Introduction. The role of the cytokine environment and immune deregulation in the pathogenesis of mycosis fungoides is unquestionable. Despite the fact that one of the methods of therapy for the early stages of mycosis fungoides is phototherapy (PUVA, UVB-311 nm), the effect of ultraviolet radiation on the lymphoproliferative substrate and pathogenetic links in mycosis fungoides has not been fully studied.

   Aim: to evaluate the effect of NB-UVB and PUVA therapy on the dynamics of cytokine mRNA expression in the affected skin of patients with mycosis fungoides.

   Material and Methods. A comparative non-randomized study of the cytokine mRNA expression dynamics in the affected skin and of the effectiveness of phototherapy was carried out in 28 patients with early stage of mycosis fungoides. The IL4, IL17A, IL17F, and IL22 mRNA expression was determined relative to the endogenous control GAPDH using the real-time reverse transcription PCR (RT-PCR). Evaluation of the effectiveness of NB-UVB and PUVA therapy was carried out using a BSA score (skin lesion area) and a modified severity-weighted assessment tool (mSWAT) score.

   Results. The study included 28 patients with early stages (IA–IIA) of mycosis fungoides; 9 patients received NB-UVB and 19 received PUVA therapy. 3.71-fold decrease in mSWAT (p < 0.008), and 3-fold decrease in BSA scores (p < 0.013) were observed in the NB-UVB-treated group. In the PUVA-treated group 3.47- and 2.19-fold lower scores of mSWAT (p < 0.001) and BSA (p < 0.001) were found. There were no significant differences in the expression of the studied cytokines in the NB-UVB-treated group; however, a significant 19 and 72 % increase in IL17F (p = 0.003) and IL22 (p = 0.021) was revealed after
PUVA therapy. Correlation analysis has shown a weak correlation between IL4 and IL17A (r = 0.43, p < 0.027), and IL17F (r = 0.43, p < 0.028) before the treatment. Under the influence of phototherapy, the formation of a cytokine network in the affected skin was observed: there were positive associations between IL4 and IL17A (r = 0.73, p < 0.001), IL17F (r = 0.7, p < 0.001) and IL22 (r = 0.43, p < 0.024); IL17A and IL17F (r = 0.78, p < 0.001); IL22 and IL17A (r = 0.63, p < 0.001) and IL17F (r = 0.66, p < 0.001). In the PUVA-treated group a high negative correlation between IL17A and mSWAT (r = -0.79415, p =
0.010586), BSA (r = -0.75432, p = 0.018849) were found.

   Conclusion: The positive correlations between IL4, IL17A, IL17F and IL22 in the affected skin of patients with mycosis fungoides may underlie the positive effect of phototherapy.

   Introduction. When establishing a diagnosis of thrombotic thrombocytopenic purpura (TTP) for the first time, other diseases occurring with thrombocytopenia may be misdiagnosed.

   Aim: to analyze diagnostic difficulties and errors of TTP.

   Materials and methods. In total, 54 patients (44 women and 10 men) aged 18 to 83 years (median 33 years), who were diagnosed TTP from 2019 to 2023, were included in the study. Anamnesis, baseline hemoglobin, platelets, erythrocytes, lactate dehydrogenase and bilirubin serum concentrations, pre-established diagnoses, treatment, and outcomes were analyzed.

   Results. Initially TTP was suspected only in 19 (35 %) patients. In 12 out of 54 patients immune thrombocytopenia (ITP) was initially misdiagnosed. Fisher-Evans syndrome was initially suspected in 3 patients. In sporadic cases, myelodysplastic syndrome, systemic lupus erythematosus / antiphospholipid syndrome, autoimmune hemolytic anemia were initially suspected. Among 15 women with associated with pregnancy TTP in 8 (53.3 %), HELLP syndrome was initially misdiagnosed. In total, 12 (22.2 %) of 54 TTP patients died. In 11/12 non-survival patients, TTP treatment was never started, because the doctors were waiting for the ADAMTS13 test results. A case report of Sequential Immune Thrombocytopenia (ITP) and TTP in the same Patient is described.

   Conclusion. When thrombocytopenia is combined with hemolysis and in the absence of multiple organ pathology, it is difficult to differentiate ITP and TTP without examining the plasma activity of ADAMTS113. With a combination of ITP and TTP in the same patient, the study of ADAMTS13 plasma activity makes it possible to identify the leading mechanism of thrombocytopenia and choose treatment tactics.

Introduction. The blood coagulation system plays a significant role in the pathogenesis of sepsis.

   Aim: to evaluate changes in the quantitative and qualitative characteristics of von Willebrand factor (vWF), ADAMTS13 metalloprotease and P-selectin in patients with sepsis, comparing them with those in patients with idiopathic thrombocytopenic purpura and in healthy individuals.

   Materials and methods. The study included 56 patients who received inpatient treatment due to the development of sepsis of various etiologies, 12 patients with idiopathic thrombocytopenic purpura (ITP) and 50 healthy volunteers. In a venous blood sample, the following studies were performed: vWF antigen (vWF:Ag), GPIb-binding ability of vWF (vWF:GPIb), binding ability of vWF to type I collagen (vWF:CBAI), binding ability of vWF to type III collagen I (vWF:CBAIII), P-selectin, ADAMTS13 antigen (ADAMTS13:Ag), ADAMTS13 activity (ADAMTS13:AC) and antibodies to ADAMTS13 (ADAMTS13:AB).

   Results. The median values of vWF:Ag, vWF:GPIb, vWF:CBAI, and vWF:CBAIII were significantly higher in patients with sepsis compared to healthy individuals and patients with ITP. The median P-selectin in patients with sepsis with thrombocytopenia 1213 ng/mL [1104–1302] was statistically significantly higher than in healthy individuals 74.5 ng/mL [65.0–84.5] (p = 0.0001), and with patients with ITP 389.0 ng/ml [276.2–589.2] (p = 0.0001). Median ADAMTS13:Ag in patients with sepsis with thrombocytopenia < 100×109/l 0.49 U/ml [0.44–0.71] and in patients with ITP 0.67 U/ml [0.62–0.76] were significantly lower compared with healthy individuals 0.97 U/ml [0.84–1.08] (p = 0.001 and p = 0.034, respectively), but the median ADAMTS13:Ag in patients with sepsis with thrombocytopenia was statistically significantly lower than in patients with ITP (p = 0.038). In 19.6 % of cases in patients with sepsis, the ADAMTS13:AB index was higher than 10.0 U/ml (19.6 U/ml [12.1–26.7]), while the median P-selectin indicator in this group of patients was significantly higher when compared with a group of patients with sepsis with an ADAMTS13:AB score of less than 10.00 U/mL (3.04 [2.11–3.94]): 1342 ng/mL
[1271–1374] vs. 1130 ng/mL [1087–1271], p = 0.003, respectively.

   Conclusion. Activation of endothelial cells may underlie the increase in quantitative and qualitative indicators of vWF. Meanwhile, the effect of the adhesive characteristics of vWF (vWF:GPIb, vWF:CBAI and vWF:CBAIII) on the number of platelets in the blood of patients with sepsis was not revealed. Adhesion of vWF to the endothelium through interaction with P-selectin through the platelet GPIb receptor can promote the transition of vWF into a conformational-active state and lead to a decrease in the concentration of ADAMTS13 in the circulation.

   Introduction. The follicular lymphoma (FL) is the most common indolent lymphatic tumor with high sensitivity to immunochemotherapy un most cases. Although overall survival (OS) is generally long, the disease is characterized by multiple relapses. High-dose chemotherapy (HDCT) with transplantation of autologous hematopoietic stem cells (auto-HSCT) is used for recurrent FL.

   Aim: to evaluate the efficacy and safety of HDCT with aHSCT in the first line of FL therapy; identify risk factors for disease progression and refractoriness.

   Material and methods. A prospective single-center study (conducted from May 2015 to January 2023) included 35 patients aged 18–65 years (median 43) with PL 1–3A grade t(14;18)+ with stages III–IV or stage II with bulky, having at least one criterion for the need to start therapy (according to GELF). Patients were treated according to the FL-2015 protocol: 4 R-CHOP, 2 R-DHAP and BeEAM with auto-HSCT. The primary endpoint was the rate of overall response (OR) and/or complete remission (CR) at the end of chemotherapy. Secondary end points were 3-year survival rates: OS, relapse-free survival (RFS), progression-free survival (PFS), and event-free survival (EFS). Minimal residual disease (MRD) in blood and/or bone marrow was assessed by PCR based on immunoglobulin heavy chain (IGH) gene rearrangements and/or BCL2::IGH rearrangements. Statistical analysis (by intent to treat) was performed on January 12, 2023.

   Results. 86 % of patients had stage IV tumor and 79 % had 3–5 FLIPI factors. After the end of treatment, OR and PR were 90 % and 90 %, the incidence of POD24 was 3 %. After the end of induction (4 courses of R-CHOP), MRD-negativity was achieved in 77 % and 53 % of patients as determined by PCR-IGH and BCL2::IGH. After the full completion of the FL-2015 protocol, MRD was not detected in 96 % of patients (according to PCR-IGH). Three-year overall survival, disease-free survival, progression-free survival and event-free survival were respectively: 90 %, 90 %, 95 % and 85 % (with the same standard
error of 9 %) at a median follow-up (by inverse Kaplan-Meier estimate) of 19 months (range: from 1 to 91 months) There were no deaths due to early toxicity within 100 days of auto-HSCT. Prognostically unfavorable independent statistically significant (р < 0.01; Wald test; hazard ratio > 1) predictors of progression and refractoriness according to the results of multivariate analysis using the Fine-Grey competing risk model (р = 0.052 for the model) were: bone marrow disease, ECOG high risk, patient age > 50 years, stage 4 disease, elevated serum lactate dehydrogenase and B-symptoms.

   Conclusion. The use of HDCT with auto-HSCT in the first line in patients with FL is highly effective and can significantly reduce the incidence of POD24 and early mortality from the tumor. The study is ongoing.

  Introduction. Ph-negative myeloproliferative neoplasms (MPN) are chronic clonal disorders characterized by the proliferation of mature cells from one or more myeloid cell lines. These disorders include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The incidence of classical Ph-negative MPN varies significantly throughout the world. These differences may be due to geographical or population features, as well as due to differences in methods of diagnosis and recording.

   Aim: to determine incidence of Ph-negative MPN in Belarus.

   Materials and methods. Data on all cases of newly diagnosed Ph-negative MPNs (PV, ET and PMF) for 2014-2018 were collected from central regional medical institutions with a hematology specialization. Population epidemiological analysis of incidence was carried out by determining crude incidence rates per 100 000 population per year with distribution by gender
and age groups at diagnosis, age-standardized rates, as well as average annual percent change.

   Results. The overall annual standardized incidence rate of classical Ph-negative MPN in Belarus was 1.96 (1.86–2.07), PV — 0.93 (0.86–1.01), ET — 0.63 (0.57–0.70) and PMF — 0.40 (0.36–0.45) per 100 000 population per year, respectively. The overall crude incidence rate was 3.26 (3.10–3.43) per 100 000 population. The crude incidence rates increased steadily with the increase in age of patients with a peak value of 12.78 (10.97–14.81) in the age group of 70–74 years. No significant changes were revealed in the overall incidence of the MPN and for each of the studied diseases separately during the study period.

   Conclusion. For the first time the nationwide features of incidence of the Ph-negative MPN in Belarus were estimated, which made it possible to provide substantial information for public health management. The incidence of MPN in Belarus is generally comparable to the levels determined in the analysis of the populations of other countries.

   Introduction: A frequent clinical manifestation of Ph-negative myeloproliferative neoplasms (MPN) is the development of thrombosis. To identify the state of hypercoagulation it is relevant and promising to introduce global tests for evaluating the hemostasis — the thrombin generation test (TGT) and thromboelastography (TEG).

   Aim: to evaluate the parameters of thrombin generation and thromboelastography in patients with Ph-negative MPN.

   Material and methods. In total, 62 patients with MNP were included in the study: 27 with polycythemia vera (PV), 14 with essential thrombocythemia (ET) and 21 with primary myelofibrosis (PMF). The control group included 55 practically healthy individuals, comparable in gender and age (19 people in the study of TEG, 36 people in the study of TGT). The TEG was performed using a “TEG 5000” thromboelastograph. TGT was measured with Calibrated Automated Thrombinography.

   Results: Ly30 and Ly60 in TEG in patients were significantly lower (0.35 (0.20–0.48), 0.00 (0.00–0.40) and 0.00 (0.00 — 0.43) and 3.15 (2.45–3.60), 1.25 (0.10–3.58) and 0.60 (0.00–3.05) respectively), than in the control (1.60 (1.05–2.75) and 6.20 (4.15–8.30), respectively), which indicates the ineffectiveness of fibrinolysis. The values of MA and G in patients with ET and PV significantly exceeded the control (69.15 (67.98–70.78) mm and 65.20 (59.65–63.83) mm versus 62.00 (57.75–6.75) mm and 11.20 (10.60–12.15) din/cm² and 9.40 (7.40–11.60) din/cm² versus 8.20 (6.85–8.75) din/cm², respectively. The most pronounced change in sensitivity to TM was observed in patients with ET (27.94 (17.35–43.58) % and 13.29 (-3.48–23.60) %, respectively; p < 0.05). A significant decrease in ETP was observed in patients with PV and PMF.

   Conclusion. The study of hemostasis in patients with MPN using TEG and TGT revealed the presence of multidirectional changes associated with the disease. The TEG showed that an increase in the time required for the onset of fibrin formation is combined with increased clot strength and inhibited fibrinolysis, which are risk factors for the development of thromboembolic complications. The study of TGT determined a decrease in the quantitative characteristics of thrombin generation and at the same time the failure of the anticoagulant system of protein C, leading to the development of hypercoagulation.

   Introduction. Testing for antibodies to the causative agent COVID-19 is not mandatory for donor blood or its components. It is unknown whether transfusion of plasma-containing blood components from seropositive donors is a safe procedure especially for immunocompromised hematological patients.

   Aim. To assess the frequency of adverse reactions and complications in hematological patients after transfusions of plasma-derived blood products harvested from anti-SARS-CoV-2 positive and negative donors.

   Material and Methods. 9152 transfusions of components harvested from anti-SARS-CoV-2 positive and negative donors were carried out from April 29, 2020 to January 21, 2022 at the NMRC for Hematology. Post-transfusion reactions and complications were analyzed in 576 hematological patients. 2059 plasma units, 327 cryosupernatant plasma units and 6766 cryoprecipitate doses were assessed. The occurrence of adverse reactions (hyperthermia) and complications within two hours after transfusion were evaluated.

   Results. Among 9152 blood units, anti-SARS-CoV-2 were detected in 2660 (29 %) cases and 6492 (71 %) were antibodies free. The analysis of adverse reactions and complications showed no significant differences in the incidence of adverse reactions in recipients after anti-SARS-CoV-2 positive and negative blood unit transfusions.

   Conclusion. There were no significant differences in the number of post-transfusion reactions when using donor blood components (fresh frozen plasma, cryosupernatant plasma, cryoprecipitate) obtained from donors in whose blood antibodies to SARS-CoV-2 were detected or not detected. Plasma-derived blood products from seropositive donors with a high degree of probability can be used to correct the plasma hemostasis path in hematological patients along with components prepared from seronegative donors.

   Introduction. One of the complications of the new coronavirus infection (COVID-19) is the development of venous thromboembolic complications. In this regard, changes in the hemostasis system that persist in the process of recovery in patients who have had a mild form of the disease are of interest.
Aim. To evaluate plasma hemostasis in patients after mild coronavirus infection

   Materials and methods. 39 patients after mild coronavirus infection were examined. The following parameters were assessed: APTT, PT, fibrinogen, factor VIII, von Willebrand factor, D-dimer, proteins C and S, and thrombin generation.

   Results. In patients who underwent COVID-19, in comparison with healthy individuals, an increase in the plasma concentration of fibrinogen, von Willebrand factor antigen, and D-dimer was detected. Furthermore, increased activity of antithrombin III, decreased sensitivity to thrombomodulin, and an increase in the coagulation index were detected.

   Conclusion. Patients who have undergone COVID-19 are characterized by a procoagulant orientation of changes in plasma hemostasis that persist up to 3 months after the disease. It is necessary to take into account the state of the hemostasis system even in patients who have undergone COVID-19 in mild form.

   Introduction. Relapses of primary mediastinal large B-cell lymphoma (PMBСL) with involvement of the central nervous system (CNS) are usually incurable. Therapy tactics in patients with PMBCL with relapse in the CNS have not been defined.

   Aim: to present clinical observations of the treatment of relapses of PMBCL with CNS involvement using the “R-PML-CNS-2022” protocol.

   Main findings. Two clinical observations of patients with relapses of PMBCL with involvement of the CNS are presented. In both cases, the “R-PML—CNS-2022” protocol was used as a second-line treatment, and a complete remission of the disease was achieved. In the first case, within 6 months after auto-HCT, maintenance therapy with pembrolizumab was performed. Complete remission of the disease continues for 15 months. In the second observation, maintenance therapy with pembrolizumab was also started, however, due to the development of autoimmune complications after 2 cycles, treatment was discontinued. Complete remission of the disease continues for 13 months.

   Conclusion. The development of a new strategy for the treatment of relapses of PMLCL with CNS lesion according to the “R-PML—CNS-2022” protocol is a potentially curative approach in this group of patients.

   Introduction: May — Hegglin anomaly is an autosomal dominant mutation in the MYH9 gene that disrupts the dynamics of the cytoskeleton in megakaryocytes. Megakaryocyte dysfunction entails a violation of thrombocytopoiesis, which is manifested by macrothrombocytopenia, sometimes associated with bleeding.

   Aim: to study the structure and function of platelets in the family members with documented May — Hegglin anomaly.

   Patients and methods. The proband, her sister and their mother who all had a heterozygous mutation R1933X in the MYH9 gene were examined. The examination included complete blood count, peripheral blood microscopy, platelet flow cytometry, blood clot contraction kinetics, scanning and transmission electron microscopy of platelets. The control group included
10 healthy donors.

   Results. In the proband and her sister the degree of contraction of blood clots was reduced. Unstimulated platelets displayed overexpression of P-selectin and active αIIbβ3 integrin. After TRAP-induced stimulation the proportion of platelets expressing P-selectin in the patients was below normal, indicating partial platelet refractoriness. Electron microscopy of the unstimulated platelets revealed macrothrombocytosis and multiple filopodia, as well as enlargement of the open canalicular system.

   Conclusion. The May — Hegglin anomaly caused by a heterozygous mutation R1933X in the MYH9 gene is accompanied by thrombocytopenia associated with structural and functional platelet defects. Partial platelet refractoriness and contractile dysfunction can impair the retraction of hemostatic clots, predisposing patients with MYH9-related disorders to bleeding.