Background. Extramedullary infiltration (EI) is relatively common in children with acute myeloid leukemia (AML) (up to 20-25 %). However, its clinical and prognostic significance remains poorly understood.

Objective: to describe clinical features and to define prognostic significance of EI in children with AML.

Materials and methods. The subjects of retrospective observational study were 228 children with de novo AML. The median age was 6.6 years. All of them were treated according to the protocol AML-MM-2006 from April 2007 to June 2018.

All patients with EI were divided into three cohorts according to the localization of the lesions: 1) central nervous system (CNS) involvement (CNS group), 2) other localizations apart from CNS (myelosarcomas (MS) group), 3) combined lesions (CNS + MS group).

Results. EI was diagnosed in 84 patients (36.84 %) with de novo AML. Among them 47 (55.95 %) had CNS involvement, 20 (23.81 %) had MS, 15 (17.86 %) had both CNS involvement and MS. 5-year overall survival (OS) rate was slightly higher in patients with CNS involvement than in children without EI - 80 ± 12 % vs 71 ± 9 %, p = 0.26, however OS in patients with MS was significantly lower - 45 ± 16 % vs 71 ± 9 %, p <0.001. In addition, OS in high-risk patients according to the protocol AML-MM-2006 who underwent allogenic hematopoietic stem cell transplantation (HSCT) without EI and with MS (± CNS involvement) was similar to OS in main groups - 81 ± 11 % and 42 ± 26 % respectively, p = 0.004. 5-year event-free survival in patients with MS was also lower than in children without EI - 38 ± 16 % vs 51 ± 8 %, p = 0.011.

Conclusion. Patients with MS had worse 5-year OS and EFS than children without EI according to our study. Moreover allogenic HSCT conducted in first clinical remission did not improve the survival rate. Neuroleukemia as the only EI was not an unfavorable prognostic factor in our cohort of AML patients and was more often associated with inv(16).

Telomeres are protein structures that regulate the process of cellular aging and play the role of a protective “cap” on the end sections of chromosomes. The telomeres of nucleated cells undergo permanent shortening during their lifetime as a result of multiple cycles of DNA replication. The enzyme that provides completion of the missing telomeric repeats at the ends of chromosomes is called “telomerase”. However, recovery of critically short telomeres by telomerase or recombination in somatic cells is limited due to the presence of a large accumulation of unclosed telomeres, which triggers apoptosis. The death of stem cells due to telomere depletion ensures the selection of abnormal cells in which the genome instability contributes to malignant progression. During carcinogenesis, cells acquire mechanisms for maintaining telomeres in order to avoid programmed death. In addition, tumor cells are able to support the telomere's DNA, counteracting its shortening and premature death. Activation of telomere length maintenance mechanisms is a hallmark of most types of cancers. In the modern world, there is an increasing interest in studying the biological characteristics of telomeres. The development of new methods for measuring telomere length has provided numerous studies to understand the relationship between telomere length of human nucleated cells and cancer. Perhaps maintaining telomere length will be an important step, determining the course and prognosis of the disease. The purpose of this review is to provide an analysis of published data of the role and significance of telomere length in patients with hematological malignancies.

Atypical hemolytic uremic syndrome is a rare disorder uncontrolled complement activation, which is classically manifested by anemia, thrombocytopenia and renal failure. Extrarenal manifestations are observed in 20 % of patients, most of which are associated with damage of the central nervous system. Eculizumab is effective treatment option. The article describes a case report of the severe atypical hemolytic uremic syndrome in a 20 m. o. patient who received immunotherapy with anti-GD2 antibodies (dinutuximab beta) for a high-risk neuroblastoma.

Background. Hemoblastoses treatment success in children made it possible to cure the vast majority of patients. The follow-up period exceeds tens of years, during which the problem of second tumors (ST) becomes urgent.  The objective of the study was to characterize ST in patients who underwent a malignant tumor of hematopoietic and lymphoid tissues at the age of 0 to 18 years.

Materials and methods. The study included 64 patients with ST development in the period from 1 to 38 years.

Results. Most frequently ST developed after treatment of Hodgkin's lymphoma (45.3 %) and acute lymphoblastic leukemia (35.9 %), supported by high cumulative doses of alkylating agents and radiation therapy. Among STs, in 35.9 % of cases, thyroid cancer was diagnosed, in 10.9 % - acute leukemia, in 9.4 % - tumors of the central nervous system.  The results of ST treatment are significantly worse than those of primary tumors. Thus, of 64 patients with ST, 46 (71.9 %) are alive, death from ST progression was noted in 18 (28.1 %) cases.

Conclusion. Improvement of modern treatment protocols aimed at reducing the indications for radiation therapy and cumulative doses of alkylating agents, along with the development of effective follow-up programs for children cured of hematological malignancies, will probably help reduce the ST incidence.

Background. In present days, much attention is paid to the study of the interrelation between the macrophage/hystiocytic microenvironment and the tumor substrate in lymphoproliferative disorders.

Objective. The article is devoted to the morphometric and morphological assessment of CD163-positive macrophages in nodular sclerosis Hodgkin lymphoma.

Materials and methods. Formalin fixed, paraffin-embedded (FFPE) lymph node samples of 45 patients were used for the study. To identify and visualize CD163-positive cells in the test material, an immunohistochemical staining method was used.

Results. The study shows that the morphometric and morphological analysis of CD163-positive cells can be an effective and promising criterion for representing them as potential predictors of the disease course. Immunohistochemical study of 45 cases using the CD163 marker revealed a difference in the nature of macrophages localization in the lymph nodes nodules. The dependence of CD163-expressing cells number on the disease course was determined.

Conclusion. The data obtained can be used to stratify patients with nodular sclerosis of classical Hodgkin lymphoma into risk groups and to determine personalized approaches to treatment. Immunohistochemical determination of the CD163 marker can be used in the complex diagnosis of the causes of refractoriness to the first and subsequent lines of therapy.

Objective: to determine antimicrobial resistance of Enterococcus faecium and Enterococcus faecalis isolated from blood culture of hematological patients during different study periods.

Materials and methods. Antimicrobial susceptibility of Enterococcus spp., collected as part of the multicenter study was tested by the broth microdilution method (USA Clinical and Laboratory Standards Institute (CLSI), 2018), to daptomycin by Etest (bioMeriéux, France). High-level gentamicin resistance (HLGR) and high-level streptomycin resistance (HLSR) was performed by the agar dilution method (CLSI (Oxoid, UK), 2018).

Results. The susceptibility of 366 E. faecium (157 in 2002-2009 and 209 in 2010-2017) and 86 E. faecalis (44 in 20022009 and 42 in 2010-2017) was studied. In the second study period (2010-2017) the rise of vancomycin-resistant E. faecium (VREF) increased from 8.3 % to 23.4 % (p = 0.0001), and two linezolid-resistant (LREF) were identified. All VREF and LREF remained susceptible to daptomycin and tigecycline. The rate of susceptible to tetracycline E. faecium remained the same (73.9 and 74.6 %), and an increase in susceptibility to chloramphenicol (74.5 and 82.3 %) was observed. Susceptibility of E. faecium to tetracycline was detected with almost the same rate and in a part of isolates, the increase of susceptibility to chloramphenicol was registered during the analyzed periods. The rise of E. faecium susceptible to HLGR and HLSR has increased significantly in 2010-2017 compared to 2002-2009. Erythromycin, levofloxacin, ampicillin and penicillin had the least activity against E. faecium (less than 5 %).

All E. faecalis were susceptible to tigecycline, linezolid, and teicoplanin. Only one of E. faecalis had intermediate resistance to vancomycin. High susceptibility to ampicillin in E. faecalis remained unchanged (97.7 and 97.6 %, respectively). In the second period of the study the rise of susceptible E. faecalis decreased significantly to penicillin (from 97.7 % to 76.2 %), to levofloxacin (from 59.1 % to 31 %), to HLSR (from 52.3 % до 31 %), and to HLGR (from 47.7 % to 26.2 %), remained unchanged to chloramphenicol (52.3 % and 50 %) and was minimal to erythromycin and tetracycline.

Conclusion. The study demonstrated higher rates of antibiotic resistance among E. faecium, which consisted of an increase in VREF and the appearance of linezolid-resistant strains. High susceptibility to ampicillin remained in E. faecalis, but there was an increase in resistance to penicillin and aminoglycosides.

Bone metastasis is one of the most common manifestations of advanced malignant process. Many tumors, especially breast, prostate and lung cancer, multiple myeloma, are characterized by a high incidence of bone damage (up to 7080 %) and clinical complications. Intense pain, hypercalcemia, spinal cord compression, pathological fractures, the need for radiation and surgical treatment (combined in the name «skeletal system related events») can occur even with single metastases. In the treatment of patients with bone metastases, a multidisciplinary approach is used; however, the basis is specific antitumor therapy and osteomodifying agents. They affect bone remodeling and microenvironment.

Objective: to evaluate the pharmacokinetics of nadroparin and dalteparin in thrombosis complicating the treatment of children with malignant neoplasms.

Materials and methods. The results of 52 pharmacokinetic studies performed in 34 patients with malignant neoplasms, whose treatment was complicated by venous thrombosis, were analyzed. The age of the patients is from 7 to 18 years, he median is 14.5 years. Depending on the value of daily dose and type of heparin administered, the results of pharmacokinetic studies were divided into 6 groups. Dalteparin sodium: during period of chemotherapy induced thrombocytopenia, subcutaneous injection at a dose of 51.0 (40.0-72.0) anti Xa IU/kg every 12 hours - 6 studies; subcutaneous injection every 12 hours at a dose of 100.5 (91.0-141.0) anti Xa IU/kg - 18 observations; long-term continuous administration at a constant rate at a daily dose of 201.0 (180.0-265.0) anti Xa IU/kg - 6 pharmacokinetic observations. Nadroparin calcium: 62.0 (53.0-71.0) anti Xa IU/kg every 12 hours - 6 studies; 93.5 (80.0-117.0) anti Xa IU/kg every 12 hours - 10 observations; subcutaneous injection at a dose of 203.0 (170.0-236.0) anti Xa IU/kg once a day - 6 pharmacokinetic observations.

Results. At steady-state, the area under the pharmacokinetic curve (AUC) of dalteparin and nadroparin, regardless of the mode of administration, depended on the maximum specific activity and half-life. No relationship was found for dalteparin between AUC and endogenous creatinine clearance. In contrast to dalteparin, the AUC after administration of na-droparin was closely related to endogenous creatinine clearance. The increase in chronometric indices indirectly reflected the presence of an anticoagulant in the blood, but did not allow an objective assessment of therapeutic effect achievement, recorded by the degree of thrombin generation inhibition.

Conclusion. There were no significant advantages of nadroparin compared with dalteparin when using in comparable doses in the case of venous thrombosis, complicated the treatment of children with malignant neoplasms. Subcutaneous administration of 50 % nadroparin calcium daily dose with 12 hours interval is preferred over a single administration of 100 % daily dose every 24 hours. It is mandatory to monitor the administration of low molecular weight heparins in children with oncological diseases in order to make a decision on the adequacy of anticoagulant dose to the therapeutic range.