 mg in 1–14 days, bortezomib 1.3 mg subcutaneously in 1, 4, 8, 11 days, prednisolone 60 mg/m2; the interval between courses was 42 days) as the first line therapy. Evaluation of therapy efficacy, characterized by overall survival, objective response rates (the number of complete, very good partial and partial remissions) was performed after 6 treatment courses. Results. The median follow-up was 15 months; the median of overall survival was not achieved. Objective antitumor response achieved in 29 (74.3 %) patients, including complete remissions in 3 (7.6 %), very good partial remissions – in 7 (17.9 %), partial remissions – in 19 (48.7 %) patients. In 2 out of 9 patients who received renal replacement therapy, independence from dialysis therapy was achieved. Cases of III–IV stage hematological and non-hematological toxicity in the study were not noted. Conclusion. The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated MM course.

Background: We have previously shown that the FAS, TNFR2, TRAIL, DR3, DR4/5 gene expression in patients with newly diagnosed chronic lymphoblastic leukemia (CLL) correlates with clinical manifestations of the disease: they are minimal in patients with high activity of the proapoptotic genes and low activity of the apoptosis-inhibiting genes, and advanced in patients with high expression of the anti-apoptotic and low expression of the pro-apoptotic genes.Aim: To compare the levels of expression of the external apoptosis pathway genes in patients with newly diagnosed CLL before and after chemotherapy with fludarabine, cyclophosphamide and rituximab (FCR), taking into account baseline clinical data and the response to treatment.Materials and methods: This prospective one-center cohort study included 23 patients with newly diagnosed CLL, who underwent clinical and diagnostic assessments and treatment from November 2014 to December 2017. Immunophenotyping of peripheral blood lymphocytes for CLL diagnosis was done by fourcolor flow cytometry. Expression of the external apoptosis pathway genes was assessed by realtime reverse transcriptase polymerase chain reaction. All patients were treated with a standard FCR regimen with subsequent maintenance treatment with rituximab.Results: There were more men (n = 16) than women among our 23 CLL patients. Median age was 64 years (range, from 47 to 77 years). Sixteen (16) patients had CLL Rai Grade I and II, and 7 patients had CLL Grades III and IV. For convenience of analysis, all patients were divided into two groups depending on the FAS gene expression. At baseline, the patients with high FAS expression had higher TNFR2 (p < 0.0015) and TRAIL (p < 0.0053) expression levels. Before FCR therapy, the patients with low FAS expression had higher lymphocyte counts (р = 0.0016) and lower erythrocyte counts (р = 0.0159). At baseline, there were more Grade I and II patients in the group with higher FAS expression (р = 0.0205). At day 3 after the end of a four day FCR cycle, there was an increase only of the FAS (p = 0.0025) and TRAIL (p = 0.0045) expression. After the completion of the first FCR cycle, lymphocyte counts in the patients with low FAS expression decreased earlier than those in the patients with high FAS expression (p = 0.0019). After six FCR cycles, complete or partial remission was obtained in 82% (19/23) of the patients. The patients with high FAS expression had higher complete remission rate (р = 0.026). No adverse events related to FCR were registered.Conclusion: The external apoptosis pathway genes are one of the key factors of the tumor progression in CLL. Our data on the effect of FCR therapy on the FAS and TRAIL gene expression make it possible to consider them as a target for this combination regimen and may become the rationale to develop new pharmaceutical molecules.

Background: Therapeutic efficiency in treatment of acute myeloid leukemia (AML) ranges from 20 to 45%. One of the causes of the latter is a drug resistance acquired by leukemic cells under the influence of treatment with antitumor medicines. More important cause is a development of the primary resistance of myeloid leukemic cells to induction of cellular death associated with elemental microenvironment within the bone marrow. Studying primary resistance is very important, and first of all, to prevent development of drug resistance of leukemic cells and, correspondingly, to increase the efficiency of medicamental therapy. Aim: To study the mechanisms of primary resistance of AML cells to induction of cellular death. Materials and methods: Human AML cells of THP-1 line and mononuclear cells of the bone marrow were used in the study of patients with diagnosed AML. Multicellular aggregates were formed during cell cultivating on the 1.5% agarose. To cut off intercellular adhesion, the cells were cultivated in the medium with methylcellulose (0.9%). The viability of the cells was assessed by reduction of Alamar Blue indicator. Results: Within multicellular aggregates, about 75±5% of THP-1 cells were resistant to the activity of recombinant protein izTRAIL, 70±5% – to etoposide, and 40±7% – to sorafenib. Cutting off intercellular contacts decreased the resistance to them. Within multicellular aggregates of primary mononuclear cells, 45±5% of cells were resistant to sorafenib, 57±4% – to etoposide, and all cells were resistant to izTRAIL. Cutting off intracellular adhesion reduced the resistance to sorafenib and etoposide but not to izTRAIL. Conclusion: In multicellular aggregates, AML cells of THP-1 line and mononuclear cells of the bone marrow showed increased resistance to activity of recombinant protein izTRAIL, etoposide, and sorafenib. Diminishing intracellular adhesion in the medium including methylcellulose decreases cellular resistance to cytotoxic agents.

49 patients aged 28 to 81 years old (median age of 55 years old) with relapsed or refractory multiple myeloma (MM) were enrolled in the study. The relapse was diagnosed in 25 (51 %) patients, the refractory disease was determined in 24 (49 %) patients (including primary refractory disease in 14 (28.6 %) patients). The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %). Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP). The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR) in 1 (2 %) patient; very good partial response (VGPR) in 4 (8 %) patients; partial response (PR) in 26 (53 %) patients; minimal response (MR) in 2 (4 %) patients; stable disease (SD) in 8 (16.3 %) patients, and progressive disease (PD) in 8 (16.3 %) patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 %) patients. The objective response rate, including MR, was seen in 33 (67.1 %) patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management.