Search

Relevance. The identification of determinants of the human genome, such as single nucleotide polymorphisms (SNPs), in association with various disease patterns, including infectious diseases, is one of the most actively developing areas of scientific research in the world.. Hepatitis C (HC), which remains a serious global health problem, belongs to the number of infections that attract the attention of specialists.Aims. Determination of genetic markers of hepatitis C virus (HCV) natural elimination and assessment of their role as a monitoring parameter of the epidemiological surveillance system.Materials and methods. The study included 660 people divided into 2 groups: persons with chronic HC (CHC) and blood donors (indicator group of the healthy population). In the studied groups, the following SNPs were typed: rs1143634, rs1143627 (IL-1B); rs4251961, rs419598 (IL1RN); rs1800795 (IL6); rs1800896 (IL-10); rs4986790 (TLR4); rs4374383 (MERTK). The associative relationship between SNPs and CHC alleles was identified using logistic regression analysis within four models (codominant, dominant, recessive, and overdominant). Additionally, the significance of polymorphisms at the intragenic and intergenic levels was assessed using modern bioinformatic resources in the field of functional genomics.Results. In this study, genotypes associated with the natural elimination of HCV were identified. Paired combinations of IL 1RA/IL-1B genotypes associated with the probability of the formation of CHC have been established. It is shown that synonymous SNPs can be associated with any characteristics of the pathological process, which can be explained by disequilibrium in coupling with functionally significant alleles of other genetic loci.Conclusion. The detection of the association of SNPs with clinical manifestations of the pathological process is not final and requires further study taking into account ONP coupling groups.

Protocol AML-MM-2000 treatment results of unfavorable prognostic group in children with primary acute myeloid leukemia (AML) in Russia and Belarus are presented. 105 children at the age from 2 weeks till 18 years (a median age — 10.8 years) are included in the study. In 91 patients (86.7%) hematological remission have reached, from them 34 patients (37.4%) are in the first continuous complete remission (CCR). 6-years overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) rate for all group of patients was 0.35 ±} 0.05; 0.32 ±} 0.04 and 0.43 ±} 0.05, respectively. Survival analysis of children with different cytogenetic anomalies has allowed to define two prognostic groups of patients: the intermediate prognosis, including patients with normal kariotype and t(9;11) which EFS and RFS rate was 40—50%, and unfavorable prognosis with EFS and RFS rate less than 40%. The efficiency analysis of three postremission therapy type (allogeneic and autological hematopoietic stem cells transplantation (HSCT) and chemotherapy (HT)) in intermediate and unfavorable prognostis groups was carried out. High efficiency of related HLA-identical HSCT in patients both intermediate and unfavorable prognostis groups have been shown. Autological HSCT is possible in intermediate prognosis patients with absence of HLA-identical siblings and in unfavorable prognosis patients with absence of HLA-identical unrelated donor.

Prognosis of patients with juvenile myelomonocytic leukemia not undergoing allogeneic hematopoietic cells transplantation (SCT) is dismal and not affected by any cytotoxic chemotherapy. Differentiating therapy is an attractive approach in JMML, due to ability of JMML cells to differentiate and die under influence of treatment with various agents in vitro. We report results of first-line treatment of 14 patients with JMML with 13-cis retinoic acid (RA) 100 mg/m2 daily peroral intake and low dose Ara-C - 25 mg/m2 daily for 10 days monthly. Complete remission (CR) or hematological improvement (HI) was obtained in 7 patients (50%). Four patients (median age at disease manifestation 5 months, median level of HbF —6,2%) achieved CR after a median of 9 cycles of therapy; in 3 patients the best response was HI (age at disease manifestation - 5; 7 and 46 months, HbF — 4,2; 8,0 and 51,7%) after 2; 3 and 5 cycles. Three out of 4 patients with CR are alive and have been in CR for 10; 17 and 30 months after start of therapy, acute lymphoblastic leukemia developed in one patient after 84 months of CR. Two patients with HI are still receiving treatment and have been in stable condition for 10 months after the initiating therapy, while 1 patient died after 8 months of therapy from catheter-related sepsis. The progression of the disease despite the treatment was registered in 7 patients (median age at disease manifestation 16,3 months, median HbF — 35,4%). We conclude that 13-cis RA in combination with low dose AraC may be useful in the treatment of patients younger than 1 year with low level of HbF, although the general paradigm of treatment of JMML with SCT remains unchanged.

Standard therapy of high risk patients with Langerhans cell histiocytosis (LCH) is associated with essential risk of therapy failure. In the present study results of 2-clorodeoxyadenosine usage as alternative therapy in this group of patients are analyzed. In this study 31 patients with multisystem form LCH with involving of organs at risk were included. Nineteen patients have received Prednisone and Vinblastine as front line therapy (standard group). Nine patients have received therapy with 2-CdA and cytosine-arabinoside (group 2-CdA). The patients in standard group statistically significant more often (55.5 % vs. 0 %, р = 0.0095) required second line therapy. Permanent disease conse-quences was more often developed in standard group (63.6 % vs. 0 %, р = 0.0147). The overall survival was 65.7 ± 12,8 % among standard group patients and 88.8% ±10% in 2-CdA group; p = 0.27. The event-free survival was in standard group 33.9 ± 12 %, in 2-CdA group – 88.8 ± 10 %, p = 0.0207. Severe hematological toxicity was observed at 2-CdA therapy. 2-CdA therapy is highly effective in treatment of high risk patients with LCH. The drug should be used only in a specialized hospital.

Healthcare facilities have always played an important role in transmission of bloodborne infections. Procedures involving blood and blood fluids pose a risk of transmitting hepatitis B, hepatitis C and HIV not only to healthcare workers, but also to patients. To assess the role of healthcare facilities in transmission of bloodborne infections and to identify risk groups among patients as well as transmission factors, a total of 75 outbreaks of hepatitis B, hepatitis C and HIV have been analyzed with reference to the data published in different countries in 2008–2020. The comparative analysis was conducted for the outbreaks in the United States during 1992–2008 and 2008–2019. Most of the outbreaks of bloodborne infections at healthcare facilities were caused by non-adherence to standard precautions among healthcare workers: Reusing disposable items; improper handwashing; reusing gloves; non-disinfecting surfaces, reusable equipment and devices; non-sterilizing reusable instruments. In terms of bloodborne infections, high-risk facilities include hemodialysis centers, oncohematology clinics, outpatient clinics, nursing homes, residential care facilities, and diabetes treatment centers. High-risk groups include patients undergoing hemodialysis, oncohematological patients, and patients with diabetes. Diagnosis of bloodborne infections on a regular basis, hepatitis B vaccination among high-risk patients, investigation of outbreaks, adoption of rules and procedures combined with training and compliance control of healthcare workers contribute to solution of the problem associated with nosocomial transmission of bloodborne infections.

Relevance. Hepatitis B is a global problem of global and Russian public health due to its high prevalence and the possibility of forming a chronic form of the disease with the development of cirrhosis and hepatocellular carcinoma. Aims. Assessment of the herd immunity to hepatitis B in the population of the Russian Federation in 2017‒2019.Materials and methods. The research was carried out at the Central Institute of Epidemiology within the framework of a large-scale program to assess herd immunity to hepatitis B in the population of the Russian Federation. The results of studies for the presence of anti-HBs in various subjects of the Russian Federation in 2017 to 2019, which were performed in accordance with MU 3.1.2943-11, were analyzed. Additionally, as a reference study in 2020, a survey of donors in Moscow (n = 427) was conducted for the presence of anti-HBs. Standard methods of descriptive statistics Microsoft Excel and STATISTICA 12.0 (StatSoft, USA) were used for statistical processing. The mean values were estimated taking into account the 95% confidence interval [95% CI] (according to the Klopper-Pearson method (exact method).Results. The average annual values of the proportion of persons with protective immunity against hepatitis B for 2017, 2018 and 2019 were 70.03%, 67.95% and 66.36%, respectively. Significant differences were revealed in the average values of the proportion of persons with a protective level of anti-HBs in the Federal Districts (FD): higher than the average Russian indicators were found in the Northwestern (74.2%), Southern (71.0%) and Far Eastern FD (70.7%). In 44 subjects of the Russian Federation during the observation period, the proportion of persons with protective immunity against hepatitis B was less than 60%.Conclusion. The necessity of optimizing the system of serological monitoring of post-vaccination immunity against hepatitis B is substantiated, which will increase the effectiveness of preventive measures nationwide

The incidence of leukemia in children in various regions of the Russian Federation ranges from 1.9 to 4.1 per 100 000 of children aged 0 to 14 years. If the average annual morbidity of children is below the Russian (3.03) or European (4.0) standard, it is possible that some cases of leukemia and other oncological and oncohematological diseases are not reported. Clinical-laboratory and instrumental manifestations of malignant diseases can be similar to other conditions. It should be borne in mind that the most frequent childhood diseases are infections. Fever combined with bone pain, unexplained hepato- and/or splenomegaly, lymphadenopathy, changes in the cellular composition of blood and increased LDH should be the reasons to exclude malignancy.

Candidemia is one of the most serious infectious complications in children with hematological malignancies and has a high morta lity rate.Seven-year experience of candidemia diagnosis and therapy in patients with various hematologic malignancies w as analyzed. Candidemia registered in 37 patients (AML and MDS — 14, ALL — 10, solid tumors — 5, histocytic syndromes — 4, AA — 3, other non-malignancy diseases— 2). C. non-albicans (36 isolates from 32 patients) was common cause of, while C. albicans isolated in 5 patients (8 strains). Antifungal prophylactic therapy was applied to 31 patients. 22 patients at the time of candidemia have neutropenia (< 0.5 × 10 9/l). Main clinical manifestations were febrile fever (100 % cases) and pneumonia (21.6 % cases). Less frequent multiorgan failure (8.1 %), septic shoc k (5.4 %), chronic disseminated candidiasis (5.4 %) and meningitis (2.7 %) were registered. All patients received antifungal therapy (monotherapy — 17, combination therapy — 20). Central venous catheter removed in 21 patients. In 14 patients hematopoietic recovery w as registered, none of these patients died, while from group of patients without hematopoietic recovery 6 patients died (p = 0.0001). Recurrent candidemia episodes were seen in 4 patients. Overall survival was 0.37 ± 0.09.

Aim. To analyze the results of allogeneic and autologous hemopoietic cell transplantations (allo- and auto-HCT) in children with acute myeloid leukemia (AML) from an intermediate risk group, most of which were performed using lower-intensity conditioning modes. Subjects and methods. The study enrolled 36 children from an intermediate risk group, who had undergone auto-HCT (n = 22) or allo-HCT (n = 14) in December 1994 to December 2008. The patients' age was 0.7 to 16.6 years (median 12.8 years). Chemotherapeutic conditioning regimens were applied to all the patients. Melphalan was a basic myeloablative agent in 83.3% of cases. Results. With a median follow-up of 4.6 years (1.1-13.8 years), three-year relapse-free survival (RFS) was 80.4%; overall survival (OS) was 65.6%. Recurrences were documented only in 6 (16.6%) patients from the auto-HCT. Transplantation-associated mortality (TAM) was 13.8% (five patients died). After allo-HCT versus auto-HCT, RFS, OS, and TAM were 100 and 68.7% (p = 0.03), 93.2 and 55.5% (p = 0.02), and 7.1 and 18.2%, respectively. Acute and chronic graft-versus-host reactions developed in 57.1 and 23.1%, respectively. Conclusion. Transplantation of allogeneic hemopoietic cells from a compatible related donor in the intermediate risk group children with AML, by using melphalan-based conditioning regimen, demonstrates a high survival rate with the minimum toxicity.

Aim. To analyze the efficiency of transplantation of the bone marrow from a HLA-compatible unrelated donor and continued immunosuppressive therapy (IST) in children with aplastic anemia (AA) unresponsive to 2 courses of IST. Subjects and methods. The study enrolled 14 children aged 2-16 years (median 9 years). A control group comprised 26 patients in whom IST was continued. The median interval between the diagnosis of AA and transplantation was 26 months (9-156 months). The conditioning regimen consisted of thoracoabdominal irradiation in a dose of 2 Gy, fludarabin (Flu) 100-150 mg/m2, cyclophosphamide (Cy) 100-200 mg/kg, antithymocyte globulin (ATG) in 11 patients and Flu, Cy, and ATG in 3. A graft-versus-host reaction was prevented with mycophenolate mefetil in all the patients, tacrolimus in 11, and cyclosporin A in 3. Donors were compatible for high-resolution typing of 10/10 and 9/10 alleles in 8 and 6 patients, respectively; the source of a transplant was bone marrow in 13 patients and granulocyte colony-stimulating factor-mobilized peripheral blood precursors in one case. Results. Thirteen patients achieved primary engraftment after single transplantation; one patient did after repeat transplantation. Grades I to II graft-versus-host reaction (GVHR) developed in 9 patients; postengraftment life-threatening infections in 3, extensive chronic GVHR in 2, circumscribed GVHR in 7. All fourteen hemopoietic cell transplant recipients followed for a median 17.5 months (range 1-71 months) were survivors. Conclusion. The likelihood of good survival after unrelated transplantations in AA is much higher than that after continued IST: 100% versus 15±11%.