Histiocytic cell tumors present as a difficult group of diseases in terms of differential diagnosis due to their rare frequency, heterogeneous clinical manifestations and ambiguous clinical course. Considering MAPK-signaling pathway mutations role (including BRAFV600E) in the pathogenesis of histiocytic cell tumors the importance of genetic studies in the diagnosis and choice of therapeutic strategy in these diseases increases. In the current issue modern classifications of histiocytic cell tumors, morphological and immunophenotypic features of histiocytic and dendritic cells, and the role of recurrent somatic mutations of the MAPK signaling pathway in the pathological histiocytic proliferation are presented. Particular attention is given to Langerhans cell histiocytosis, Erdheim–Chester disease and juvenile xanthogranuloma. Clinical and diagnostic characteristics of these diseases and therapeutic approaches are presented.

Background. Over the past 15 years, the therapeutic breakthrough in the treatment of multiple myeloma observed primarily due to the emergence of new drugs. Since the characteristic of the disease is a chronic course with consecutive periods of remissions and relapses, the search for new effective treatment options with each subsequent relapse/progression is critical to increasing the survival of patients.

Objective: to evaluate the role of pomalidomide in the treatment of relapsed/refractory multiple myeloma.

Materials and methods. The results’ analysis of using pomalidomide-based treatment (Pd (pomalidomide/dexamethasone), PVd (pomalidomide/bortezomib/dexamethasone), KPd (carfilzomib/pomalidomide/dexamethasone), IxaPd (ixazomib/pomalidomide/dexamethasone), DaraPd (daratumumab/pomalidomide/dexamethasone), IsaPd (isatuximab/ pomalidomide/dexamethasone), EloPd (elotuzumab/pomalidomide/dexamethasone)) in pretreated patients, including own data, was done. Based on the RosNIIGT FMBA of Russia, 17 patients with relapsed/refractory multiple myeloma were treated; the frequency of achieving a response and the development of adverse events was estimated; the possibility of pomalidomide dose reducing with the development of adverse events was described without an apparent decrease of effectiveness.

Results. The frequency of the overall response in using pomalidomide-based programs was 53 % (according to the world data, from 38 to 82 %). This drug is recommended for patients with multiple myeloma, even accompanied by the final stages of renal failure. The most frequent adverse event was grade III–IV neutropenia (30 % of patients). In 3 patients, the dosage of pomalidomide was adjusted with a decrease to 2 mg per day. In 2 patients, therapy was discontinued due to pulmonary embolism and bilateral pneumonia. After three courses of DaraPd, one patient achieved a complete response and underwent autologous hematopoietic stem cell transplantation.

Conclusion. Pomalidomide-based programs in patients with relapsed/refractory multiple myeloma are an effective treatment option. Using dose-adjusted pomalidomide after the occurrence of neutropenia makes it possible to normalize the neutrophils level (more than 1 × 109/l) and continue anti-myeloma therapy, preserving the therapeutic effect and in individual patients with unfavorable prognosis factors to conduct high-dose therapy followed by autologous hematopoietic stem cell transplantation.

Background. The treatment results of patients with diffuse large B-cell lymphoma (DLBCL) with c-MYC proto-oncogene and BCL2 protein positivity according to the CHOP-21 ± R scheme remain unsatisfactory, which dictates the need to intensify the therapy regimen. Due to the fact that most authors combine DH (double hit) lymphomas and DE (double expressor) lymphomas for analysis, these data do not allow forming an accurate idea of the independent significance of the phenomenon of activated transcription factor c-MYC and BCL2 protein in patients with DLBCL and the results of treatment specifically in this group. Some researchers believe that the presence of c-MYC gene aberration and BCL2 protein expression are associated with negative clinical characteristics. Nevertheless, the clinical features of this subgroup of DLBCL remain poorly understood.

The objective of the study was to analyze the incidence of c-MYC gene aberrations, BCL2 expression in DLBCL patients and to evaluate the effectiveness of intensive R + Hyper-CVAD chemotherapy regimen in this group of patients.

Materials and methods. We analyzed the data of 80 patients aged 18–65 years with a newly diagnosed DLBCL for the period from 2018 to 2020. The diagnosis was established by histological and immunohistochemical examination. The tumor stages (II–IV) were assessed according to the Ann Arbor classification; the patient’s somatic status – according to the ECOG scale with a total of no more than 3 points. To detect c-MYC gene aberrations in the tumor tissue, fluorescent in situ hybridization was performed; to determine the BCL2 protein expression and Ki-67 proliferative index – an immunohistochemical study was performed. Patients with identified c-MYC gene aberrations received treatment, which included 8 courses of polychemotherapy according to the R + Hyper-CVAD scheme and high-dose chemotherapy according to the BFR scheme with autologous hematopoietic stem cell transplantation. Patients with DLBCL, in whom c-MYC gene aberration was not detected, were assigned to the group of intermediate and low malignancy. They received a polychemotherapy regimen according to the R-CHOP-21 scheme (up to 8 courses).

Results and conclusion. For the first time in Kazakhstan, we studied the incidence of c-MYC proto-oncogene aberrations, BCL2 protein expression and proliferative activity (Ki-67) in DLBCL patients, which made it possible to identify groups of highly aggressive tumor and intermediate, low malignancy, apply personalized polychemotherapy programs and evaluate the immediate treatment efficacy. This approach made it possible to increase treatment effectiveness in the group of patients with highly aggressive DLBCL and to achieve comparable results with therapy in patients with a more favorable prognosis.

Histiocytic tumors are a highly heterogeneous group of diseases, with Langerhans cell histiocytosis occupying the main place among it. Despite the rare frequency of occurrence, long-term analysis of clinical, morpho-immunological and molecular-biological features has allowed the development of effective treatment protocols (especially in the pediatric cohort of patients). In addition to Langerhans cell histiocytosis, the histiocytic tumors group includes rare and casuistic variants, which include histiocytic sarcoma, Langerhans cell sarcoma, indeterminate dendritic cell tumor, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, and fibroblastic reticular cell tumor. The incidence of certain nosological variants is several cases per hundreds of millions of the population. Not surprisingly, the diagnostic criteria for this group of tumors need to be clarified, as do the therapeutic approaches. This review presents current data on rare histiocytic tumors, clinical features as well as morphological and immunobiological characteristics of the tumor substrate. The results of modern surgical and therapeutic treatment approaches are presented.

Cutaneous T-cell lymphomas are a heterogeneous group of T-cell lymphoproliferative diseases affecting the skin. Mycosis fungoides and Sezary syndrome are the most studied variants of them. The literature review includes the latest published data on the pathological processes development in mycosis fungoides and Sezary syndrome and the diagnosis of these diseases. The genomic instability features in cutaneous T-cell lymphomas are described, the existing hypotheses of the origin of these diseases are considered based on the results of T-cell receptor repertoire studying.

This article describes the laboratory diagnostics stages of acute erythroid leukemia clinical case. The following research results allow observing the process of disease formation in development.

Idiopathic pulmonary hemosiderosis is a rare and severe disease in childhood with a poor prognosis. The main clinical symptoms are a combination of severe hypochromic iron deficiency anemia with severe recurrent pneumonia. The development of a hemolytic component with a moderate increase in indirect bilirubin and enhanced bone marrow erythropoiesis is possible. The disease is close to Goodpasture’s syndrome, in which the formation of antibodies to the basement capillaries membrane of not only the lungs, but also the kidneys has been proven. In the given clinical cases, notes an isolated lesion of lungs capillaries. The disease severity in these children was of varying degrees, but the prognosis is poor due to the progression of fibrotic changes in the lung tissue.

Magnetic resonance imaging (MRI) is increasingly being used to diagnose bone marrow lesions in patients with multiple myeloma (MM). Since 2014, the results of MRI have been included in the updated criteria of the International Myeloma Working Group. The presence of >1 bone marrow lesion larger than or equal to 5 mm on MRI is considered sufficient for the diagnosis of symptomatic MM, requiring initiation of treatment. MRI assessment of bone marrow is also possible with functional sequences such as diffusion-weighted imaging (DWI), which provide additional information about the bone marrow. This article provides an overview of the possibilities of MRI with anatomical sequences and with DWI for diagnosing, monitoring and evaluating the response to treatment in patients with MM. In patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, in some cases, pathological changes in the bone marrow can be detected by MRI. The presence of >1 bone marrow lesion on MRI is a cut-off value as a prognostic factor for the progression of monoclonal gammopathy of undetermined significance or smoldering myeloma to symptomatic MM. In symptomatic MM, there are four patterns of bone marrow infiltration on MRI – focal, diffuse, “salt-and-pepper” infiltration, and combined diffuse and focal pattern, which have prognostic significance. Patients with diffuse pattern of infiltration on MRI had a 3-year overall survival of 35 % versus 92 % in patients with normal MRI bone marrow. During treatment of MM patients, residual bone marrow lesions are often identified on MRI. MRI residual bone marrow lesions increase the risk of MM relapse. In the group of patients who had residual bone marrow lesions on MRI on the 100th day after autologous hematopoietic stem cell transplant, 2-year progression-free survival was 50 % versus 89 % in patients without bone marrow lesions at the same time. The addition of DWI to the scan protocol helps to differentiate persistent focal bone marrow lesions that can lead to MM relapse after the treatment phase. Apparent diffusion coefficient is a quantitative indicator of DWI. MRI can serve as a valuable tool for assessing the treatment response in patients with MM.

Objective: to evaluate the possibilities of strain elastography (SE) in eSie Touch mode and shear wave elastography (SWE) with ARFI (Acoustic Radiation Force Impulse) technology in Virtual TouchTM Tissue Imaging (VTI) for diagnostics lymphomatous superficial lymph nodes (LN).

Materials and methods. The prospective study included 168 patients with enlarged superficial LN. Based on a previous histological examination, patients were divided into three groups: group 1 (n = 108) – patients with lymphomas; group 2 (n = 30) – patients with metastatic superficial LN; group 3 (n = 30) – patients with reactive (inflammatory) changes in superficial LN. All patients underwent SE and SWE elastography of the enlarged LN using eSie Touch and VTI modes respectively.

Results. The SE data: reactive LN was characterized by elastotypes 1 and 2 with a predominance of elastic structure in 90.0 % of cases. In patients with lymphomas, the elastotype 3 was more often determined (58.3 %). The stiffest LN with the elastotype 4 were metastatic LN, detected in 66.7 % of patients from this group. The results of VTI elastography showed that the stiffest structure is typical for metastatic LN (elastotypes 5–6 in 63.3 % of cases). Lymphomas had an intermediate degree of stiffness (elastotypes 3–4 in 81.5 % of cases). The lowest indicators of elasticity were found in patients with reactive LN (elastotypes 1–2 in 73.4 % of cases).

Conclusion. The qualitative assessment of superficial LN stiffness, both using SE and VTI elastography, demonstrated statistically significant differences in the frequency of various types of superficial LN elastograms with lymphomatous, metastatic and reactive changes, which allows for more accurate differential diagnosis between these types of lymphadenopathy.

The objective of the study was to determine the clinical and morphological criteria and prognostic significance of CD163- and CD68-expressing macrophages in formalin-fixed paraffin-embedded (FFPE) lymph node samples of nodular sclerosis Hodgkin lymphoma.

Materials and methods. We have studied clinical and laboratory characteristics and treatment results of 52 patients with newly diagnosed nodular sclerosis Hodgkin lymphoma. The treatment efficacy was assessed after 2–4 courses of chemotherapy by positron emission tomography combined with computed tomography scan (PET-CT) according to the Deauville scale.

Results. In FFPE lymph node samples, differences in the localization and relative number of CD163-positive macrophages in patients of both study groups were determined. Morphometric counting of CD68-positive cells did not reveal statistically significant intergroup differences. The threshold of CD163-positive cells has been established. The relationship between the CD68 expression level and the response to frontline therapy was not revealed. The ratio of tumorassociated macrophages in each patient was assessed by the CD163/CD68 index. The threshold of the index was determined, which allows predicting the course of nodular sclerosis Hodgkin lymphoma.

Conclusion. The following parameters could be used as additional morphological criteria for predicting the response to frontline therapy in patients with nodular sclerosis Hodgkin lymphoma: tissue distribution pattern and quantitative calculation of macrophage-histiocytic microenvironment subpopulation composition. The results could be used to risk group stratification of patients with nodular sclerosis Hodgkin lymphoma in order to predict the response to initial phase of therapy, as well as to determine personalized treatment approaches.

Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome occurring with a frequency of 1: 3000 of the population. NF1 is caused by germline heterozygous mutations in the NF1 gene, which encodes the oncosuppressor neurofibromin. The disease has a specific progressive course with multiple neurofibromas, in the initiation and growth of which NF1^{+/ –} mast cells, macrophages and lymphocytes play an important role. Accordingly, the deficiency of neurofibromin impairs the differentiation and correct functioning of immune system cells. This is evidenced by the increased risk of leukemia in patients with NF1 and the role of NF1 mutations in the development of sporadic hematological malignancies. The development of neurofibromas is associated with the fact that NF1^{–/ –} Schwann cells stimulate the migration of mast cells into the tumor microenvironment, which actively degranulate. The released cytokines promote neoangiogenesis, inflammation, fibroblast proliferation and the production of excess collagen. Therefore, in the treatment of NF1, the use of ketotifen and a kit/ fms kinase inhibitor is recommended. Macrophages and T-lymphocytes in neurofibromas do not provide an antitumor response, but promote inflammation and tumor growth. They produce STAT3 (signal transducer and activator of transcription 3), TGF-β, EGFR, IL-6, IL-4, and PD-1. Therefore, a promising direction is NF1 therapy with STAT3 inhibitors and immune checkpoint inhibitors that block programmed cell death ligand 1 (PD-L1). Activation of MEK signaling pathways in NF1 leads to PD-L1 stimulation; therefore, MEK inhibitors, which also suppress the RAS/RAF/MEK/ERK system, turned out to be effective in the treatment of NF1. For the treatment of sporadic malignant neoplasms, in the development of which NF1 mutations play a role, the developed methods of NF1 therapy can be used.

Background. Bloodstream infections (BSI) are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The objective of study was to analyze pre- and post-engraftment BSI.

Materials and methods. From January 2018 till May 2021242 patients after first allo-HSCT were enrolled in the study. Median age was 35 (17–65) years. The majority of transplants were done for acute leukemias (71.9 %) in remission (91.7 %) with reduced-intensity conditioning regimens (71.5 %) and peripheral blood stem cells (74.4 %) as a graft source.

Results. Of 242 patients 95 (39.2 %) developed BSI: 79 (83.2 %) developed 1 BSI episode, 16 (16.8 %) – 2 or more. Overall 113 BSI episodes were registered: 94 (82.7 %) were caused by single microorganism, 19 (17.3 %) were polymicrobial. Probability of pre-engraftment BSI was 31.0 %, post-engraftment – 11.8 %. In total 134 microorganisms were identified: 61.2 % – gram-negative and 38.8 % – gram-positive bacteria. Gram-negative BSI rate was significantly higher during post-engraftment compared to pre-engraftment phase (57.7 % vs. 70.3 %; р = 0.008). Major risk factor for pre-engraftment BSI was mismatched unrelated allo-HSCTs (hazard ratio (HR) 2.55; 95 % confidence interval (CI) 1.32–4.91; р = 0.03), for post-engraftment BSI – secondary poor graft function (HR 21.70; 95 % CI 7.95–59.24; р <0.0001) and graft failure (HR 21.55; 95 % CI 6.27–74.08; р <0.0001), and gut graft-versus-host disease (HR 12.90; 95 % CI 5.77–28.80; р <0.0001). Thirty-day survival after each BSI episode was 90.3 % and was significantly lower in patients with post-engraftment BSI compared to pre-engraftment (71.9 % vs. 97.5 %; р <0.0001).

Conclusion. Gram-negative bacteria prevailed in the etiology of BSI. The main risk factors for pre-engraftment BSI was allo-HSCT from mismatched unrelated donors, for post-engraftment BSI – secondary poor graft function and graft failure. Post-engraftment BSI is associated with worse prognosis.

Neutropenia is the most common hematologic toxicity of chemotherapy. Severe and prolonged neutropenia can cause treatment delay and dose reduction. Clinical studies indicate that reducing the relative dose intensity of regimens harms treatment outcomes, especially in breast, ovarian, and pancreatic cancers. Therefore, screening of patients at high risk of neutropenia that limits planned chemotherapy is of practical importance. Unfortunately, most clinical studies indicate only the incidence of myelotoxicity with each chemotherapy regimen, and only a few have analyzed the potential risks associated with this complication. That is significant importance in highly chemotherapy-sensitive malignancies. Such patients often receive dose intense and dose dens chemotherapy. The risk of severe neutropenia in such patients and failure to adhere to planned chemotherapy may reduce the chances of cure. Currently, there is no consensus among oncologists on the management strategy for patients with neutropenia limiting chemotherapy. This topic is a worldwide discussion. The article presents scientific evidence and clinical studies dedicated to this problem. A general analysis of clinical data and experience of oncologists will allow the medical community to develop approaches to prevent this complication.