Introduction. Long-term survival rates in patients with refractory/relapsed acute B-lymphoblastic leukemia/lymphoma (r/r B-ALL/LBL) remain extremely poor. The introduction of Chimeric Antigen Receptor T-cell (CAR T) therapy into clinical practice offers a new promising treatment option for this group of patients.

Aim: to evaluate the efficacy of anti-CD19 and anti-CD19/22 CAR T-cell therapy in 8 adult patients with r/r B-ALL/LBL.

Materials and methods. Between January 1, 2020 and July 1, 2024, as part of the NRCH-CAR T-2020 pilot study the National Medical Research Center for Hematology conducted anti-CD19/anti-CD19/22 CAR T cell therapy for 8 adult patients with refractory B-ALL/LBL under the hospital exemption rule. The median age was 28 (19–37) years. The male to female ratio was 5:3. The median number of previous treatment lines was 3 (2–7). All patients underwent leukocytapheresis and lymphodepletion with fludarabine (120 mg/m2 ) and cyclophosphamide (750 mg/m2 ) on days –5 to –2 of therapy. Cytokine release syndrome (CRS) prophylaxis was administered with tocilizumab on day 0 before CAR-T lymphocyte administration.

Results. 8 patients with r/r B-ALL underwent 11 infusions of academic anti-CD19 and anti-CD19/22 CART-lymphocytes. Six patients were infused with anti-CD19 CAR T-cells, 2 patients with anti-CD19/CD22 CAR T-cells. Six patients underwent infusion of autologous CAR T-cells, and 2 patients with allogeneic CAR T-cells. The median of infused CAR T-lymphocytes was 0.625 (0.1–2.5) × 106 CAR+ cells/kg. Immune complications were noted in 3 of 8 patients (37.5 %): CRS in 2 patients, ICANS (immune effector cell-associated neurotoxicity syndrome) grade 3, and CRS grade 1 in 1 patient. All patients achieved complete remission by day 28 after CAR T-therapy. The median follow-up period was 12 months (2–42 months). Three patients (37.5 %) died from B-ALL/LBL relapse or progression. Five patients (62.5 %) are under observation. Three of these patients, who achieved complete remission after CAR T therapy, underwent allogeneic hematopoietic stem cell transplantation (alloHSCT).

Conclusion. CAR T-cell therapy is a promising treatment option for patients with r/r B-ALL. Allo-HSCT after CAR T likely resulted in optimistic long-term survival outcomes.

Introduction. Systemic chemotherapy (CT) has significantly improved the treatment outcomes of classical Hodgkin lymphoma (cHL). However 20–30% of patients experience disease relapse and 10% develop refractory disease. The choice of secondline therapy for patients with relapsed or refractory (r/r) cHL often depends on the experience of the hospital and physician.

Aim: To evaluate the effectiveness of autologous hematopoietic stem cell transplantation (auto-HSCT) and the role maintenance therapy of nivolumab according to the Nivo-BeGEV protocol in r/r cHL.

Materials and methods. From 2019 to 2025, 134 patients with r/r cHL who received immunochemotherapy according to the Nivo-BeGEV protocol were included in a prospective clinical study. The median age was 32.5 years (range 18–64), 63 (47%) were female and 71 (53%) male. Auto-HSCT was not performed in 19 (14.1%) patients, however they received maintenance therapy of nivolumab. Auto-HSCT was performed in 115 patients, of whom 57 (49.6%) received nivolumab maintenance therapy, while 58 (50.4%) did not.

Results. In the group of r/r cHL patients without risk of relapse and progression, no adverse events were recorded. For patients treated with the Nivo-BEGEV protocol followed by auto-HSCT and nivolumab maintenance progression-free survival (PFS) rates were 94% at 12 months, 89% at 24 months and 89% at 36 months. Patients who underwent only auto-HSCT or only nivolumab maintenance had PFS rates of 88%, 78% and 71% respectively (p = 0.1617).

Conclusion. The study demonstrates the high significance of performing auto-HSCT combined with nivolumab maintenance therapy in patients with r/r cHL.

Introduction. Cytological examination of bone marrow aspirate is a fundamental tool in the diagnosis of hematological diseases. The reference intervals for myelogram parameters serve as the primary guide for interpreting and assessing changes in the cellular elements of bone marrow. However, the reference intervals vary in the myelogram report forms of different healthcare organizations (HCOs).

Aim. To analyze the reference values of myelograms used in “anchor” HCOs of the constituent entities of the Russian Federation.

Materials and methods. An analysis of the reference intervals for myelogram parameters used in the “anchor” HCOs of 83 constituent entities of the Russian Federation was conducted using standard methods of descriptive statistics, expert ranking, and assessment.

Results. Significant differences were identified in myelogram parameters considered as normal across different constituent entities of the Russian Federation. Reference values for myelogram parameters were absent in 1 (1.2 %) HCOs. Only 4 (4.8 %) HCOs specified the sources of their reference intervals. The remaining 78 HCOs used reference intervals from unknown sources. The analysis revealed significant disparities in the myelogram parameters accepted as normal. The upper limit for neutrophilic myelocytes varied from 10.0 % to 16.9 %, for lymphocytes from 10 % to 23.7 %, and for erythrokaryocytes from 25.0 % to 32.5 %. The permissible values for the count of blast cells in the myelogram also varied. The upper threshold for a normal blast cell count was considered ≥5 % in 7 HCOs and <1 in 5 HCOs.

Conclusion. The lack of uniform, generally accepted normal myelogram parameters complicates the diagnosis and interpretation of laboratory test results by clinicians. This article provides a brief historical overview and recommendations for standardizing reference intervals for myelogram parameters.

Introduction. The hematopoietic system is sensitive to ionizing radiation. At the same time, research on hematopoietic effects in cohorts of individuals who are chronically exposed to ionizing radiation is quite limited.

Objective. To evaluate red blood cell and hemoglobin levels, and to analyze their changes over time in individuals chronically exposed to ionizing radiation.

Material and methods. The study cohort consisted of nuclear workers of the Mayak PA who were hired between 1948 and 1952, totaling 7,391 individuals. These workers were followed for a period of 15 years starting from their date of hire. The analyzed dataset included 156,490 peripheral blood counts. At the end of the follow-up period, the mean accumulated red bone absorbed dose of gamma rays from external exposure was 0.81 ± 0.79 Gy for males and 0.55 ± 0.62 Gy for females. The mean annual gamma dose was 0.10 ± 0.20 Gy for males and 0.07 ± 0.15 Gy for females, and the mean maximum annua gamma dose was 0.33 ± 0.39 for males and 0.22 ± 0.27 Gy for females.

Results. The mean red blood cell and hemoglobin levels in the study cohort of workers remained within the normal physiological range, showing only slight fluctuations throughout the entire follow-up period. Both red blood cell and hemoglobin levels in the peripheral blood decreased significantly in the first few years after the beginning of contact with ionizing radiation sources, when the highest annual absorbed gamma doses in red bone were recorded for both male and female workers. After these initial years, red blood cell and hemoglobin levels eventually returned to normal. The differences were statistically significant when the levels in first years of employment were compared to the levels reported during pre-employment health check-ups. However, no complete recovery to the pre-employment levels was observed. The hemoglobin concentration also remained within the normal physiological range throughout the entire follow-up period. However, after the recovery period, it gradually decreased until the end of the follow-up, compared to the pre-employment level. The analysis of these blood parameters in relation to gamma-ray dose from external exposure revealed a significant association of red blood cell and hemoglobin concentration with the radiation dose (p < 0,05).

Conclusion. Red blood cell levels and hemoglobin concentrations registered at the pre-employment health check-up were significantly lower in females than males. In the first 15 years of employment, the mean red blood cell and hemoglobin levels were significantly decreased compared to the pre-employment levels. The red blood cell level and hemoglobin concentration were significantly associated with the gamma-ray dose from external exposure.

Introduction. The development of therapy resistance and relapses of acute myeloid leukemia (AML), especially in the intermediate prognosis group, may be due to the molecular genetic heterogeneity of tumor cells. Chromosomal microarray analysis (CMA) can detect microdeletions, duplications, and copy-neutral loss of heterozygosity (cnLOH) which may be associated with a response to therapy.

Aim: to evaluate tthe frequency of copy number aberrations and cnLOH in leukemogenesis-associated genes in patients with intermediate-stage AML and and their relationship to survival and response to treatment.

Materials and methods. The study included 35 patients with de novo AML from the intermediate prognosis group for ELN2017. Copy number analysis by CMA was performed for a panel of 36 genes associated with leukemogenesis. The reference group included 102 healthy individuals without oncohematological disorders who also underwent comparable CMA testing.

Results. Genomic aberrations were detected in 91.18 % of patients, most often in the genes of chromatin modifiers (64.7 % patients) and tumor suppressor genes (64.7% patients). The cnLOH type (PHF6, SMC1A, BKORL1) prevailed. KMT2A duplications occurred only in AML patients — 14.3 % (p < 0.001) and were associated with worse survival (log-rank P = 0.05). Combinations of genomic alterations involving 4–7 functional gene groups were found in 20.6% of patients.

Conclusion. Driver gene aberrations, especially KMT2A duplications, are associated with an unfavorable clinical outcome in AML with an intermediate prognosis.

Introduction. The use of allogeneic blood components in cardiac surgery is associated with the development of complications. One of the strategies for minimizing unjustified transfusions is the use of risk stratification models for transfusion therapy. Their goal is to predict the likelihood of using blood components in a particular patient based on clinical indicators.

Objective. To study the possibility of using a risk stratification model for transfusion therapy.

Materials and methods. The criteria for inclusion in the study were met by patients over 18 years of age who underwent emergency and planned open-heart surgery performed between January 01, 2024 and December 31, 2024. The endpoint was considered to be allogeneic blood transfusion, which was understood to mean the clinical use of one or more units of erythrocyte-containing components, any type of plasma or concentrate throughout the duration of hospitalization. Discrimination assessment was performed using the AUC-ROC method. The calibration was evaluated using the Hosmer-Lemeshov test. Descriptive analysis was performed using categorical variables expressed in absolute numbers and percentages. The quantitative variables were expressed as means and standard deviations. Statistical analysis was performed using Microsoft Excel 2010.

Results. A total of 218 patients were included in a single-center, observational, retrospective study. The accuracy of transfusion prediction was 0.67 95 % CI. The Hosmer-Lemeshov test demonstrated systematic calibration errors. In low–risk areas, the model overestimated the probability of transfusion, while in high-risk areas it underestimated it.

Conclusion. The use of this model makes it possible to optimize the appointment of donated blood and reduce the number of unjustified transfusions. For clinical use, adaptation to local conditions is required.

Introduction. Over the period from 2019 to 2023, there has been an increase in the prevalence of hematological diseases (malignant and non- malignant) (HemD). This situation once again highlights the need to ensure the availability of accessible specialized medical care (SMC) and its continuity at all stages, which is possible in a hematological day hospital (HDH).

Aim: To assess the availability of HDH in the public healthcare sector of the Russian Federation (RF), its Federal Districts (FD), and constituent entities.

Materials and methods. Information from the reporting industry forms of federal statistical observation No. 14-DS (FFSN No. 14-DS) for 2019–2023 and data from territorial compulsory health insurance funds for 85 constituent entities of the Russian Federation were analyzed.

Results. By 2023, hematological services were organized in 85 of the 89 constituent entities of the RF, while HDH were only available in 63 (74%). HDH operate both in 24-hour hospitals (CH) and in outpatient settings. The number of hematological beds for adults increased by 21.7% from 2019 to 2023, from 533 to 636 beds. From 2019 to 2023, the provision of adult population with HDH in the Russian Federation increased by 28% from 0.046 to 0.059 per 10,000 adults respectively. A positive trend in the analyzed indicators was observed in all federal districts, with the exception of the Far Eastern federal district, where there was a sharp decrease in the provision of HDH from 0.06 to 0.03 due to a change in a change in bed profile to oncology. The average increase in the number of hospitalizations in the HDH per 10,000 adult populations between 2019 and 2023 was 332% (from 2.9 to 12.53). The average duration of treatment in the HDH in 2019 and 2023 in the Russian Federation decreased by 16%, from 6.9 to 5.8 days, respectively. In 2023 SMC in HDH was provided in 55,930 cases in the Russian Federation, of which 26,117 (47%) were at the outpatient stage. To support HDH operations, physicians from previously established hematology departments were involved. For the financial support of HDH, the formulation of the clinical-statistical group ds19.033 “Hospitalization for diagnostic purposes with molecular genetic and/or immunohistochemical testing or immunophenotyping” in the State Guarantees Program was amended, enabling high-tech diagnostics of hematological diseases.

Conclusion. HDH are insufficiently integrated into the healthcare system of the RF and are absent in 22 regions. In the constituent entities of the RF, it is necessary to continue organizing HDH, which are an economically viable form of providing emergency medical care to the adult population, allowing for the effective examination and treatment of hematological patients while maintaining their usual quality of life.

Acknowledgment. The authors express their gratitude to the heads of the hematology service in the regions of the RF, as well as to the staff of the FSBI Russian Research Institute of Health of the Ministry of Health of the RF for the materials provided and for their assistance in selecting information materials.

Introduction. Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare thrombotic microangiopathy that occurs due to a congenital deficiency of the ADAMTS13 enzyme. It can manifest both in childhood and in adulthood.

Aim: to analyze the manifestations and course of cTTP in adult patients. Materials and methods. Hemoglobin and platelet concentrations, a direct Coombs test, lactate dehydrogenase (LDH), ADAMTS13 activity, and ADAMTS13 inhibitor were studied in patients with suspected thrombotic thrombocytopenic purpura (TTP). In patients with ADAMTS13 activity< 10% and the absence of an ADAMTS13 inhibitor, the concentration of the ADAMTS13 antigen and mutations of the ADAMTS13 gene were studied. cTTP was diagnosed in the absence of ADAMTS13 inhibitor and the detection of mutations in ADAMTS13 gene.

Results. cTTP was diagnosed in 11 (9.5 %) patients (10 women, 1 man) among 115 adult patients with TTP. Mutations of ADAMTS13 gene were detected in all patients. Disease onset occurred between the ages of 20 and 33 years 33 (median 22 years). In 9 out of 10 women, the onset of the disease was associated with pregnancy. During TTP manifestation all patients had thrombocytopenia ((4–31)×109 /L, median 14×109 /L), anemia (hemoglobin 67 g/L), increased LDH activity (median 1300 U/L), low ADAMTS13 activity (median 2 %), and low ADAMTS13 antigen concentration (median 0.008 IU/ml). Neurological symptoms were present in 5 (45 %) of the 11 patients, and 2 of the 11 patients developed chronic renal failure. In clinical remission, all patients had normal ranges of hemoglobin, platelets and LDH activity, however ADAMTS13 activity remained low (0–18 %, median 7.5 %). Treatment during exacerbation included plasma transfusions; 8 patients underwent plasma exchange. Prophylactically, most patients received plasma at a dose of 15 mL/kg every 3–4 weeks. Three patients were treated with recombinant ADAMTS13 at a dose of 40 IU/kg intravenously once every 2 weeks. The therapy was well tolerated, and there was an increase of platelet level after drug administration.

Conclusion. cTTP can manifest in adulthood. In remission, cTTP patients need laboratory monitoring and preventive treatment.

Introduction. The blood coagulation factor XII (FXII) is involved in opposing processes of hemostasis: contact activation of the intrinsic pathway of blood coagulation and fibrinolysis. What might the clinical picture of FXII deficiency present with: bleeding, thromboses or be asymptomatic? The issue remains debatable.

Aim: To present the clinical and laboratory characteristics of patients with congenital FXII deficiency in the Russian population.

Materials and methods. A retrospective study included 29 of 212 patients with FXII deficiency who underwent genetic analysis, confirming the hereditary nature of the disease.

Results. The mean APTT in the study group was 187 seconds (control 29–38 sec.). The mean FXII activity was 20%. The most common mutation of F12 in the Russian population was the nucleotide substitution c.1681 –1 G>A. The reasons for contacting a hematologist and conducting diagnostics of the disease were: preoperative examination in 9 (31%) patients; abnormalities in the coagulogram during examination prior to pregnancy planning or during examination for a chronic disease in 8 (28%) patients; bleeding — in 7 (24%) patients; abnormalities in the coagulogram during screening in pregnancy in 2 (7%); family examination in 2 (7%) patients. In 21 (72%) of 29 patients, the clinical picture was represented by hemorrhagic manifestations. Thrombotic events were noted in 2 (7%) of 29 patients. Among 16 (80%) women with a history of pregnancy, miscarriages occurred in 6 (38%).

Conclusion. The diagnosis of hereditary FXII deficiency is most often established during preoperative examination. However, 24% of patients consulted a hematologist with complaints of hemorrhagic manifestations, mostly mild or moderate. Surgical bleeding was noted in 21% of patients. The obstetric history of more than a third of women was complicated by miscarriages. In patients with hereditary FXII deficiency, it is necessary to be wary of mild spontaneous bleeding, surgical bleeding, miscarriage and, to a lesser extent, thromboses.

Introduction. The high prevalence of acute cardiovascular diseases and the significant mortality associated with them sustain ongoing interest in the mechanisms of thrombus formation and the factors preceding thrombosis, particularly in the arterial bed.

Aim: to assess changes in the quantitative and qualitative characteristics of the metalloprotease ADAMTS13 and von Willebrand factor (vWF) antigen in patients with ischemic stroke (IS) who underwent mechanical thrombectomy, depending on the neurological deficit and functional outcome of the disease.

Materials and methods. The study included 52 patients aged 36 –95 years (median age 72 years) who received inpatient treatment for IS, in whom cerebral angiography revealed thrombosis of the intracranial segments of the brachiocephalic arteries followed by mechanical thrombectomy. All patients were tested for vWF antigen, ADAMTS13 activity, ADAMTS13 antigen, and antibodies to ADAMTS13. Venous blood samples for the study were obtained upon hospital admission, 24 hours, and 120 hours after hospitalization.

Results. The vWF:Ag values in the group of IS patients with a fatal outcome upon admission exceeded the upper limit of the reference interval but did not statistically differ from the vWF:Ag values in the group of IS patients with a favorable outcome (197.7 % [139.8–255.6] vs. 142.1 % [109.2–195.5], p = 0.071). The vWF:Ag levels at 24 hours and 120 hours in patients with a fatal hospitalization outcome were significantly higher compared to those in recovered patients (236.1 % [201.6–288.6] and 345.6 % [331.7–382.1] vs. 185.2 % [135.1–205.8] and 198.4 % [149.9–256.4]; p = 0.005 and p = 0.001, respectively). In the group of patients with severe IS, the median vWF:Ag level at 120 hours after admission was significantly higher compared to that in the group of patients with mild and moderate IS (291.7 % [199.7–363.2] vs. 187.4 % [130.5–250.9], p = 0.011). No significant differences in the medians of quantitative and qualitative characteristics of the ADAMTS13 metalloprotease were found between groups formed based on either disease outcome or severity of neurological deficit (p > 0.05).

Conclusion. Elevated vWF:Ag in patients with an unfavorable outcome of IS indicates endothelial dysfunction and the potential realization of a prothrombotic state. Since the fatal outcome was accompanied by infectious complications, the increase in vWF:Ag should be considered as a reaction of an acute-phase marker. No significant differences in the quantitative and qualitative indicators of ADAMTS13 were found between patient groups with different functional outcomes and neurological deficits.

Introduction. Burkitt lymphoma is an aggressive B-cell lymphoma characterized by pathomorphological, immunophenotypic, and cytogenetic features that are the main criteria for its diagnosis. Burkitt lymphoma with isolated involvement of the central nervous system (CNS) is an extremely rare nosological form of primary lymphoma of the central nervous system. The small number of observations in the literature does not allow us to fully determine the main clinical, radiological and age-related features of this lymphoma, as well as standardize the treatment tactics for patients with primary Burkitt lymphoma of the central nervous system.

Aim: to present a clinical case of a patient with primary Burkitt lymphoma of the CNS with damage to the right hemisphere of the cerebellum and brainstem with compression of the cavity of the fourth ventricle.

Main findings. The diagnosis was established based on the basis of pathomorphological and immunohistochemical examination of the removed neoplasm of the fourth ventricle and was confirmed by in situ fluorescence hybridization using the DNA probe MYC gene break apart detection dual-color probe, which revealed a classical translocation involving the MYC/8q24 gene. The patient underwent 4 courses of chemotherapy under the LB-M-04 program, at the end of which a regression of the neoplasm was achieved.