Introduction. The current overall effectiveness of acute myeloid leukemia (AML) treatment is largely ensured by the integration of transplantation technologies, but not all patients who are indicated to undergo transplantation of allogeneic hematopoietic stem cells (allo-HSCT) can reach this stage.

Aim: to analyze the time and volume of the implementation of allo-HSCT in patients with AML in the first complete remission (1CR).

Materials and methods. Between January 2020 and December 2023, 477 AML patients from 43 different regions of the Russian Federation were referred to the NMRC for Hematology for the possibility of performing allo-HSCT. In this cohort of patients, the following time parameters were analyzed: days from diagnosis of AML to primary treatment at the transplant center, from primary treatment to search for a donor (related or non-related), from diagnosis of AML to allo-HSCT, from the achievement of 1CR to allo-HSCT.

Results. 175 (36.7 %) patients, agreed upon by the Transplant Commission, were selected to undergo allo-HSCT. Of these, only 163 patients, who had allo-HSCT performed before January 2024, were included in further analysis. It was not possible to implement allo-HSCT in the other 236 agreed upon cases due to the following reasons: refusal of the patient — 110 (46.6 %), relapse — 48 (20.3 %) patients, death — 23 (9.7 %) patients. Median time from 1CR to allo-HSCT was 6.8 (0.3– 26) months for all patients: for a related fully compatible donor 5.8 (0.5–26.0) months, for a haploid donor — 6.1 (0.3–23.5) months, in case of non-related — 8.0 (0.6–8.6) months. In 5 years, the NMRC for Hematology managed to reduce the time to the general allo-HSCT in 1CR for patients with AML from 6.5 months in 2018 to 5.8 months in 2023. Also, under the current “AML-21” protocol, the time from 1CR to allo-HSCT in patients included in the multicenter study was minimized to — 4.8 (0.33–11.0) months, and for AML patients from the poor prognosis group — 3.4 (0.33–8.0 months).

Conclusion. In addition to achieving full, optimally — MDR-negative remission, the absence of severe concomitant pathology, and the presence of a donor, the time factor must also be considered. In order to cure more AML patients, it is necessary to bring the implementation of allo-HSCT to the earliest possible date after achieving 1CR.

Introduction. Achieving complete remission and prolonging event-free survival is the primary task of chemotherapeutic treatment for patients with acute myeloid leukemia (AML). Supportive therapy is a possible way to maintain complete remission.

Aim: to compare two variants of supportive treatment (5+5 and 6-MP + Mtx) in patients with AML in the first complete remission after completion of the induction and consolidation programs.

Materials and methods. The single-center randomized study included 34 AML patients treated from 2017 to 2021. The median age was 36 (18–56) years, the ratio of men to women was 18:16. After completing the induction and consolidation program, randomization was performed for different branches of supportive chemotherapy: 5+5 (cytarabine 50 mg/m² 2 times/day, mercaptopurine 60 mg/m² days 1–5, a total of 6 courses) — first group (18 patients), and 6-MR + Mtx (6-mercaptopurine 50 mg/m² daily, methotrexate 15 mg/m² once/week) — second (16 patients). Courses of maintenance therapy were conducted until the total completion of treatment, the implementation of allogenic hematopoietic stem cell transplantation (allo-HSCT), the development of relapse, or death of the patient.

Results. The two-year overall survival in the 5+5 group was 93 %, in 6-MP + Mtx group 68 % (p = 0.0814). Mortality in both groups was associated with complications in the post-transplant period. The actual OS and the hypothetical one — without performing allo-HSCT, did not differ. Thus, the fact of performing allo-HSCT does not affect the effectiveness of maintenance therapy courses. The two-year disease-free survival rate (DFS) was 66 % in the 5+5 group and 63 % in the 6-MP + Mtx group (p = 0.42). From the time of randomization, 8 patients (24 %) have relapsed and 1 patient died from complications after allo-HSCT.

Conclusion.  During treatment under the maintenance therapy programs 5+5 and 6-MP+Mtx, similar OS and RFS were achieved. During 5+5 program, hospitalization in a day hospital is required. The 6-MP+Mtx program has similar effectiveness, however, the entire period of supportive treatment can be carried out on an outpatient basis but lasts 24 months compared to 6 months when using the 5+5 program. The choice of maintenance therapy according to the 5+5 program is optimal from the point of view of the quality of life of patients.

Introduction. Primary mediastinal large B-cell lymphoma (PMBCL) is a rare non-Hodgkin lymphoma. Considering the immunophenotype of PMBCL, which differs from diffuse large B-cell lymphoma (DLBCL), Microsatellite Repeat (MSR) aberrations in regions flanking PD-L1/PD-L2 and CIITA genes were investigated.

Aim: to study the prevalence of MSR aberrations in 19 loci of the COrDIS Plus panel and in the regions of the PD-L1/PD-L2, CIITA genes in PMBCL and DLBCL, and to compare it with the expression level of PD-L1 and HLA-DR in PMBCL.

Materials and methods. The study included 137 patients, 86 (62,8%) with PMBCL and 51 (37.2%) with DLBCL. The analysis was conducted using the standard COrDIS Plus panel, which includes a set of primers for 19 loci of tetranucleotide repeats. The allelic imbalance (AI) of MSR close to the PD-L1/PD-L2 genes (9p24.1) (n = 68/86 (79.1%) for PMBCL, n = 36/51 (70.6 %) for DLBCL) and CIITA (16p13.13) (n = 71/86 (82.6 %) for PMBCL, n = 29/51 (56.9 %) for DLBCL) was investigated using STR analysis. Patients with homozygous inheritance for each of the studied markers were excluded from further analysis due to the inability to assess loss of heterozygosity (LOH). The expression of PD-L1 and HLA-DR was assessed by immunohistochemistry in 27/86 (31.4 %) PMBCL patients.

Results. Homozygosity for both markers near the PD-L1/PD-L2 genes was found in 5/68 (7.4 %) of PMBCL patients and 10/36 (27.8 %) of DLBCL patients (p = 0.008). Aberrations of MSR flanking the PD-L1/PD-L2 genes were detected in 33/63 (52.4%) of PMBCL patients and 5/26 (19.2 %) of DLBCL patients (p = 0.003; OR 5.8; 95% CI [2.8–18.7]). Homozygosity for both markers near the CIITA gene was identified in 8/71 (11.3%) of PMBCL patients and 7/29 (24.1%) of DLBCL patients (p = 0.13). AI near the CIITA gene was found in 24/63 (38.1 %) of PMBCL patients, while no changes in the CIITA region were observed in the DLBCL group (p = 0.0001; OR 14.3; 95% CI [2.8–262.5]). Using the COrDIS Plus panel, the frequencies of tetranucleotide repeat aberrations did not significantly differ between PMBCL and DLBCL (p = 0.78 for LOH, p = 0.17 for EMAST). No correlation was found between MSR aberrations near the PD-L1/PD-L2 and CIITA genes and the expression levels of PD-L1 and HLA-DR (p = 0.402 and 0.668, respectively).

Conclusion. A statistically significant more frequent alteration in the MSR marker profile of the PD-L1/PD-L2 and CIITA gene regions was found in PMBCL patients compared to DLBCL. Chromosomal microarray analysis in 2 out of 3 PMBCL cases revealed genetic aberrations involving the PD-L1/PD-L2 and/or CIITA genes, and AI of these genes was observed simultaneously with the MSR profile evaluation. This confirms the different pathogenesis of these diseases and suggests that the presence of AI in these loci indicates the involvement of these genes in the pathogenesis. There is no correlation between AI in the PD-L1/PD-L2 and CIITA gene regions and the expression of PD-L1 and HLA-DR, respectively.

Introduction. Myelodysplastic syndrome (MDS) is a nosology that requires examination using cytogenetic, molecular-genetic and immunophenotypic analysis of bone marrow and/or blood, as well as mandatory bone marrow trepan biopsy with pathomorphological and immunohistochemically studies. Until recently, there was no official statistical data on MDS in Russia.

Aim: to present data on the incidence and prevalence of MDS in Russia based on official statistical forms.

Materials and methods. Information from statistical form №7 «Information on malignant neoplasms» (SF No. 7) for 2022 and 2023 on the incidence and prevalence of MDS, updated at the initiative of the National Medical Research Center for Hematology, is presented. For the first time, additional lines (35–37) with information on the movement of patients, including MDS (code D46 according to ICD-10), have been introduced into table 2100.

Results. According to SF No. 7, in 2022 and 2023, 2,827 and 3,411 cases of MDS were registered, respectively. The estimated primary incidence in the Russian Federation was 0.58 and 0.50 per 100 thousand of the adult population in 2022 and 2023, respectively, and the prevalence was 2.4 per 100 thousand of the adult population. The estimated incidence of MDS by federal districts in 2022 ranged from 0.13 to 1.05 with variations from 0.03 to 2.57 per 100 thousand of the adult population, depending on the region of residence. At the end of 2023, 3001 (88 %) patients with MDS were registered under dispensary observation, of which 860 (28.7 %) were under observation for 5 years or more.

Conclusion. The obtained statistical data on the incidence and prevalence of MDS showed the high significance of the work carried out both for the subsequent improvement of the system of registration of patients with diseases of the blood system in general, and MDS, particularly the Russian Federation, and will make it possible to use this data in the planning of healthcare in the Russia.

Introduction. During enzyme replacement therapy in patients with Gaucher disease (GD) with recombinant glucocerebrosidase (GCase), regression of bone manifestations is possible, but with prolonged therapy osteonecrosis may occur. These changes may be due to impaired differentiation of multipotent mesenchymal stromal cells (MSCs).

Aim: to study changes in the MSCs of healthy donors and a patient with GD when cultured in the presence of GCase.

Material and methods. MSCs were isolated from the bone marrow of 17 healthy donors and a female patient with GD by a standard method and cultured in the presence of various concentrations of GCase after the second passage from 2 to 7 weeks. Cell proliferation and the ability to differentiate were analyzed, including after induction. The assessment was carried out by differential staining, elution, and expression of differentiation marker genes by real-time PCR.

Results. Low concentrations of recombinant GCase (0.25–1.5 U/ml) did not affect the proliferative activity of MSCs. Prolonged cultivation of MSCs in the presence of low doses of GCase led to a change in the differentiation potential of these cells in the direction of adipogenesis. Concentrations of GCase of 3–5 U/ml inhibited the proliferation of MSCs and caused significant changes in cell differentiation. High doses of the enzyme (7–10 U/ml) had a cytotoxic effect and led to cell death within one passage. The proliferative and differentiation potential of the MSCs of a patient with GD differed significantly from the cells of healthy donors in all the parameters studied.

Conclusion. The cultivation of donor MSCs in the presence of recombinant GCase alters the proliferation and differentiation potential of these cells. These changes depend on the dose of the enzyme in the medium and the duration of cultivation.

Introduction. Combined deficiency of factors V and VIII is a rare hereditary bleeding disorder with a prevalence of 1:1,000,000 in the general population, but the disease is more common in regions where consanguineous marriages are acceptable. Data on this hereditary coagulopathy in the Russian Federation are limited.

Aim: to analyze clinical and laboratory characteristics of the course of the disease in patients with hereditary combined deficiency of factors V and VIII in the Russian population.

Materials and methods. The retrospective and prospective study involved 6 patients with hereditary combined deficiency of factors V and VIII in the Russian population.

Results. The average age of patients was 50 years (32–72 years). The average age at the time of diagnosis was 40 years. Bleeding scores on the ISTH-BAT scale ranged from 17–29, with an average value of 23.5. The average value of activated partial thromboplastin time was 85 seconds, the prothrombin by Quick was 35 %, and the activity of FV and FVIII was 5.7 % and 9.0 %, respectively. The course of the disease was characterized more or less by cutaneous-mucous hemorrhagic syndrome, postoperative, obstetric-gynecological, and life-threatening bleeding.

Conclusion. Clinical and laboratory characteristics of patients expand the understanding of hereditary combined deficiency of factors V and VIII and make it possible to accelerate diagnosis verification.

Introduction. Surgical treatment of congenital heart defects in children is associated with a high incidence of early thrombotic complications. Violation of the ratio of von Willebrand factor (vWF) and ADAMTS13 metalloproteinase activity is one of the components of changes in the hemostasis system.

Aim: to study changes in the vWF-ADAMTS13 system in patients with obstructive congenital heart defects.

Materials and methods. The prospective observational cohort study included 18 newborns with isolated obstructive CHD (congenital valvular aortic stenosis, isolated coarctation of the aorta). The activity of vWF and ADAMTS13 was determined in all patients, and the dynamics of fibrin formation and thrombin generation were evaluated. The relationship between hemodynamic parameters and the Reynolds number with laboratory parameters of the blood coagulation system before correction of congenital heart defects was studied.

Results. The activity of von Willebrand factor varied from 32.1 to 242.0 %. The distribution of ADAMTS13 activity ranged from 0.83 to 1.56 IU/ml. The values of von Willebrand factor activity correlated with the average platelet volume, the initial and steady-state growth rate of the fibrin clot, as well as its size, the time to reach the peak of thrombin (negative correlation) and the rate of thrombin propagation. ADAMTS13 activity values correlated with the aortic valve annulus diameter, aortic arch and isthmus diameter, Reynolds number, and fibrin clot growth retardation. In a univariate regression analysis, aortic valve size (β = 0.540, p = 0.021) and aortic isthmus diameter (β = 0.909, p = 0.001) had predictive value for ADAMTS13 activity. The Reynolds number predicted vWF/ADAMTS13 ratio (β = -0.529, p = 0.024). Plt/vWF made it possible to predict Vi over 56 μm/min (AUC = 0.810 (95 % CI 0.605–1.014), p = 0.003, cut-off = 6.44).

Conclusion. ADAMTS13 activity increases with increasing shear stress, and the dynamics of fibrin formation depends on vWF activity. In the state of the vWF/ADAMTS13 system, two variants can be distinguished, characterized by an increase in inhibitor activity and its depletion with an increase in vWF activity. The Plt/vWF ratio makes it possible to predict the occurrence of prothrombotic states in patients with obstructive forms of CHD, which in turn, makes it possible to recommend monitoring this ratio in children who are in their first few months of life.

Introduction. The use of invasive methods for diagnosing primary diffuse large B-cell lymphoma of the central nervous system (PDLBCL CNS) and primary vitreoretinal lymphoma (PVRL) is often associated with the development of severe neurological deficits and disability of patients. A promising direction in the diagnosis of PDLBCL CNS and PVRL is the use of non-invasive approaches based on molecular genetic methods for the determination of mutations in the MYD88 gene in the cerebrospinal fluid (CSF), vitreous fluid (VF) and free circulating tumor DNA (cfDNA) in blood serum.

Aim: to present the potential of non-invasive diagnosis of PDLBCL CNS and PVRL.

Main findings. The study included 6 patients (4 — PDLBCL CNS, 2 — PVRL). The average age was 64 (54–75) years. Despite increased cytosis in the CSF in all 4 patients with PDLBCL CNS, the tumor population was determined by flow cytometry in only half of the cases. According to a molecular genetic study, mutations in the MYD88 gene with an allelic load from 2.5% to 15% were detected in the genomic DNA of the CSF of all patients. In 2 patients with PVRL, mutations in the MYD88 gene were detected in VF with an allelic load of 4.2% and 6.6%, which was the only confirmation of the diagnosis. Currently, 5 patients have completed the treatment program and 1 is undergoing therapy. All 5 patients are in complete remission (CR) of the disease with follow-up periods from 1 to 8 months.