Introduction. Life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) can have a significant influence on the short-term and long-term prognosis in recipients of hematopoietic stem cells (allo-HSCs).

Aim — to determine the life-threatening complications and the risk factors of their occurrence and to evaluate the short-term and long-term prognosis in critically ill allo-HSCs recipients.

Materials and methods. All patients over the age of 18 who underwent allo-HSCT from 01.01.2012 to 01.01.2022 were included in the retrospective study. Patients were divided into two groups: those who required intensive care unit (ICU) admission and those who did not require ICU admission. In the group of ICU admitted allo-HSCs recipients the reasons of ICU admission, timing of their occurrence and the results of life support were recorded. The risk factors of life-threatening complications occurrence and prognostic factors were analyzed.

Results. In total, 174 (26.7 %) of 652 allo-HSCs recipients required ICU admission. The risk factors of life-threatening complications were: allo-HSCT in patients with acute leukemia who did not achieve complete remission (hazard ratio (HR) = 2.10; 95 % confidence interval (95% CI): 1.28–3.44; p = 0.003), allo-HSCT without conditioning in patients with hematopoietic aplasia after chemotherapy (HR = 30.63; 95% CI: 8.787–107.04; p < 0.001), graft failure (HR = 2.51; 95% CI: 1.58–3.97; p < 0.001) and poor graft function (HR = 2.85; 95% CI: 1.6–5.05; p < 0.001), acute graft versus host disease (GVHD) (HR = 2.04; 95% CI: 1.459–2.85; p < 0.001). The main reasons of ICU admission were sepsis and/or septic shock (SS) (27.9 %), acute respiratory failure (23.9 %), neurological disorders (17.7 %). The type and periods of allo-HSCT influenced the timing and structure of critical illnesses. The ICU mortality rate after all ICU admissions and readmissions was 59.8 % with a maximum follow-up of 9 years. The risk factors of ICU mortality were the occurrence of critical conditions after +30 days of allo-HSCT, the need for mechanical ventilation and vasopressors. The overall survival (OS) rate of ICU admitted allo-HSCs recipients was 13.8 %. Sepsis and/or SS that occurred in the early phase after allo-HSCT were characterized by the most favorable long-term outcome (OS — 43.8 %) among all complications of the peritransplantation period. The OS of patients discharged from the ICU was worse than OS of patients who did not require ICU admission (34.6 % vs. 58.3 %; p = 0.0013). Conclusion. Transplant centers should have a specialized ICU because more than a quarter of allo-HSCT recipients experience life-threatening complications at different allo-HSCT periods. Sepsis and SS occurring in the early pre-engraftment phase had a more favorable prognosis than other life-threatening complications. The long-term outcomes in allo-HSCs recipients who survived critical illness are worse than in recipients who did not require ICU admission.

Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity.

Aim — to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML.

Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study; average age — 32; stage > I — in 60 %; extramediastinal lesions — in 14.7 %; bulky disease — in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed; ctDNA was determined to assess the completeness of remission.

Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy; 2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy; 2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission; 7 (44 %) retained pathological activity (D4–5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3–6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission.

Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose shortpulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the “PML-19” program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.

Introduction. Given the possibility of preserving molecular remission in 40–60 % of patients with chronic myeloid leukemia (CML) with a stable deep molecular response (MR) after discontinuation of tyrosine kinase inhibitors (TKI), it is important to determine the number of candidates for observation in a treatment-free remission (TFR) and terms of treatment cancellation.

Aim — to evaluate the probability of stable deep MR and the rate of patients who meet the criteria for TFR observation in the Russian part of the international multicenter prospective population study EUTOS PBS (European Treatment and Outcome Study — Population-Based Study).

Materials and methods. Registration of all CML cases in the EUTOS PBS was conducted in 6 regions of Russia from September 2009 to December 2012. The main inclusion criterion was the diagnosis of CML confirmed by cytogenetic or molecular study in patients aged over 18 years. In total, 197 CML patients were included: 181 (92 %) with chronic phase (CP) CML, 14 (7 %) with accelerated phase (AP) and 2 (1 %) with blast crisis (BC) at diagnosis. Data on therapy and results was updated annually.

Results. Deep MR (at least MR4 or BCR::ABL1 level less than 0.01 % IS) was achieved in 104 (54 %) of 192 patients receiving TKI therapy, with a median observation period of 7 years (range from 3 months to 10 years). The probability of a deep MR after 5 years of treatment was 48 % (95 % confidence interval (95% CI): 40–55 %) in patients with CP. The cumulative incidence of a stable deep MR with duration of more than 2 years in CML CP patients was 16 % (95% CI: 11–22 %) after 5 years of therapy, 29 % (95% CI: 22–37 %) after 7 years of therapy and 50 % (95% CI: 38–60 %) after 9 years of therapy. The cumulative incidence of a stable deep MR was significantly higher in those patients who had achieved a deep MR at 36 months of therapy compared to patients with only MMR: 40 % (95% CI: 28–53 %) vs. 3 % (95% CI: 0–13 %) at 5 year of therapy; 66 % (95% CI: 52–77 %) vs. 15 % (95% CI: 5–30 %) at 7 year and 89 % (95% CI: 64–97 %) vs. 48 % (95% CI: 25–67 %) at 9 year (p < 0.0001) in patients without MMR by 36 months. No patients without MMR at 36 months of therapy subsequently gained a stable deep MR. Fifty four patients met the TKI discontinuation criteria for transition into TFR phase: CP CML with a typical BCR::ABL1 p210 transcript, TKI therapy for more than 3 years and a stable deep MR for over 2 years. The rate of possible candidates for cancellation of therapy was 28 % of all 192 patients who received TKI in the study or 31 % in terms of patients with CP CML. Predominantly, patients with low-risk by Sokal or ELTS score were among the potential TFR candidates 26 (48 %) and 33 (61 %), respectively. No patients with long-term resistance to therapy were the TFR candidates.

Conclusion. In the Russian portion of the prospective observational multicenter study EUTOS PBS, it was found that with a median duration of TKI therapy of 7 years, about a third of patients with CP CML may be candidates for the controlled therapy discontinuation. If half of these patients remain in molecular remission, up to 15 % of the initial number of patients will be able to continue observation in the TFR. Achievement of MMR and deep MR at 36 months of therapy is associated with a significantly greater likelihood of meeting the criteria for follow-up in the TFR phase in the future.

Introduction. The hemostasis system plays a key role in the pathogenesis of cardiovascular diseases.

Aim — to evaluate changes in quantitative and qualitative characteristics of ADAMTS13 metalloprotease and von Willebrand factor an tigen (vWF:Ag) in patients with acute myocardial in farction (AMI) and is chemic stroke (IS).

Patients and methods. The study in cluded 110 patients aged 42–95 years (median age — 64 years), of which: 65 patients with AMI aged 42–81 years (median age — 56 years) who had coronary artery thrombosis during an giography, as well as 45 patients with IS aged 40–95 years (median age — 70 years) with diagnosed cerebral artery thrombosis. All patients were tested for ADAMTS13 an tigen, ADAMTS13 activity, an tibodies to ADAMTS13 and vWF:Ag. Blood samples were obtained during an giography (arterial and venous blood) and 24 and 120 hours after an giography (venous blood).

Results. In the group of patients with AMI, an in crease in the values of the vWF:Ag in dicator was revealed, which went beyond the upper limit of the reference in terval. In patients with IS, at the beginning of the study, this in dicator was within the reference in terval and was statistically significantly lower compared to patients with AMI but in creased after 24 hours and peaked at 120 hours. When an alyzing changes in the ADAMTS13:Ag in dicator, it was found that it was statistically significantly higher at all points of the study in the group of patients with AMI, compared with the group of patients with IS, however, the values of this in dicator did not go beyond the reference in terval in patients of both groups. At the same time, the ADAMTS13:AC in dex at all points of the study was statistically significantly higher in patients with IS, compared with the group of patients with AMI, and the ADAMTS13:AB in dex. On the contrary, in the group of AMI patients, this in dicator was statistically significantly higher in all points of the study when compared with that for the group of patients with IS.

Conclusion. The study of two pathogenetic models of thrombosis demonstrated the absence of a relationship between the vWF:Ag in dex and the quantitative or qualitative characteristics of the ADAMTS13 metalloprotease. At the same time, an in crease in ADAMTS13:AB in AMI can be considered as the reason for the decrease in ADAMTS13:AC in these patients.

Introduction. Haplotype JAK2 46/1 is associated with more frequent development of Ph-negative myeloproliferative neoplasms (MPN) and with an increased detection rate of the JAK2 V617F mutation. At the same time, the molecular mechanisms of such associations remain unclear. Previously, there were no studies of regional, age and gender aspects of the predictive value of carriage of the 46/1 JAK2 haplotype, which could assess this relationship in some observations.

Aim — to analyze the degree of association between 46/1 haplotype and the V617F mutation of the JAK2 gene depending on the sex, age, and place of residence of patients examined for suspected MPN.

Methods. The study included 949 DNA samples from patients with suspected MPN. Samples of 150 volunteers and blood donors were included in the control group. Haplotype 46/1 (rs10974944), V617F mutation in the JAK2 gene, mutations in the CALR gene (type 1: c.1092_1143del; L367fs*46, COSV57116546; type 2: c.1154_1155insTTGTC; K385fs*47, COSV57116551) and in the MPL gene (W515K, W515L) were determined for all samples using real-time polymerase chain reaction (PCR-RT).

Results. The 46/1 JAK2 haplotype were shown to be associated with a clinically significant level (> 2 %) of the allelic burden of the JAK2 V617F mutation. The odds ratio of the risk of developing a V617F positive MPN when carrying this haplotype variant did not depend on the main place of residence of the patients and was found to be most pronounced in men under 50 years of age. The odds ratio of the risk did not depend on the age of the examined women.

Conclusion. The association of 46/1 haplotype with the presence of other drivers of MPN mutations in the CALR or MPL genes was also statistically significant, which confirms the hypothesis of “favorable soil” rather than “hypermutability” of the JAK2 gene.

Introduction. Ensuring a sustainable supply of safe donor blood is crucial for strategic issues and challenges. The evaluation of donor characteristics as well as the volume of components harvested and issued to medical organizations in the Russian Federation is a topical task for the national blood service.

Aim — to analyze the performance indicators of the national blood service for the procurement and provision of donated blood and its components to medical organizations from 2016–2020.

Methods. Data on over 6.5 million donors who donated blood in Russia during 2016–2020 were analyzed. Data were obtained from Blood Service report form No. 39 “Blood products and derivatives”. Descriptive statistics were used during analysis.

Results. A decrease of the number of blood donors per thousand population was shown (from 9.68 to 8.26, р < 0.0001). There was a decrease of the number of first-time donors and of the number of repeat donors (by 23 and 9.3 %, respectively) within studied period. Regular donor quantum increased from 71 to 76 %. The share of volunteer blood donors from 2016 to 2020 throughout the Russian Federation remained stable and amounted to 97.7–98.0 %. The total number of donations decreased by 6.0 % due to a significant decrease in the number of donations of automatic apheresis plasma (from 507,396 in 2016 to 388,742 in 2020, p < 0.001), at the same time, a significant increase in the number of donations platelets was noted (from 83,285 donations in 2016 to 126,574 in 2020, p < 0.001). During the follow-up period, there was an increase from 2.0 in 2016 to 2.21 in 2020 (10 %) in the average number of donations of blood components made by donors per year. Despite the decrease in the total number of donations in the analyzed period, the volume of blood components transferred for clinical use increased. The largest increase in blood components transferred at the request of medical organizations was noted for the concentrate of donor platelets (from 702,732 units in 2016 to 1,072,830 in 2020, by 34.5 %) and erythrocyte- containing blood components (from 491,791 liters in 2016 to 555,909 liters in 2020, by 13.5 %). A general trend was noted both towards a decrease in the frequency of detection of markers of bloodborne infections (from 16.8 to 7.7 %), and in individual infections. When analyzing the frequency of detection of infection markers, a significant difference was obtained in the group of newly registered and repeated donors (50,114 and 25,814, р < 0,001).

Conclusion. The decrease of the number of cases of detection of infection markers and the redistribution of blood collection in accordance with the changing demands of medical organizations demonstrates a targeted strategy for improving the safety of transfusions, improving the quality of recruiting activities, and improving the principles of lean production of blood components.

Introduction. Sepsis is one of the main causes of high mortality in oncohematological patients. Sepsis is diagnosed using different scoring scales, but the accuracy of the diagnosis varies.

Aim — to determine the effectiveness of SIRS, qSOFA and MEWS scales for the diagnosis of sepsis in oncohematological patients.

Materials and methods. Study participants included 202 patients hospitalized in the intensive care unit with infectious complications — 112 (55 %) male, 90 (45 %) female. The median age was 57 years. The estimated predictors were the criteria of SIRS, qSOFA and MEWS scales and other significant indicators. The Boruta method was employed to select the predictors. A multiple binomial logistic regression model was used to determine the prognostic value of the predictors. The probability of sepsis was calculated based on the regression equation. The correlation between sepsis probability and the prognostic scales was assessed using correlation analysis (Kendall rank correlation coefficient).

Results. Diagnoses were confirmed by scales in 95 of 202 (47 %) patients: SIRS — in 77 (81 %), qSOFA — in 31 (33 %), MEWS — in 65 (68 %). Of the 19 predictors initially included in the study, the final logistic regression model included 6: respiratory rate, heart rate, impaired urine output, systolic blood pressure, body temperature, and Glasgow coma scale level, which matched MEWS criteria. The median probability of sepsis was 0.38 (0.079–0.921). The results of the calculated probability of sepsis, according to the logistic regression model, correlated most closely with the score on the MEWS scale, to a lesser extent — with that on SIRS and qSOFA.

Conclusion. The MEWS scale is a more suitable tool for the diagnosis of sepsis than SIRS and sofa in oncohematological patients.

Introduction. Endothelial cells and platelets are actively involved in pathogenetic processes in sepsis — an unregulated reaction of the host organism in response to infection, leading, on the one hand, to the development of prothrombotic, and on the other hand, to hemorrhagic readiness.

Aim — to summarize the current information on the mechanisms of intercellular interaction between endotheliocytes and platelets in sepsis.

Main findings. The development of multiple organ failure, which increases the likelihood of an unfavorable outcome of sepsis, is partly due to endothelial dysfunction, as well as the involvement of platelets in the pathogenetic process. Under physiological conditions, an anatomically and functionally intact endothelium is important to prevent microvascular thrombosis. Although platelets are most associated with hemostasis, they perform many other functions, including participation in inflammatory processes through complement activation, interaction with leukocytes and monocytes, participation in host defense against infection, and regulation of vascular tone. There is also abundant evidence that suggests that the processes regulating hemostasis evolved as a component of the inflammatory response to infection. Many of these interaction points occur on the surface of endothelial cells, linking these two cell types, endotheliocytes and platelets, in initiating and regulating blood clotting and inflammation. Various mechanisms may contribute to direct and indirect platelet activation in sepsis, including pathogen-induced platelet activation, pathogen- and inflammation-induced endothelial and leukocyte activation, and complement-mediated platelet activation.

Introduction. Von Willebrand factor (vWF) is a large plasma glycoprotein that plays a major role in hemostasis. The vWF plasma concentration is not included in modern stoke risk stratification scales in patients with atrial fibrillation (AF).

Aim — to evaluate the possibility of usage of vWF plasma concentration in stroke risk stratification in patients with atrial fibrillation.

General findings. vWF is an important predictor of stroke development in patients with AF based on the results of the conducted meta-analysis that included 12 studies and 7449 patients with AF. Determining the concentration of vWF in patients with low risk of stroke development or in those patients with a single non-sex CHA2DS2-VASc score risk factor may be useful in deciding whether to prescribe anticoagulant therapy.

Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disease of the blood system characterized by intravascular hemolysis, bone marrow dysfunction and an increased risk of thrombotic and organ complications.

Aim — to provide relevant clinical recommendations for the provision of medical care to adults and children with PNH.

Basic information. Experts from the National Hematological Society association which is focused on the promotion of hematology, transfusiology and bone marrow transplantation along with experts from the public organization, National Society of Pediatric Hematologists and Oncologists, have developed current clinical recommendations for providing medical care to adults and children with PNH. The recommendations address in detail the issues of etiology, pathogenesis, epidemiology, and clinical manifestations of the disease. Special attention is paid to the diagnosis, differential diagnosis, and treatment of PNH based on the principles of evidence.

Introduction. The tactics of therapy for elderly comorbid patients with mantle cell lymphoma with unfavorable prognosis factors (complex karyotype, 17p13 deletion, mutations in the TP53 gene) have not been developed. The use of intensive chemotherapy regimens and transplantation of allogeneic hematopoietic stem cells (allo-HSCT) is impossible due to severe comorbidity in elderly patients. A rational approach is the use of a combination of ibrutinib and venetoclax. As an alternative to allo-HSCT, a new option for elderly patients with poor prognostic factors is Chimeric Antigen Receptor T-cell therapy (CAR-T) cell therapy.

Aim — to present the experience of using ibrutinib and venetoclax with CAR-T-cell therapy in the first line of treatment in an elderly patient with MCL with a mutation in the TP53 gene and hyperleukocytosis.

Main findings. Patient M., 68 years old. The examination revealed hyperleukocytosis 978 × 10⁹/L, anemia (55 g/L), thrombocytopenia (30 × 10⁹/L), and splenomegaly 250 × 180 mm. According to the results of laboratory studies, the diagnosis of lymphoma from mantle cells with a complex karyotype, deletion 17p13, 13q14 and mutation p.R248W in exon 7 of the TP53 gene (VAF = 26 %) was verified. For cytoreductive purposes, two sessions of leukocytapheresis and prephase with cyclophosphamide (200 mg/m²) and dexamethasone (10 mg/m²) were performed. From day 3, therapy with ibrutinib 420 mg/day and venetoclax 100 mg/day was started. After 2 days, the leukocytes were 0.7 × 10⁹/L, and the size of the spleen decreased, as a result of which the development of tumor lysis syndrome was noted. As a result of intensive therapy, the patient’s condition stabilized, which allowed him to resume treatment. After 7 days, the number of leukocytes was 2.5 × 10⁹/L, neutrophils — 70 %, platelets — 90 × 10⁹/L, hemoglobin — 95 g/L. According to immunophenotyping, the population of B-lymphocytes was 4 %. According to NGS data, the allelic load of the mutation in the TP53 gene is 0.8 %. The patient underwent anti-CD19 CAR-T-cell therapy and achieved complete remission. Three months after therapy, MRD remains-negative remission and the persistence of CAR-T cells is determined.