Introduction. Neuroblastoma (NB) is the most common extracranial solid tumor in infants, but it is more rarely found in older children. Only 1–2 % of cases are registered in adolescents and young adults. The long-term prognosis in these patients is highly unfavorable due to indolent clinical course formed by peculiar biological characteristics of tumors. We publish a case study of 11 patients with NB older than 10 years at the time of diagnosis.

Case series description. In 2008 to 2020 a total of 11 adolescent and young adults patients with median age of 14 (10–28) years were treated in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg. Seven of 11 patients had mediastinal neuroblastoma, in other cases the primary lesion was abdominal (n = 2), pelvic (n = 1), and in one case no primary lesion was defined. Ten of 11 patients had primary disseminated disease with lymph nodes (n = 5), bone (n = 5), bone marrow (n = 3), or hepatic (n = 1) metastases. Tumor morphology and cytogenetics were assessed in all patients, in 4 cases additional targeted sequencing of potentially pathogenic genes was performed. All patients received chemotherapy and local control measures according to high-risk NB guidelines, in 7 of 11 cases additional chemotherapy regimens were used. Seven of 11 patients also received dose-intensive consolidation with autologous hemopoietic stem cell transplantation (auto-HSCT). In case of primary resistance MIBG-therapy, targeted or immunotherapy were used. In 6 cases tumor morphology corresponded to undifferentiated neuroblastoma, in 5 cases to ganglioneuroblastoma. Although all cases were high-risk, they mostly lacked high-risk biological features seen in younger patients. None had MYCN amplification, the cytogenetic assay yielded the following aberrations: +2 (n = 2), del1p (n = 1), g17q (n = 1). All patients, in whom the targeted sequencing was performed had pathogenic mutations: ATRX (in two patients 19 and 28 years at diagnosis), TP53 and PIK3CA, FBXW7. Nine of 11 patients had primary resistant disease, in 7 cases response was obtained on second or subsequent therapy lines. Two patients responded two chemoand targeted therapy combination, in 3 cases monoor combined immunotherapy yielded prolonged (16–32 months) response. Six of 7 auto-HSCT recipients developed a relapse. 6 out of 11 patients are currently alive. In 2 cases, a complete response is maintained according to scintigraphy with ¹²³I-MIBG, lasting 86 and 14 months after completion of therapy.

Conclusions. NB is biologically different in adolescents and young adults. It is characterized by indolent clinical course with very high risk of late relapse. As most patients in this group are chemoresistant, the standard dose-intensive tactics may be less effective and perhaps more attention should be given to targeted and immunotherapy-based approaches.

Vascular anomalies (VA) comprise a heterogeneous group of diseases associated with congenital angiogenesis disorder. There are no currently developed unified protocols and treatment regimens for systemic forms of VA. Numerous advantages show sirolimus, an mTOR inhibitor, as a well tolerated and effective antiproliferative and antiangiogenic therapy in patients with VA. The article presents the results of treatment of 211 patients with VA (6 patients with vascular tumors and 205 patients with vascular malformations) aged 2 months to 17 years (median – 9 years), who received sirolimus therapy for 1–86 months (median – 24 months). Sirolimus was administered at a starting dose of 0.8 mg/m²/day orally in two doses with an interval of 12 hours. The concentration of the blood preparation was maintained in the therapeutic range of 6–15 ng/ml. Since 2015, concomitant therapy with co-trimoxazole for the prevention of Pneumocystis pneumonia has been prescribed only to tracheostomy carriers. When infectious episodes occurred in patients, sirolimus therapy continued without changes in the dose of the drug and did not affect the disease, provided that the therapeutic concentration was maintained. A positive response to therapy was observed in 89.1 % of patients with VA in the form of the size of the vascular mass according to the data of visual examination and instrumental control. All patients showeda clinical response to therapy in the form of relief of painsyndrome, reduction/relief of lymphorrhea, reduction/improvement of hemostasis parameters, and an increase in functional activity and quality. For the entire observation period 2012–2020, when taking sirolimus, not a single severe adverse event occurring in post-transplant patients has been reported that would require discontinuation of the drug. The article presents two clinical cases of sirolimus use in the treatment of patients with kaposiform hemangioendothelioma and extensive venous malformation. Parents are encouraged to use the information in scientific research and publications.

Relevance. The experience of loss by a child receiving antitumor treatment is a factor in the development of psychopathologies.

Purpose to study is to study the specifics of family losses in pediatric oncology; to trace the dynamics of grief during analytical psychotherapy in children who have lost one or both parents.

Materials and methods. The study of the specifics of family losses was carried out by the method of retrospective analysis of the dynamics of family relations in 1298 families. To study the dynamics of grief in the process of psychotherapy, 13 children aged 3 to 13 years who lost one or both parents were selected.

Results. Antitumor treatment of the child is accompanied by prolonged separation from one, less often both parents, and, in 13.3 %, the loss of a mother or father as a result of a divorce/death. Burning in all the examined children was complicated with the appearance of a number of somatic, emotional-behavioral, mental symptoms that worsen their physical condition and psycho-emotional status. As a result of psychotherapy, the child can react to suppressed negative emotions, which leads to the disappearance of symptoms of grief.

Conclusion. The interaction of pediatricians, clinical psychologists, social work specialists is productive in order to provide timely psychotherapeutic assistance to the child before the manifestation of symptoms of complicated grief manifestation.

Relevance. Ewingʼs sarcoma (ES) is a classic representative of the extensive family of ES tumors, which occupies one of the leading positions among the malignant pathology of the musculoskeletal system in children and adolescents. This group is characterized by an extremely large variety of morphological, immunohistochemical, and molecular genetic characters among its representatives. The absence of specific pathognomonic markers for ES, as well as the presence of wide variability of clinical manifestations complicates the differential diagnosis. 

Materials and methods. The study included patients of childhood and adolescence with a localized and generalized form of ES/PNEТ of various localizations undergoing treatment in the conditions of the Department of Pediatric Oncology of the Federal State Budgetary Research Center for Oncology from 2009 to 2019. As the material, the tissue of the primary tumor of ES/PNEТ from paraffin blocks was used, obtained from 67 patients during the primary biopsy, as well as after the surgical stage as part of a combined or complex treatment. The expression of ZEB1 was determined immunohistochemically.

Results. The highest average level of expression of ZEB1 protein was observed in group 4 with a generalized form of ES (surgical material) and amounted to 60.8 ± 2.2 %, the minimum level was detected in group 2 with a localized form of ES (surgical material) and amounted to 29.2 ± 3.0 %. Between groups 2 (localized form) and 4 (generalized form) statistically significant differences were noted (p = 0.026).

Conclusion. As a result of an immunohistochemical study, the ZEB1 protein showed its prognostic significance when comparing groups with a localized and generalized form of ES (p = 0.026). The predominance of the expression level of ZEB1 protein in the group with the generalized form statistically significantly increased the chances of metastasis by 3.6 times (95 % CI 1.13-11.8).

The COVID-19 pandemic has exposed pain points of decentralized healthcare systems in the global world and a failure in scientific systems analysis of old and new infections. Eighteen years ago severe acute respiratory syndrome (SARS) was underestimated and etiopathogenetic research conducted around the world was not used to develop effective treatments and prevention of the disease. Moreover, the anti-epidemic tactics in the recommendations of the World Health Organization and national health systems in the fight against the pandemic were inconsistent and relied on the historical experience of the influenza pandemic and other epidemics of respiratory infections with an emphasis on the study of the biology of the pathogen and the adaptation of society to establish biological and social balance with it.

The study of the SARS-CoV-2 virus (severe acute respiratory syndrome-related coronavirus 2) from the point of view of its origin, genome, mutated strains, damaging factors in cell culture in vitro and autopsies in experimental animals and humans in foci of infection in no way answers the question of the reasons for the various responses of the host, including asymptomatic carriage with/without the formation of an immune response; definition of syndromic complexes and their periodization; options for the uncomplicated and complicated course of the disease; outcomes, including recovery with/without the formation of specific immunity and thanatogenesis, with the search for evidence of direct or indirect involvement of SARS-CoV-2 virus in adverse outcomes.

The underestimation of the host's responses to the effects of beta-coronavirus has led to syndromic polypharmacy using more than 30 drugs with anti-inflammatory, antiviral, antibacterial, anticoagulant, immunosuppressive, and other effects, including passive immunotherapy with plasma of recovered patients or therapeutic exchange plasmapheresis. Seven months of the fight against COVID-19 led, as one would expect, to the proven effect of only tough anti-epidemic measures, personal protective measures and hygiene in the absence of effective treatment and prevention measures. In fact, an empirical selection of national and international treatment protocols with a combination of non-specific syndromic drugs is underway in the world.

The critical review discusses scientific data and hypotheses of the origin of a new coronavirus infection, human ontogenetic response to infection with SARS-CoV-2, and emerging bioinformatic concepts of the pathogenesis of the disease and approaches to pathogenetic treatment.

Rare bleeding disorders include inherited deficiencies of fibrinogen, factors (F) II, FV, FVII, FX, FXI, FXII, and FV + FVIII, as well as a multiple deficiency of vitamin K-dependent coagulation factors. Some of these deficiencies are more studied, due to the large number of patients, some are extremely rare, so at this stage it is quite difficult for them to develop a universal approach to therapy and prophylactic treatment. The purpose of this review was to evaluate the frequency, clinical manifestations, genetic basis, possibilities and difficulties of diagnosis for these deficiencies.

Malignant neoplasms occupy one of the leading places in the structure of infant mortality. This article provides an overview of current information on the epidemiological features and systems of cancer accounting in children in Russia and the world. The described methodologies for reporting cases of childhood cancer in developed countries can serve as a guideline for improving the domestic pediatric oncology service.

Packed red blood cells are important part of modern treatment recommendations of anemic syndrome in benign and malignant diseases of hematopoietic system in both adults and children. Special features of iron metabolism in the human body after erythrocytes-containing transfusions lead to its increased accumulation in organs and tissues and post-transfusion iron overload development. Clinical manifestation of post-transfusion iron overload varies, but in the absence of chelation therapy can lead to life-threatening complications. This literature review describes the main causes of iron overload, clinical features, and diagnosis and treatment of iron overload.

The recent chemotherapeutic approaches to acute myeloid leukemia (AML) management reached the limits, achieving overall survival rate of approximately 70 %. An intensification of chemotherapeutic regimens is barely possible due to high level of toxicity and risk of lifethreatening complications. The modernization of program therapy of AML involves the clinical application of achievements in molecular biology, immunology and cytogenetic of the tumor cell. The researches in fundamental oncology revealed the phases of leukemogenesis and defined selective ways of targeted therapy in the treatment of AML.

Associated hematopoietic stem cell transplantation (HSCT) or transplant-associated thrombotic microangiopathy (TA-TMA) is currently a generally recognized and severe complication of HSCT with a high risk of mortality. TMA is characterized by microangiopathic hemolytic anemia and thrombocytopenia, resulting in the accumulation of platelets in the microvasculature, which leads to dysfunction of the ischemic organ. The pathogenesis of TА-TMA is based on endothelial damage by various trigger factors (in particular, chemotherapeutic agents in the conditioning regimen, the use of calcineurin inhibitors, alloreactivity, infectious agents). The article presents the peculiarities of terminology, pathogenesis and clinical manifestations of TA-TMA, methods of therapy for this pathology. Examples of management of patients with TA-TMA are demonstrated using a clinical example.

Veno-occlusive liver disease (VOD), now more often referred to as “sinusoidal obstruction syndrome” (SOS), is a symptom complex that develops in the early stages after hematopoietic stem cell transplantation and some chemotherapy regimens due to the toxicity of a number of drugs used and accompanied by the following symptoms: hyperbilirubinemia, fluid retention, weight gain, and painful hepatomegaly. According to various sources, the incidence of SOS/VOD in patients with oncohematological profile ranges from 3 to 15 %. At present, the standard schemes for the prevention of this condition are not fully recommended. The article presents a brief review of the literature, representing international experience in the study and treatment of SOS/VOD.

Pneumoniasinpatientswithhempblastoses, arisingduringtreatmentinsettingofmyelotoxicagranulocytosis, arelife-threateningcomplications, which press complex approach for diagnosis and treatment. In condition of new coronavirus infection COVID-19 pandemia, differential diagnosis of pneumonia with “ground glass” lung changes is a hot issue. In the current paper we present world data on clinical, laboratory and X-ray diagnosis of SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) pneumonia in children. Special attention is paid to X-ray features depending of child age. It is provided two clinical examples, demonstrating a necessity of complex microbiological, immunological, molecular and X-ray diagnosis for detection of lung change genesis in oncohematologic patients.

Thymic carcinoma (TC) belongs to a group of rare thymic epithelial tumours (TETs) arising from the anterior mediastinum. One of the most relevant established prognostic factors is complete surgical resection. Given the high invasive potential of TC a lot of patents at the diagnosis present with a locally advanced or metastatic disease, therefore complete resection could not be achieved, and a role of systemic therapy is increasing. Due to the rarity of this tumor type in children and adolescents, treatment approaches based on the guidelines for management of TETs in adults. In this article we report a case of TC in a 2-year-old boy. The literature review describes the current histological classification of the TET, approaches for systemic chemotherapy and local control in patients with TC.

Nephrogenic rests and nephroblastomatosis describe persistence of embryonic renal parenchyma (metanephric blastema) beyond 36 weeks of gestation, when nephrogenesis is normally complete. This persistent metanephric blastema may transform into the Wilms tumor, and are detected in 30–40 % of unilateral nephroblstoma and nearly 100 % in bilateral cases. The risk of Wilms tumour is increased in any type of nephrogenic rests/nephroblastomatosis but it is higher in infants and in patients with intralobar nephrogenic rests. We cite below several studies described different types of nephrogenic rests, their connection with nephroblastoma development and the details of diagnostic. We refer to clinical examples, in that regard. Two cases are presented: bilateral diffuse hyperplastic perilobar nephroblastomatosis in one child and an infant with combination of perilobar nephrogenic rests in one kidney and Wilms tumour in the other kidney.

The most common extracranial solid malignant tumor of childhood – neuroblastoma (NB) is characterized by the presence of two metastatic forms (stages 4 and 4S). Stage 4S is described to have metastatic spread to the liver, skin, and minimal bone marrow invasion. Certain rare localisations of NB metastases (pleura, testicles, and others) may not worsen the prognosis in children of the first year of life in the absence of severe bone marrow invasion and metastases to the skeletal bones. The article describes a clinical case of retroperitoneal NB with atypical metastasis to the pleura in a child of the first months of life with a favorable outcome with a minimum amount of chemotherapy.

Recently, in the intensive care of acquired coagulopathies in children and newborns, synthetic coagulation factors have occupied an important place, with recombinant VII activated coagulation factor (rFVIIa) being used more often. It initiates hemostasis at the site of vascular damage, forms a complex with tissue factor, and ensures maximum platelet activation. The resulting complex stimulates the transition of blood coagulation factors IX and X to the active form IXa and Xa, then factor Xa leads to increased synthesis thrombin and the formation of a stable fibrin clot. Initially, rFVIIa was developed and used to treat bleeding and surgery in patients with hereditary or acquired hemophilia and a high titer of an inhibitor to coagulation factors VIII or IX. Currently, indications for its use have expanded significantly and it is effective in intensive therapy of other acquired coagulopathy, including the occurrence of coagulopathy due to sepsis. This article presents a clinical case of the successful use of rFVIIa in a newborn with sepsis and hemocogulation disorders. The description of each case is important for the accumulation of experience and the development of further algorithms for the treatment of newborns with sepsis, accompanied by impaired hemocoagulation, since there is currently no single effective management strategy for such patients.

Background. In 2018, Eurasian Alliance in Pediatric Oncology (EurADO) members identified pediatric hematology/oncology nursing education as a regional priority. In most participating Eurasian countries, pediatric hematology/oncology nursing is not recognized as a subspecialty; thus, subspecialized education offerings may be limited. A working group of nurse leaders was formed to set nursing priorities to advance pediatric cancer nursing and subspecialized education in the region. As an initial project, members determined a need to develop a train-the-trainer course for regional implementation to improve nurses’ subspecialty knowledge.

Purpose/Objective. A needs assessment was conducted to evaluate Eurasian nurses’ pediatric hematology/oncology education needs to inform the development of a pediatric hematology/oncology nursing train-the-trainer course in Eurasia.

Design/Methods. From August to September 2019, a paper-based needs assessment was disseminated in English and Russian to working group members for dissemination to pediatric cancer nurses in their hospitals. Items included multiple choice, yes/no, Likert-type scale and open-ended questions. Questions assessed participant demographics, subspecialty education topics of interest and perceived high-risk issues for nurses and patients.

Results. Responses were received from 233 nurses representing 13 hospitals in 9 countries. Priority topics of interest included overview of pediatric cancers and treatment, chemotherapy administration and side effects, oncologic emergencies and vascular access. Nurses reported that patients in their settings were at high-risk for infection, depression/psychological issues, treatment-related side effects and complications. Perceived high-risk areas for nurses included stress/burnout, high workloads/short-staffing, hazardous drug and blood borne pathogen exposure and limited equipment.

Conclusion. Survey findings reveal a lack of subspecialty pediatric hematology/oncology education opportunities for nurses practicing in Eurasian hospitals. The Eurasia Pediatric Hematology/Oncology Nursing Course was developed based on survey results and is currently being implemented across centers in the region.

This work is devoted to the analysis of problems associated with the organs of hearing and vision in patients who survived a malignant neoplasm in childhood. The main diseases and pathological conditions that can develop in this population are considered. Risks of the development of pathological changes in the organs of vision and hearing, treatment and prevention are described. The issues of cataracts, strabismus, atrophy of the lacrimal ducts, hearing loss and many others are analyzed separately.