Introduction. Relapse of acute myeloid leukemia (AML) develops in children who received intensive chemotherapy and achieved the first complete remission (CR1). Only intensive anti-relapse chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HSCT) may lead to cure.

Aim — to present the results of treatment of children with AML who relapsed after completion of treatment or while on therapy according to the AML-MM-2006 protocol.

Materials and methods. The study included children with AML who relapsed after completion of treatment of the first-line therapy according to the AML-MM-2006 protocol. During the follow-up period (median — 4.6 years), 68 relapses were registered among 187 patients who reached CR1 (early — 36, late — 26; with a change of phenotype to ALL-6). The cumulative probability of relapse was 40 %. Four (6 %) patients with relapsed AML initially belonged to the group of standard, 33 (54 %) — of intermediate risk of relapse of AML and 25 (40 %) — to the group of high risk. Eleven (18 %) were patients with “CBF-leukemia”, 19 (31 %) — with rearrangements of the 11q23 (KMT2A gene). Fludarabine, high doses of cytarabine and idarubicin in 33 (80 %) or mitoxantrone in 8 (20 %) patients were used to induce the second complete remission (CR2) in 41 patients (66 %).

Results. Out of 53 patients who received chemotherapy as a second induction therapy, CR2 was achieved in 30 patients (57 %) (in 9 — with early, in 21 — with late relapse) after chemotherapy courses; 2 patients died within 30 days of the start of CT; 21 patients were refractory to chemotherapy. HSCT after relapse was performed in 51 patients, mainly from a haploidentical donor. Twenty-five patients underwent HSCT in CR2, 26 — in the status of “active disease”. Among patients transplanted into CR2, the probability of relapse was 20 %, and the overall survival rate was 80 %. Among patients transplanted outside of CR2, the probability of achieving CR2 was 77 %, the probability of relapse was 50 % and overall survival (OS) 58 %. The probability of OS in the group as a whole reached 52 %. The most significant prognostic factors of an unfavorable outcome were early relapse, refractory course of relapse, M7 variant of AML, complex karyotype and rearrangements of the ETV6 gene, combined (“bone marrow + CNS damage + non-hematopoietic tissue”) relapse and relapse after HSCT performed in CR1.

Conclusion. About 50 % of patients with relapses of AML can be cured with the help of high-dose chemotherapy and allo-HSCT.

Introduction. There are several forms of the L-asparaginase which are characterized by differences in the half-life, the spectrum of toxicity as well as other factors.

Aim — to determine the incidence of different types of L-asparaginase toxicity in adult patients with Ph-negative acute lymphoblastic leukemia (ALL) treated according to the ALL-2016 protocol.

Materials and methods. From December 2016 to February 2023 the multicenter prospective randomized study “ALL-2016” included 313 patients with newly diagnosed Ph-negative ALL. Information about the 256 patients who had toxicity of native L-asparaginase was entered into an electronic database. The ratio of men and women was 155:101. The median age was 32  (18–54) years. We analyzed 1253  courses of therapy that included the administration of L-asparaginase.

Results. L-asparaginase toxicity and adverse reactions were diagnosed in 67 (26 %) of 256 patients. Of the 1253 courses, 102 (8 %) had complications associated with the administration of this drug. Grade 1–2 toxicity of L-asparaginase was diagnosed in 34 (51 %) patients: allergic reaction — in 6 (18 %), thrombosis of brachiocephalic veins associated with the installation of a central venous catheter — in 2 (6 %), increased pancreatic amylase in blood serum and diastase in urine, without clinical signs of pancreatitis — in 3 (9 %), lower protein-synthesis function of liver — in 23 (68 %), hepatotoxicity — in 15 (44 %). Grade 3–4 toxicity of L-asparaginase was diagnosed in 33 (49 %) patients, of which 22 (67 %) required discontinuation of the drug. The median of the development of complications of L-asparaginase was the third administration. None of the patients died as the result of the toxicity of native form of the drug. The 5-year overall survival (OS) and the probability of relapse (PR) in the group of patients in which L-asparaginase was discontinued at the stage of induction of remission and in the group of patients who continued L-asparaginase treatment at remission consolidation and maintenance therapy did not differ significantly: OS — 89 % vs 70 % (p = 0.0921), PR — 47 % vs 33 % (р = 0.8633).

Conclusion. In adult patients, L-asparaginase withdrawal due to toxicity, in most cases, occurs at the stage of the remission induction. It is possible that the replacement of the native form the drug to the pegylated one in adult patients with ALL, in whom L-asparaginase is canceled at the stage of remission induction, improves long-term survival rates.

Introduction. Currently, Ibrutinib is one of the most effective drugs for relapsed and refractory chronic lymphocytic leukemia treatment. In most patients with CLL, ibrutinib causes persistent remissions, but in some patients the disease progresses. Ibrutinib resistance in most cases is associated with the C481S mutation, which corresponds to the c.1441T>A and c.1442G>C substitutions in the BTK gene, however, other variants also exist.

Aim — to evaluate variable allele fraction of the BTK gene mutations in patients with relapsed chronic lymphocytic leukemia using the in-house allele-specific real-time PCR test.

Materials and methods. The study included material from 102 cases: 39 CLL patients with disease progression on ibrutinib therapy, 24 CLL patients with disease progression on the FCR/FCR-lite protocols, and 38 CLL treatment-naive patients. The control group included 118 patients with non-neoplastic hematological diseases.

Results. Using in-house using AS-PCR, we detected the c.1442G>C mutation in 20 out of 39 CLL patients with progression on ibrutinib therapy. Mutation c.1442G>T was detected in 2 patients. In a single patient, two mutations were detected simultaneously: c.1441T>A and c.1442G>C. Another single patient had a combination of three mutations: c.1442G>C, c.1442G>T and c.1442G>A. In 15 patients with progression on ibrutinib therapy, mutations in the BTK gene were not detected. In treatment-naive CLL patients, in the group treated with FCR/FCR-lite regimens, and in the control group of patients with nonneoplastic diseases, mutations in the BTK gene were not detected.

Conclusion. Variable allele fraction of exon 15 BTK gene mutations in the patients with CLL progression was successfully determined using in-house AS-PCR test: 50 % of patients had one mutation, 5 % had two mutations, and 2.5 % had three mutations in the BTK gene. Timely detection of these mutations before clinical recurrence may facilitate effective treatment strategy. Since clinical manifestations of ibrutinib resistance appear after an average of 1–2 years, we suggest monitoring BTK mutation load every 3 months in patients with CLL before relapse during treatment with ibrutinib.

Introduction. To improve the infectious safety of blood products, methods of pathogen inactivation in the donor container are used. Two technologies for pathogen inactivation in platelet concentrates have been approved in Russia: Intercept (amotosalen and ultraviolet A) and Mirasol (ribofl avin and ultraviolet).

Aim — to study the quality parameters of stored pathogen-reduced platelet concentrates.

Materials and methods. The platelet concentrate obtained by automatic plateletpheresis and resuspended in plasma was subjected to pathogen inactivation (PI), and samples were taken for research on the first day of storage before and after PI, as well as on the third and fifth days of storage. The volume of the dose and the number of cells were determined in 60 samples: 30 each, which underwent PI using the Intercept and Mirasol methods. The study of the pH level was performed in 46 platelet concentrates treated with Intercept and 38 containers treated with Mirasol. The characteristics of donors were also taken into account: gender, age, height, weight, and number of donations. The results were evaluated by descriptive statistics and analysis at a significance level of p < 0.05.

Results. In the compared groups, there were no differences in the gender of donors, their donor experience, and anthropometric and hematological parameters. The number of platelets within 3 days in both groups did not differ both from the initial one and between the groups. On day 5, the number of Intercept platelets remained unchanged, and the number of Mirasol platelets significantly decreased both compared with the baseline (425.2 ± 31.0 × 10⁹  vs. 519.6 ± 31.2 × 10⁹, respectively, p < 0.001) and relative to Intercept platelets (425.2 ± 31.0 × 10⁹ vs. 501.9 ± 32.8 × 10⁹, respectively, p < 0.001). During the storage of platelet concentrates, the internal environment of the containers changed to the acidic side, and on day 5, the pH of Mirasol platelets was significantly more acidic than in the comparison group (6.51 ± 0.15 vs. 6.93 ± 0.15, respectively, р < 0.05).

Conclusion. It was found that on day 5 of storage of Mirasol-platelets, the number of cells and pH significantly decreased compared to Intersept-platelets.

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. Internationally published data about the course of COVID-19 in patients with congenital bleeding disorders (CBDs) are limited. There are questions about how COVID-19 affects the course of CBDs and, conversely, how CBDs affect the course of coronavirus infection.

Aim — to analyze the course of COVID-19 in patients with CBDs in Russia.

Materials and methods. A cross-sectional survey was conducted at the National Medical Research Center for Hematology (Moscow) for the period from June 25 to July 31, 2022. A cluster of 187 patients from different regions and cities of Russia were interviewed with a questionnaire based on survey administration software (Google forms) containing 27 questions.

Results. COVID-19 affected 115 (62 %) of 187 surveyed patients and 22 (19 %) patients suffered from coronavirus infection twice. Hospitalization was required for 14 (12 %) patients with an average age of 42 years (10 patients with severe hemophilia A, 1 patient with moderate hemophilia B, 2 patients with von Willebrand disease and 1 patient with hypoproconvertinemia). During COVID-19 bleeding was observed in 9 (8 %) patients and was represented by hemarthrosis, ecchymosis, hematomas, nosebleeds, menorrhagia, hemorrhoidal bleeding, hemorrhage in the eyeball. There were no cases of thrombosis among 115 COVID-19 patients. Among patients with CBDs who had COVID-19, compared with patients who had not COVID-19, von Willebrand disease was statistically significantly more common (p = 0.04). Changes in the course of CBD after COVID-19 were noted by 21 (18 %) of 115 patients: 11 (10 %) of those who were ill noted increased joint pain, 9 (8 %) complained of joint pain that had not been previously experienced; 10 % of patients described changes of hemorrhagic syndrome.

Conclusion. The probability of hospitalization of patients with CBDs and COVID-19 older than 40 is statistically significantly higher. Von Willebrand disease can be considered as a potential risk factor for COVID-19. Given the absence of cases of thrombosis in the interviewed group of patients, the results of the study suggest that the presence of hypocoagulation in patients with CBDs may be a protective pathophysiological mechanism that prevents the development of COVID-19-associated thrombotic complications.

 Introduction. Preoperative anemia which is present in 25–40 % of cardiac surgery patients increases the risk of adverse postoperative outcomes leading to higher medical expenses. The tendency to restrict allogenic transfusion rate has led to the search for new pharmacological solutions to correct anemia in the perioperative period, nevertheless the usage of intravenous iron preparations in cardiac surgery is still not a generally accepted standard of treatment.

Aim — review of the literature about the effects of perioperative intravenous iron therapy on the clinical outcomes in cardiac surgery.

Main findings. The use of intravenous iron preparations during the perioperative period in cardiac surgery results in better hemoglobin dynamics, iron repletion and less demand for allogenic transfusions. Anemia correction and lower transfusion rate might improve surgery outcomes such as mortality, intensive care unit length of stay and hospital length of stay. Iron repletion, regardless of presence of anemia, might improve the results of 6-minute walk test and patients’ quality of life after surgery. The optimal time for intravenous iron therapy in cardiac surgery is 10–14 days before surgery or immediately after the intervention. Ferric carboxymaltose can be administered in a single injection/infusion shortly before or after surgery.

Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic method and enables to assess viscoelastic profiles of whole blood in various clinical settings. ROTEM-guided bleeding management has become an essential part of patient blood management (PBM) which is an important concept in improving patient safety. Here, ROTEM testing and hemostatic interventions should be linked by evidence-based, setting-specific algorithms adapted to the specific patient population of the hospitals and the local availability of hemostatic interventions. Accordingly, ROTEM-guided algorithms implement the concept of personalized or precision medicine in perioperative bleeding management (“theranostic” approach). ROTEM-guided PBM has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs. Accordingly, several randomized-controlled trials, meta-analyses, and health technology assessments provided evidence that using ROTEM-guided algorithms in bleeding patients resulted in improved patient’s safety and outcomes including perioperative morbidity and mortality. However, the implementation of ROTEM in the PBM concept requires adequate technical and interpretation training, education and logistics, as well as interdisciplinary communication and collaboration.

Introduction. Haemovigilance is the set of surveillance procedures covering the entire blood transfusion chain, from the donation and processing of blood and its components, through to their provision and transfusion to patients, including patient follow-up. The United Kingdom (UK) haemovigilance system has been developing for 25 years and is one of the world's leading hemovigilance systems.

Aim — to review the analysis of adverse events in the UK blood service in 2021.

Methods. Analysis of the British haemovigilance system report for 2021.

Results. Blood transfusion remains safe in the UK, with a risk of death from a blood transfusion of 0.92 per 100,000 components issued. Transfusion delays and pulmonary complications (mostly circulatory overload) were responsible for 77.1 % (27 out of 35) of blood transfusion-related deaths in 2021. Errors (including near miss cases) still make up the majority of reports. In 2021, 2569 out of 3161 (81.3 %) of all reports were associated with errors. Prerequisites for reactions still make up a significant proportion: 1155/3161 (36.5 %) incidents. Understaffing, lack of proper training, poor supervision and poor safety culture have been identified as contributing factors to numerous incidents. They need to be addressed urgently to reduce the risk to patient safety. Ensuring the safety of process-based transfusions through a multi-pronged approach, proper training, appropriate resources, user-centric design, and learning by doing are essential. Reassignment warnings in laboratory health information systems continue to contribute to error reporting. Trends in abnormal transfusion reactions such as febrile, allergic, hypotensive and hemolytic reactions are similar to previous years. All personnel involved in blood transfusion should be competent and confident in recognizing and appropriately treating transfusion reactions in recipients.

Conclusion. Haemovigilance is an important tool for improving the efficiency and safety of blood transfusion.

Introduction. Identical twins are a unique model that can be used to assess the concordance of various diseases, including acute leukemia. It should be noted that acute leukemia is characterized with high concordance in cases of monovular twins or placentas adhesion, which confirms the model of development of this disease in the prenatal period.

Aim — to present a clinical case of successful diagnosis and treatment of acute lymphoblastic leukemia in identical twins.

Main findings. Clinical cases demonstrate the development of common-variant of B-cell precursor acute lymphoblastic leukemia in identical twins with three months interval. The disease course of one of the brothers was characterized by relapses, but treatment with highly effective protocols usage achieved 15-year remission without allogeneic stem cell transplantation. In case of second twin, disease-free life expectancy is 22 years.

Introduction. Blood collection technologies were of great importance during the Great Patriotic War. This was due to the need to increase the shelf life, simplify the transportation process and ensure the safety (including the exclusion of bacterial contamination) of transfusions.

Aim — to describe the technologies for blood collection and transfusion, alternatives to blood transfusion and measures aimed at organizing the collection and clinical use of blood in the Great Patriotic War.

Main findings. This article describes the process of collecting donated blood during the Great Patriotic War. Methods of preparing a donor for the procedure, technological methods at the time of taking blood from primary and repeated donors (anesthesia, intervals between donations, etc.) are shown. Methods for the preparation of citrated blood, preserved blood, cadaveric blood, defibrinated and placental blood are described. The labor-intensive procedure used in those years required a scrupulous attitude to the preparation of equipment and solutions. Marking, storage and transportation of donated blood were of great importance.