Acute leukemias in children aged under 1 year has different clinical manifestations as compared to patients of older age groups. The prognostic values of ALL and AML in children under 1 year are different. In ALL there are additional independent risk factors which worsen the prognosis. Clinical researches in the field of infant acute leukemia is still under develop and making a significant contribution to the understanding of the biology of leukemogenesis and therapy. The results of therapy in different research groups were comprised: POG, CCG, COG (USA), JPLSG (Japan), Interfant (BFM, researchers from New Zealand, Australia and the USA). The difference of the results led to discrepancy regarding the role of allo-HSCT in the infants treatment. In Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, the 10-year OS after allo-HSCT in the pediatric group with high-risk infant leukemias was 55 %, in the group of patients with restructuring of the MLL gene – 53 % versus 59 % without MLL gene. The results of allo-HSCT depended on the disease stage at the time of treatment, in I–II CR 5-year OS was 79 % (n = 35), in III–IV CR or progression –16 % (n = 20).

Relevance. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only effective treatment method for the majority of patients with juvenile myelomonocytic leukemia (JMML). The authors of the article presented the experience of conducting HSCT in patients with JMML in the Russian Children’s Clinical Hospital.

Materials and methods. 55 HSCT for the period from 2003 to 2019 were performed in forty-two patients with JMML. 14 (33.3 %) patients from a related HLA-identical donor were given primary HSCT, 1 (2.4 %) from a related 9/10 HLA-compatible, 16 (38.1 %) – from unrelated HLA-identical, 6 (14.3 %) – from unrelated 9/10 HLA-compatible, 5 (11.9 %) – from haploidentical. The source of hematopoietic stem cells (HSC) in primary HSCT for 22 (52.4 %) patients was bone marrow (BM), for 13 (31.0 %) – peripheral blood stem cells (PBSC), for 4 (9.5 %) – cord blood (CB), for 3 (7.1 %) – BM in combination with CB. Twenty-two (52.4 %) patients received a myeloablative busulfan-containing conditioning regimen, 20 (47.6 %) – treosulfan-containing.

Results. The overall survival (OS) of patients for the entire observation period was 53 ± 8.3 %; transplantation lethality (TL) – 21.2 ± 6.8 %, relapse-free survival (RFS) – 72.0 ± 7.7 %, event-free survival (EFS) – 49.4 ± 7.8 %. The factors negatively influencing the results of HSCT in patients with JMML were the progression of the underlying disease at the time of HSCT, incomplete compatibility of the HSC donor, the use of CB as a source of HSC.

Conclusion. Indicators of OS, RFS, EFS patients with JMLL after HSCT are low. The reasons for treatment failure are TL, graft failure and relapse after transplantation. To improve the results of treatment of patients with JMML, careful selection of the donor and the source of HSC, the maximum possible reduction in the toxicity of conditioning regimens is necessary.

Relevance. In accordance with the guidelines on the clinical investigation of clotting factor VIII products of the European Medicines Agency and guidelines on pharmacovigilance of the Eurasian Economic Union, after registration of a new drug, it is recommended to study its efficacy and safety on a large population of patients in a standard medical practice to clarify and identify new data.

Materials and methods. In a prospective, multicenter, open-label, uncontrolled observational study, the efficacy and safety of the domestic recombinant B-domain deleted blood clotting factor FVIII (FVIII) (moroctocog alfa, Octofactor®, JSC “GENERIUM”) in patients with moderate and severe hemophilia A in the context of standard medical practice (study protocol number CI-51/15). Patients received the drug in terms of standard medical practice for the purpose of prophylactic treatment or on demand treatment. For prophylactic treatment Octofactor was administered to patients according to the instructions for medical use in a single dose of 20–40 IU/kg every 2–3 days. In the case of bleeding a single dose of Octofactor was calculated taking into account the severity and localization of bleeding in accordance with the instructions for medical use. The results of the treatment were analyzed for a period of 52 ± 2 weeks. The main parameter for evaluating the efficacy was the frequency of spontaneous bleeding that occurred within 48–72 hours after the administration of the Octofactor. Additional parameters for evaluating the efficacy included: the severity of spontaneous bleeding arising during the prophylactic treatment; the number of injections and the total dose of the Octofactor to stop 1 episode of bleeding; the amount of Octofactor used during the entire observation period (52 ± 2 weeks) and for 1 month both for prophylaxis and for stopping the bleeding that occurred; an indicator of the efficacy of therapy on the scale for determining the response to treatment of acute hemarthrosis (World Federation of Hemophilia, WFH).

Results. According to the results of the screening survey 237 male patients aged from 19 to 78 years old (mean age 35.2 ± 11.1 years) with moderate and severe hemophilia A (FAS-population) were included in the study. The efficacy of therapy was evaluated in 202 patients who underwent all the planned procedures during the observation period (PP-population). 193 (95.5 %) patients received prophylactic treatment, 9 (4.5 %) patients received on-demand treatment. Evaluation of the efficacy of treatment was carried out on the basis of basic and additional parameters. The main parameter for evaluating the efficacy – the frequency of spontaneous bleeding that occurred within 48–72 hours after the administration of the Octofactor – was 52 ± 2 weeks within 1.4 ± 2.9 cases. At the same time, the proportion of spontaneous bleeding that occurred within 48–72 hours after administration of the Octofactor preparation was 45.2 % of the total number of spontaneous bleeding and 15.6 % of the total number of all bleeding in patients who received prophylactic treatment. Among 608 spontaneous bleeding that occurred in patients receiving prophylactic treatment, 287 (47.2 %) of the bleeding were mild, 289 (47.5 %) were moderate and 32 (5.3 %) were heavy. Of the 275 spontaneous bleeding that occurred within 48–72 hours after administration of the study drug for prophylactic purposes, 117 (42.5 %) episodes were mild, 146 (53.1 %) were moderate, and 12 (4.4 %) were severe. With prophylactic administration the average single dose of the Octofactor was 2036.3 ± 884.7 IU, or 27.3 ± 11.2 IU/kg, in the treatment of bleeding occured during prophylactic treatment – 2227.7 ± 1087 IU, in the treatment of bleeding in patients receiving the drug only on demand – 2280.7 ± 1037.2 IU. The average monthly intake of the drug by one patient in prophylactic treatment was 19.75 ± 9.75 thousand IU, while the average monthly consumption of the drug for preventing bleeding from one patient was 17.16 ± 9.13 thousand IU for stopping bleeding against the background prevention – 3.87 ± 3.97 thousand IU. One patient who received on-demand treatment had an average monthly average of 13.47 ± 13.46 thousand IU of the Octofactor preparation. For stopping 1 bleeding, on average, 1.7 ± 1.7 injections of the Octofactor preparation were required, in the prophylactic treatment group – 1.8 ± 1.8, and in the on-demand treatment group – 1.5 ± 1.1. In the overwhelming majority of cases, patients of both groups showed excellent and good response to all treatment of acute hemarthrosis on the scale of the WFH on all visits, the reaction was moderate in a few episodes, and only in 1 case of acute hemarthrosis there was no response to the drug administration. The safety of therapy was evaluated in 228 patients who received at least 1 Octofactor administration during the study (mITT-population). There were 66 adverse events in 40 patients, 10 of them were associated with the use of the drug, the most significant of which were the formation of inhibiting antibodies to FVIII in low titer (1.5 U) in 1 patient and the development of allergic reactions in 2 patients.

Conclusions. Under the conditions of standard medical practice the efficacy and safety of Octofactor was confirmed for both prophylactic treatment and on-demand bleeding treatment in adult patients with severe and moderate hemophilia A.

The implementation of the state program “7 highcost nosologies” and the active work of Russian hematologists have significantly improved the specialized care for children and adults with Hemophilia. Russian hemophilia patient registry as of 10.25.2018 contained information about 7433 patients, of whom with hemophilia A – 6525 people. About 400 people were diagnosed with hemophilia with inhibitors. The inhibitor predominantly appeared at child and young age (up to 20 years). There is a high supply of coagulation factors concentrates for the treatment of hemophilia in the Russian Federation – 8.1 IU of coagulation factor VIII per capita in 2018, which corresponds to the graduation “full integration into society” according to the scale proposed by the World Hemophilia Federation. Due to the sufficient availability of coagulation factors, it is possible to conduct elimination of inhibitors by immune tolerance induction. Treatment with antiinhibitor coagulant complex and eptacog alfa (activated) requires a good venous access and is not always effective. Treatment results remain unsatisfactory in 67 % of adult patients with severe hemophilia with low inhibitor titer due to the number of bleeding per year exceeds 4. Unsatisfactory treatment results are noted in more than 1/ 3 patients with a high inhibitor titer, despite the ongoing prophylaxis with bypassing agents. Currently, clinical studies of fundamentally new drugs for hemophilia treatment, including the inhibitory form, are ongoing. One such drug is emicizumab, which is a bispecific humanized monoclonal antibody that bridges activated factor IX and factor X to restore the function of missing activated factor VIII Emicizumab is not neutralized by inhibitors to FVIII, which allows it to be successfully used in the inhibitory form of hemophilia A. The results of HAVEN 1 and HAVEN 2 studies showed the advantages of using emicizumab in prophylactic regimen in children and adults with the inhibitory form of hemophilia A compared with bypassing agents.

Neuroblastoma (NB) is the most common extracranial embryonic tumor in children with a variety of molecular biological and clinical characteristics. There is no single molecular genetic mechanism involved in the pathogenesis of NB, which determines its heterogeneity. Pathogenetically important event in the development of NB are aberrations of ALK gene (Anaplastic lymphoma kinase), which are found in 70 % of patients with familial form of NB and in 7– 10 % of patients with sporadic cases. ALK oncogene encodes a receptor of the same name, expressed on the membrane of cells of the central and peripheral nervous system, which is in the activated state in NB. The negative effect of ALK gene anomalies on the prognosis in patients with different risk groups of NB is described. ALK gene aberrations are more often detected duringrelapse and refractory course of the disease. Because of its tissue specificity, ALK protein is an ideal target for targeted therapy. This article presents a literature review of the role of ALK in NB.

The possibilities of traditional methods of diagnosis (radiological and morphological) of brain tumors are now almost exhausted. With their availability and visibility, they have a number of drawbacks in the form of risks of subjectivity in the evaluation of images and microscopic pictures, limited capabilities of existing equipment, the need to use invasive techniques to obtain material. In addition, they do not meet the requirements for individualization of treatment methods, which becomes available as knowledge about the molecular genetic characteristics of tumors deepens. Developed in recent years, the method of “liquid biopsy”, based on the definition in the biological fluids of cells or other components of the tumor has shown its informative in a number of malignant tumors of internal organs. With its help, it is possible to identify the genotype of the tumor and on this basis to individualize the treatment process, as well as to evaluate its effectiveness. The process of finding methods and developing techniques for noninvasive diagnosis of refined genotypes of brain tumors is currently under development. By identifying tumorspecific markers in peripheral blood and cerebrospinal fluid, it is already possible to identify the presence and condition of IDH1 and MGMT genes that are critical for gliomas and to start solving the problem of individualization of therapy.

Teratomas are germ cell tumors consisting of derivatives of 3 germ layers and havingvarious malignant potential – from benign mature forms to immature embryonic and forms with somatic type of malignancy.

This article describes the clinical caseof rare localization of mature teratoma – retroperitoneal space, aswell asan example of multidisciplinary interaction of clinicians, radiation diagnosticians and pathomorphologists in correct preoperative diagnosis using computed tomography, successful surgical treatment and histological verification of extraorgan teratoma of the retroperitoneal space.

Chronic myeloid leukemia (CML) in children is rare, less than 3 % of all cases of leukemia in pediatric practice. Along with the successes achieved in the treatment of CML with imatinib, it’s necessary to study of molecular factors in predicting resistance to therapy. According to the literature, about 30 % of adult patients with imatinib resistance have point mutations in the kinase domain of BCR-ABL1 gene. The number of reports about mutation spectrum of the BCR-ABL1 gene in children with resistant forms of CML is limited. This article describes the clinical case of secondary resistance to imatinib in a 15-year-old girl with the F359C mutation of BCR-ABL1 gene and a review of the literature.

The article presents a unique clinical observation of adrenocortical cancer (ACC) in a newborn baby, whose mother suffered from a recurrent form of maxillary fibrosarcoma and had a burdened obstetric and gynecological history, but was not examined by a geneticist. Complications of ACC in the presented patient were secondary hypertrophic cardiomyopathy with obstruction of the exit paths of both ventricles, Itsenko– Cushing syndrome. Despite the surgical treatment carried out according to vital indications (tumoradinectomy on the right with hormonal support with a Solu-Cortef), the child died during the progression of multiple organ failure and sepsis.

This article is devoted to the analysis of problems associated with the state of the endocrine system in patients who have undergone a malignant neoplasm in childhood. The main diseases and pathological conditions that can develop in this population are considered. The risks of the development of pathological changes on the part of the endocrine system, treatment and prevention are described. Separately analyzed the issue of hypopituitarism, adrenal insufficiency, hyperprolactinemia, growth hormone deficiency, impaired thyroid function, early puberty.

In the city of Sochi, in 1986, one of the first children’s hematology department in the USSR was opened. The characteristic features of the profile service of the Krasnodar Region are a strong school of professional doctors based on russian and foreign experience, the continuity of generations, close cooperation with leading federal centers and many years of fruitful work.

Today, the Department of Oncology and Hematology with chemotherapy for 70 beds in the 24- hour in- patient department and 30 beds in the intensive care ward operates in Krasnodar. In addition, the hospital has a 30- bed oncology department for patients with solid tumors and tumors of the central nervous system. The expansion of the service is planned for 2023: a day hospital for oncohematological patients, a bone marrow transplant unit and a blood transfusion department with a cryopreservation station for hematopoietic stem cells.

Krasnodar Region has been keeping a child cancer registry for more than 40 years. The article presents the main stages of the development of hematological and oncological assistance to children of the Krasnodar Region, the activities of the service now and its plans for the future.