Background. Information on the epidemiological picture of chronic myeloid leukemia (CML) and, especially, Ph^– chronic myeloproliferative neoplasm (MPN) in Russia is very scarce, each regional population study is important for obtaining information on the diseases in general.

Aim. To analyze the regional epidemiological parameters of the most common MPN over a long period of time (2012–2023).

Materials and methods. Clinical and epidemiological, population, retrospective-prospective, observational study of CML and classical Ph^– MPN (polycythemia vera, essential thrombocythemia, primary myelofibrosis) was conducted at the Moscow City Hematology Center, Botkin Hospital. The observation period was from January 1, 2012 to December 31, 2023. The research database included data from the medical records of regional patients (Moscow).

Results. At the time of analysis, the database contained 2191 patients with CML and 5831 with Ph^– MPN observed since 2000. In both cohorts, women prevailed with a ratio of 1:1.1 for CML and 1:1.6 for Ph^– MPN. The median age of patients in the overall cohort since 2000 at diagnosis of CML was 55 years (men – 52, women – 57), and of Ph^– MPN – 64 years (men – 62, women – 64). During the study period, an increase in the median age and in the proportion of diagnosed CML patients aged 65 years and older were noted, the same was not observed in Ph^– MPN. However, an increase in the median age and the proportion of elderly patients was revealed in both general cohorts of CML and Ph^– MPN. The registered prevalence of CML and Ph^– MPN over a 12-year period increased by 90 % (from 6.0 to 11.4 cases per 100,000 population) and 93 % (from 15.28 to 29.46 cases per 100,000 population), respectively. The high reliability of linear trends indicates a uniform increase in the prevalence of CML and Ph^– MPN. The registered annual incidence rate of CML increased over 12 years from 0.74 to 1.13 cases per 100,000 population, and Ph^– MPN – from 2.05 to 2.84. An increasing tendency in registered annual mortality from 0.23 to 0.36 per 100,000 population for CML, from 0.87 to 1.04 per 100,000 population for Ph^– MPN was observed. Its maximum rates in both cohorts matched with the COVID-19 pandemia period; for Ph^– MPN the increase was more pronounced. All over the investigated period, the registered annual morbidity rate always exceeded the registered annual mortality rate. In general, the pandemic did not have a significant impact on the registered epidemiological parameters of both cohorts. In the total CML group, 2-, 5-, 10-year overall survival (OS) was 91, 82, 68 %, in Ph^– MPN – 93, 83, 63 %, respectively; the median OS was not achieved in both cohorts. The 5- and 10-year OS for Ph^– MPN differed between male and female cohorts: 86 and 67 % versus 79 and 58 %, respectively (p <0.05). In younger (younger than 65 years) patients, 5- and 10-year OS were higher (p <0.001) than in patients aged 65 years and older: 89 and 80 % versus 63 and 35 % in CML, 92 and 80 % versus 73 and 44 % in Ph^– MPN, respectively. The median OS in CML and Ph^– MPN was not achieved in patients younger than 65 years, and among older patients it was 90 months in CML and 105 months in Ph^– MPN.

Conclusion. An assessment of CML and Ph^– MPN epidemiological indicators dynamics over a 12-year period made it possible to draw a number of conclusions about the population characteristics of each studied cohorts and to identify similar trends and differences in the changes occuring.

Backround. Mastocytosis is a rare disease characterized by pathological accumulation of mast cells in one or more organs. According to the world Health Organization classification (2016), a monomorphic type of maculopapular cutaneous mastocytosis (monoMPCM) was identified among cutaneous clinical forms. In adolescents with monoMPCM (the “adult” type pattern), clinical manifestations persist into adulthood and can transform into a systemic process, so interdisciplinary monitoring of these patients is necessary.

Aim. To analyze the clinical and laboratory features of the monomorphic type of MPCM in children and adolescents.

Materials and methods. The study included data from 66 patients with monoMPCM who were undergoing outpatient treatment and observation at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology. All patients underwent clinical, laboratory (basal serum tryptase), molecular (c-KIT gene mutation in exons 8–11, 17 by polymerase chain reaction), instrumental (ultrasound) examination of the abdominal organs and mesenteric lymph nodes. The serum interleukin 6 concentration was determined by flow cytometry using the ProcartaPlex™ Human Panel 1A Cytokine & Chemokine 34 plex multiplex analysis kit (eBioscience, Austria).

Results. The median age of disease onset was 4 [3; 7] years (minimum age – 2 years, maximum – 16 years). The median value of basal serum tryptase was 10.9 (2.84–46.3) μg/L, among adolescents – 14 [10.8; 23.7] μg/L. Hepatosplenomegaly and enlarged mesenteric lymph nodes (mesadenitis) were diagnosed in 14 (21.2 %) patients with monoMPCM. The serum interleukin 6 concentration in patients with organomegaly was 10.1 [9.28; 25.5] pg/mL, which exceeded the reference values by 2.4 times. The KIT d816v mutation was detected in 3 (11.5 %) patients out of 26 examined patients with monoMPCM.

Conclusion. The modern course of cutaneous mastocytosis demonstrates a tendency towards an increase in the number of cases and a more severe disease course in children. Particular attention should be paid to adolescents with monoMPCM and organomegaly, high serum tryptase levels and identified KIT d816v mutations in the peripheral blood as a risk group for the development of a systemic process.

Background. Mastocytosis is a group of diseases characterized by tumor proliferation of mast cells and their accumulation in organs and tissues, including skin, hematopoietic organs (bone marrow, spleen, lymph nodes), and the gastrointestinal tract, which is clinically manifested by symptoms of mast cell activation and organ infiltration in the form of hepatosplenomegaly, portal hypertension, ascites, and cytopenia. Of the greatest scientific and clinical interest is systemic mastocytosis (SM), where indolent (indolent SM, smoldering SM, SM with isolated bone marrow involvement) and advanced forms (aggressive SM, SM with associated hematological neoplasm and mast cell leukemia) are distinguished. The SM clinical course is extremely heterogeneous and diverse. Patients differ significantly from each other both in clinical manifestations and in the aggressiveness of the disease. Currently, there are no clear pathogenetic explanations for such a variety of clinical manifestations. More than 80 % of SM patients have the KITD816V mutation, and more than 50 other mutations in the KIT gene have been described. Additional mutations not associated with the KIT gene are being identified, which likely determine the SM clinical diversity. One of the directions that may help to understand the SM heterogeneity is an extended study of SM genetic characteristics using next-generation sequencing (NGS).

Aim. To study the genetic features and differences between indolent and advanced SM forms.

Materials and methods. The data of 27 SM patients (11 (41 %) men and 16 (59 %) women), observed at the Moscow City Hematology Center of the Botkin’s Hospital, were analyzed. The patients were divided into 2 groups: group 1 – patients with advanced SM variants, group 2 – patients with indolent SM variants. NGS was performed in all patients using the Illumina Myeloid Panel, which includes 40 genes.

Results. As a result of the NGS study of 27 patients, mutations of unfavorable clinical significance were found in 18 genes: CBL, CALR, JAK2, MPL, ASXL1, EZH2, NF1, SETBP1, DNMT3A, SF3B1, SRSF2, ABL1, RUNX, SH2B3, STAG2, TET2, KIT, PHF6. The frequency of additional mutations (non-driver) in the total group was as follows: TET2 – 37 %, SRSF2 – 22 %, DNMT3A/STAG2 – 19 % each, CBL – 11 %, SF3B1/NF1/PHF6 – 7 % each, ASXL1/EZH2/RUNX/SH2B3/ABL1 – 3.5 % each. In group 1 additional mutations of unfavorable clinical significance were detected in 13 (93 %) of 14 patients. In group 2 additional mutations of unfavorable clinical significance were detected in only 3 (23 %) of 13 patients. No additional mutations of adverse clinical significance were found in any of patients with indolent SM variants.

Conclusion. The results of this study suggest that additional mutations of unfavorable clinical significance determine a more aggressive SM course. In patients with SM, NGS helps in diagnosis and prognosis of the disease course.

Background. The most common mechanism of resistance to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML) is point mutations in the BCR::ABL1 gene. Of particular importance is the T315I mutation, which causes insensitivity of leukemia cells to all ATp-competitive TKIs: imatinib and 2^nd generation TKIs. Asciminib is the first drug of the STAMp inhibitor class that specifically interacts with the myristoyl-binding active site of the bCR::AbL1 molecule. In a phase I clinical trial, asciminib at a dose of 200 mg twice daily showed efficacy in the treatment of chronic phase (Cp) CML patients with T315I mutation. There are no data on the efficacy of asciminib therapy in patients with T315I mutation and additional chromosomal abnormalities (ACA) or advanced disease. The Russian part of the managed access program (MAp) has accumulated its own experience of using asciminib in CML patients with T315I mutation, including those with ACA and history of progression to the acceleration phase / blast crisis.

Aim. To analyze the 3-year results of asciminib therapy as part of MAp in CML patients with T315I mutation.

Materials and methods. In the MAp program to asciminib between October 2019 and January 2022 were included 26 CML patients with T315I mutation who were ineffective or intolerant to ATp-competitive TKIs therapy. Asciminib was administered at a dose of 200 mg twice daily. The efficacy and tolerability of asciminib therapy were assessed in accordance with national clinical guidelines and the 2020 European LeukemiaNet guidelines.

At the time of asciminib therapy initiation, 19 (73 %) patients had Cp. four (15 %) patients had a history of acceleration phase (n = 3) and blast crisis (n = 1). four (15 %) patients had ACA immediately before the start of asciminib therapy, including a patient with a history of blast crisis. To analyze the asciminib therapy results, patients with a history of progression and / or ACA were combined into one group: 2Cp / Cp ^ACA+ (n = 7). More than half of patients (54 %) had previously received ponatinib.

Results. The median duration of asciminib therapy was 31.6 (3.3–50) months. Of the 26 patients, 25 (96 %) are alive, one patient in the 2Cp / Cp ^ACA+ group died from progression of CML to myeloid blast crisis. In the total group, 14 patients (54 %) continued asciminib therapy, 12 (46 %) – discontinued treatment: most patients due to treatment failure (n = 9 (75 %)). In 3 patients (25 %), the reason for treatment discontinuation was allogeneic hematopoietic stem cell transplantation (all three achieved a complete cytogenetic response with asciminib therapy). No patients discontinued treatment due to toxicity. No new mutations, including asciminib resistance mutations, were detected during therapy.

Progression-free survival and survival without therapy discontinuation at 3 years of follow-up in the total group were 92 and 58 %, respectively. when analyzing the Cp and 2Cp / Cp ^ACA+ groups, progression-free survival at 3 years of asciminib therapy was comparable. There was a trend toward decreased survival without therapy discontinuation in 2Cp / Cp ^ACA+ group (28 %) versus Cp group (63 %) (p = 0.0856).

The probability of achieving a complete cytogenetic response / molecular response MR2 in all patients with T315I mutation by the 3^rd year of asciminib treatment was 59 %, in the Cp and 2Cp / Cp ^ACA+ groups – 47 and 80 %, respectively; no significant difference were found between the groups (p = 0.08). The probability of achieving a major molecular response (MMR) in the total group by the 3^rd year of asciminib treatment was 42 %; the probability of achieving MMR in the Cp and 2Cp / Cp ^ACA+ groups was 44 and 33 %, respectively; no significant difference were found between the groups (p = 0.6).

In univariate analysis, significant favorable factors for achieving MMR were the molecular response at the start of asciminib therapy ≤10 %, the best molecular response in prior TKI therapy ≤1 %, and the absence of prior ponatinib treatment. In multivariate analysis, a history of ponatinib therapy was an independent significant factor for achieving MMR with asciminib therapy (p = 0.02; hazard ratio 12.08).

Conclusion. The therapy results of patients in initially unfavorable 2Cp / Cp ^ACA+ group were comparable with Cp group in terms of both survival rates and probability of achieving responses. However, given the small number of patients in our cohort, the asciminib efficacy in patients with T315I⁺ CML with ACA and a history of progression requires further investigation. A factor that significantly reduced the probability of achieving MMR during asciminib treatment was a history of ponatinib therapy.

Acute lymphoblastic leukemia (ALL) manifested by eosinophilia (>1.5 × 10⁹/L) in peripheral blood is extremely rare, less than 1 % of all ALL cases. A characteristic feature of patients with ALL and eosinophilia is the absence of blasts in the peripheral blood, which can make early diagnosis of ALL difficult. The article describes the clinical case of 2-year-old patient with ALL and eosinophilia. due to the wide variety of etiologic factors of eosinophilia, which include allergic, infectious, immune agents, and a high risk of developing severe lesions of internal organs, physicians should conduct a broad differential diagnosis with the mandatory inclusion of malignant neoplasms in the diagnostic series. precise determination of the etiology of eosinophilia allows the correct diagnosis and etiotropic treatment.

Cytogenetic studies are required for the diagnosis of myelodysplastic neoplasms (MDS) because the World Health Organization 2022 classification divides MDS into a group with defined genetic abnormalities and MDS that are defined morphologically. Additionally, this paper modifies the terminology to clarify the distinction between MDS with low (<5 % in bone marrow) and increased blast cell counts (5–9 % for MDS with blast excess 1 and 10–19 % for MDS with blast excess 2).

This article describes the clinical observation of a patient with blast excess MDS and isolated 5q deletion.

Background. Glucocorticoids are widely used in the treatment of acute lymphoblastic leukemia. However, antileukemic effects are often accompanied by the development of serious metabolic and atrophic complications. A safer alternative may be drugs of the class of selective glucocorticoid receptor agonists with a more favorable safety profile.
Aim. To evaluate the effects of new selective glucocorticoid receptor agonists of the synephrine derivative class in vitro on bone marrow blasts of patients with acute lymphoblastic leukemia and compare the results with the clinical response to therapy.
Materials and methods. Bone marrow blasts of patients with acute lymphoblastic leukemia were isolated in a ficollurographin gradient. The proportion of viable cells was assessed using a resazurin test. The expression of specific glucocorticoid response marker genes was assessed using quantitative polymerase chain reaction. Therapeutic treatment response was assessed according to ALL IC-BFM 2009 protocol on 8, 15 and 33 days.
Results. IC50 values of novel selective glucocorticoid receptor agonists 10S-E2 and 13S-G2 were calculated with blasts death level in 50 %. The effects of the most cytotoxic compound 10S-E2 on the expression of glucocorticoid-regulated genes (FKBP51 and COX2), were evaluated and compared with clinical response to treatment.
Conclusion. The sensitivity of bone marrow leukemic blast cells to the 10S-E2 compound in vitro correlates with the clinical response of patients to glucocorticoid therapy, which suggests a good clinical response to therapy with potential drugs of selective glucocorticoid receptor agonists class.

In recent years, microRNAs have attracted the attention of researchers as potential markers for diagnosis, classification, prognosis of tumor progression and sensitivity to treatment, as well as their use as targets for therapy. The purpose of the review is to summarize data on the miR-142 role in the tumor progression of one of the most common lymphoproliferative diseases – diffuse large B-cell lymphoma.
MicroRNA miR-142 has a broad spectrum of tumor-suppressor functions by targeting a number of important protooncogenes, the loss of control over which contributes to enhanced proliferation, blocking apoptosis, activating B-lymphocyte survival signaling pathways, metabolic reprogramming, creating an immunosuppressive microenvironment and tumor evasion of immune surveillance, as well as dissemination of malignant cells.
Information on the nomenclature and mechanisms of miR-142 formation, the participation of miR-142 in hematopoiesis are provided, the pathogenetic role and relationship between the miR-142 expression profile and diffuse large B-cell lymphoma are analyzed, and miR-142 molecular genetic abnormalities in this disease are discussed.

Waldenstrom’s macroglobulinemia (WM) is a subtype of lymphoplasmacytic lymphoma that combines lymphoplasmacytic lymphoma substrate in the bone marrow and monoclonal immunoglobulin M secretion in the blood. WM diagnosis is a complex process, which is due to both the heterogeneity of tumor populations and similarity to other B-cell lymphomas. The WM tumor cell clone has unique immunophenotypic characteristics and is represented by two aberrant populations from one tumor clone: clonal B-lymphocytes and plasma cells. Detection and characterization of these two aberrant populations seems possible only using multicolor flow cytometry. Bone marrow cell immunophenotyping by flow cytometry establishes the tumor cell immunophenotype, which plays a key role in the differential diagnosis of WM from other types of small cell lymphomas, as well as when other methods are uninformative.
To assess the depth of therapy response, instrumental and laboratory methods are used, including positron emission tomography combined with computed tomography to monitor the size and spread of the tumor mass, immunochemical testing to measure the monoclonal immunoglobulin M secretion, molecular bone marrow research for the presence of MYD88 gene mutations, as well as bone marrow cell immunophenotyping by multicolor flow cytometry. Currently, it is especially important to study the dynamics of minimal residual disease in WM using the capabilities of multicolor flow cytometry.

Despite significant advancements in antiretroviral therapy, HIV viral reservoirs continue to persist even in patients receiving combination therapy. In recent years, promising results have emerged in HIV treatment, including two cases of functional cure known as the “Berlin patient” and the “London patient”, both of whom received allogeneic hematopoietic stem cell transplants from donors with the CCR5Δ32 mutation. These cases underscore the importance of genetically modified stem cells in achieving resistance to HIV. The development of genome editing methods, such as CRISPR/Cas9, opens new horizons for creating targeted therapies aimed at eliminating the virus from infected cells. Research also shows promise in the application of cell immunotherapy, including CAR T-cells and NK cells, which may enhance control over HIV due to their ability to recognize and destroy infected cells. In light of these achievements, research in gene therapy targeting co-receptors, as well as new approaches such as virus activation and elimination methods, represents critical steps toward achieving a functional cure for HIV.
This review discusses progress in genetic manipulation, immunotherapy, and the adaptation of conditioning regimens to develop effective treatment strategies for a broad range of HIV patients.

The article discusses the epidemiology and difficulties of diagnosing invasive aspergillosis in patients with acute myeloid leukemia, the role of pharmacokinetic and pharmacogenetic studies in choosing the optimal treatment regimen, and an attempt at pharmacoeconomic analysis to create an optimal treatment strategy for this complication.

Backround. Treatment protocols for non-Hodgkin’s lymphomas in pediatric patients include a combination of cytotoxic drugs, with methotrexate (MTX) playing a central role, often administered in high doses (1000–5000 mg/m²). MTX is associated with a wide range of side effects, manifesting as organ toxicity (hemato-, hepato-, neuro-, nephrotoxicity, mucositis, infectious complications). Neurotoxicity poses a significant challenge in real clinical practice. The pathogenesis of neurological complications is not fully understood, making investigations into potential predictive factors for neurotoxicity development, as well as methods for its prevention and treatment, highly relevant.

Aim. To analyze clinical, laboratory and instrumental data in the development of MTX-induced neurotoxicity and to identify potential predictive factors.

Materials and methods. This study presents an analysis of literature data on MTX neurotoxicity and our own clinical cases of non-Hodgkin’s lymphomas patients who developed severe neurological complications following MTX- containing treatment regimens. Non-Hodgkin’s lymphoma diagnosis was verified according to the clinical guidelines of the Ministry of Health of the Russian Federation. Antitumor treatment and supportive care were administered according to B-NHL-BFM 95 or ACCL NII DOG-2003 protocols. The severity of toxicities was assessed using the National Cancer Institute (USA) Common Terminology Criteria for Adverse Events. All patients underwent genetic testing by allelespecific hybridization on a biological microarray. The study material was DNA extracted from peripheral blood lymphocytes. The timing of blood samples collection was not standardized.

Results. Neurological complications associated with high-dose MTX therapy can manifest as seizures, stroke-like symptoms, aphasia, and other neurological deficits. T2-weighted and FLAIR magnetic resonance imaging sequences reveal hyperintense signals in the white and gray matter of the brain. In the four presented clinical cases, neurological complications included Wernicke’s encephalopathy and encephalitis. Genetic testing in 3 patients revealed the heterozygous A allele of MTHFR rs1801133. In addition, one patient was found to have the heterozygous G allele of MTHFR rs1801131. All patients had the heterozygous G/A genotype in the SLC19A1 rs2838958 gene, and three patients had the heterozygous C/T genotype of SLC19A1 rs1051266. Heterozygous T/C genotype and homozygous C/C genotype were also identified for SLCO1B1 rs4149056.

Conclusion. The risk of neurotoxicity is determined by the pharmacological characteristics of MTX and, possibly, genetic factors. This study demonstrates that neurological complications during MTX-containing therapy are heterogeneous, often life-threatening, and require a multidisciplinary approach. The obtained data on genetic polymorphisms may become an effective tool in predicting the development of neurotoxicity.