Introduction. Mastocytosis occurs due to clonal mast cells proliferation and may have different clinical course. As the disease only rarely occurs in pediatric population there are very few clinical observations describing its symptoms, prognosis and therapy response in pediatric cohorts.

Aim of the study — characterization of gender, sympthoms, prognosis and therapy in children with mastocytosis using data obtained by electronic parent survey.

Methods. The study data was collected from November 2014 till August 2020 from parents referring for consultation of hematologist via “Vkontakte” social network. All parents completed two surveys. The first one was performed right after the referral, the second one was performed from May 2020 to August 2020. The data on age at symptoms onset, family history, symptoms, rash distribution, serum tryptase concentrations, sunlight sensitivity and clinical course was obtained and analyzed.

Results. The data on 163 children was obtained, 86 (52.7 %) of them were boys and 77(47.3 %) were girls. The median age was 6 (0.5—22) years. At the end of survey the median observation time was 61.5 (2—276) months. The most common mastocytosis clinical variant was urticaria pigmentosa (n = 129; 79.1 %), mastocytoma in 18 (11 %) and in 15 (9.9 %) an unknown variant was observed. The diagnosis was based on skin biopsy in 19 patients (11.6 %). Characteristic symptoms were seen in 123 (75.4 %) children. The main complaints were skin reaction triggered by various factors (n = 89; 72.3 %) and itching (n = 78; 63.4 %). Most patients took antihistamines (n = 64; 61 %) and ketotifen (n = 22; 21 %). The second survey was conducted in 139 (85.2 %) pts. At the time of survey symptoms progression was seen in 4 (2.9 %) patients, while in 42 (30.2 %) cases stabilization, and in 93 (66.9 %) cases improvement were observed.

Conclusion. The symptoms onset mostly occurs in the first year of life. Most frequents symptoms are itching and rash in response to various triggers. Antihistamine drugs led to symptoms mitigation. The clinical course is benign in most children.

Relevance. One of the leading positions among malignant tumors of the musculoskeletal system in children and adolescents has recently begun to be occupied by Ewing’s sarcoma (ES). The prognosis of patients suffering from this onconosology remains extremely unfavorable even in the absence of distant metastases and timely initiation of antitumor treatment. The authors present 10 years of experience in the management of pediatric and adolescent patients with ES in the pediatric oncology department of the National Medical Research Center of Oncology, Ministry of Health of Russia.

Materials and methods. The study included pediatric and adolescent patients diagnosed with ES of I—IV stages of various localizations, who were treated in the Pediatric Oncology Department of the National Medical Research Center of Oncology, Ministry of Health of Russia in the period from 2009 to 2019. We analyzed 2- and 5-year overall (OS) and event-free (EFS) survival in patients who received combined and complex antitumor treatment for various forms of tumor dissemination according to the EURO-EWING 2008protocol, which included neo-and adjuvant polychemotherapy, including high-dose, radical surgical treatment, and also radiation therapy.

Results. The median 5-year OS and EFS in the general group of the studied formulations was 60 and 17 months, respectively. The indicators of 2- and 5-year OS and EFS in patients of the general group were 80.6 % and 56.7 %, 38.6 % and 10.6 %, respectively. The volume of the performed antitumor treatment, as well as the form of the advanced tumor process, did not have a significant effect on OS and EFS indicators (p > 0.05). At the same time, the chances of developing ES in boys were statistically significantly higher by 2.2 times in comparison with girls (95 % confidence interval 1.1—4.3).

Conclusion. The obtained OS and EFS indices indicate unsatisfactory results of anticancer therapy and extremely high aggressiveness of the biological behavior of the tumor, regardless of the form of spread of the tumor process.

Introduction. Distinguishing between Von Willebrand disease (vWD) types often requires multimer gel analysis. The current techniques for vWF multimer structure are manual, complicated, non-standardized and time consuming. The aim of this study was to evaluate diagnostic capabilities of new automated vWF multimer screening assay.

Materials and methods. Children with vWD, acquired von Willebrand Syndrome (aVWS) and 8 healthy donors as a control group were enrolled in this study. Von Willebrand factor antigen (vWF Ag); ristocetin cofactor activity (VWF:Rco); vWF collagen binding (VWF:CB); ristocetin-induced platelet aggregation (RIPA); factor VIII clotting activity (FVIII:C) and vWF factor VIII binding activity (vWF:FVIIIb) were performed to evaluate vWD. Multimer analysis was carried out using the commercial HYDRAGEL 5 von Willebrand Multimers kit on semi-automatic gel electrophoresis instrument HYDRASYS (SEBIA).

Results. The samples from control group had 9—12 bands of vWF multimers with the same distribution as control plasma. Patients with type I vWD had the proportional decrease in the intensity of the bands with preservation of the normal distribution of the band. Patients with type III vWD reveal the complete absence of the multimer bands on the gel. Multimer analysis in type IIA shows the absence of high molecular weight multimer bands. In other patients the distribution of vWF multimers was normal against the changes in functional properties of vWF (types IIM, N). Most of the children with aVWS also revealed normal distribution of vWF multimers, however, in some patients, the slight decrease in large multimeric forms was observed visually on the gel.

Conclusion. Multimer analysis allows to visualize the multimer distribution in various types of von Willebrand disease. The method is easy to perform and can be useful for distinguishing between the subtypes of vWD. But only the full test panel including genetic tests would allow the differentiantion of vWD types with high precision.

Introduction. Adrenal cortical carcinoma (ACC) is a rare cancer but is the most common primary cancer in the adrenal gland. Despite the low incidence of ACC the mortality rate ranges from 0.04 to 0.2 %, in the overall structure of cancer mortality. Treatment of ACC is mainly surgical and radical surgical excision is the treatment of choice for local disease stages.

Aim of the study — to present our results of surgical treatment of localized and locally advanced ACC in children and to determine the risk factors of relapse.

Materials and methods. Twenty-eight patients (median age of 47.8 (06—216) mo.) with localized and locally advanced ACC underwent a retrospectively analysis. Stage I, II, and III revealed in 12 (45 %), 7 (25 %), and 9 (30 %), respectively. In 19 (68 %) cases the secretion of one or more hormone observed. Macroscopically and microscopically complete resection were performed in 26 (93 %) and 23 (82 %) patients, respectively. The median tumor volume was 183 (3.6—1608) cm³ and the median tumor weight was 207.9 (48—710) g.

Results. Five-year overall (OS) and relapse-free (RFS) survival were 71 % and 69 %, respectively. OS and RFS according to stage I, II, and III were 100 % vs. 71 % vs. 17 % and 100 % vs. 71 % vs. 14 % respectively. The radical surgical resection and the level of Ki-67 expression influenced significantly the rates of OS and RFS (p < 0.001).

Conclusion. The main factor affecting the survival rate of ACC in children with stages I—III is the radical surgical resection. It should be taken into account when planning postoperative therapy. Some of biological characteristics of the tumor could also significantly affect the results of treatment.

Introduction. Standard eye enucleation (EE) may not always guarantee a sufficient length of resection of the optic nerve (ON) so that the tumor cells do not spread along the optic nerve at the intersection line. Surgical access and the scope of surgical intervention are determined by the spread and localization of the tumor, as well as the qualification of the operating team.

Purpose — to evaluate the role of extended surgical interventions in the spread of extraocular tumors on the ON.

Materials and methods. The study included 9 patients with retinoblastoma (RB) and macroinvasion of the ON during primary magnetic resonance imaging (MRI) and/or micromorphological invasion of the ON resection line after EE. 4 of the 9 patients were treated with primary/secondary EE, induction chemotherapy (CT) and high-dose CT (HDCT), radiation therapy (RT). 5 out of 9 patients underwent secondary extended surgical interventions: exenteration of the orbit (n = 1), osteoplastic lateral orbitotomy with precanal resection of the ON (n = 2) in combination with EE in one case, subfrontal craniotomy (n = 1) and orbitozygomatic craniotomy (n = 1) with prechiasmal resection of the ON and EE with adjuvant RT (excluding the latter case) and CT, without HDCT.

Results. It should be noted that the overall survival (OS) of 5 patients with complete microscopic resection (R0) after extended secondary operations was 75 ± 0.217 % with an average follow-up period of 77.25 ± 18.8 months, while in 4 patients with R1 (n = 4) without secondary extended operations with HDCT reached only 50 ± 0.25 % with an average follow-up period of 57 ± 24.8 months.

Conclusion. MRI is mandatory for the primary diagnosis of RB, especially when there is a risk of the tumor spreading through the ON. Secondary surgery with R0-resection has a positive effect on survival. The need for adjuvant RT and CT after surgery should be discussed.

Introduction. So far there has been no clear protocol on the treatment of bacterial infections in hematopoietic cancer patients undergoing polychemotherapy (PCT) and hematopoietic stem cell transplantation (HSCT). Guidelines available from antibiotic therapy panels such as EMBT, NCCN, ECIL, Sepsis-3 often fail to cover the entire spectrum of clinical risk factors of severe complications caused specifically by multiresistant Klebsiella pneumoniae.

The aim of the study — is to showcase the clinical experience of demonstration of the experience of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin Russian Cancer Research Center with respect to adjusting antibacterial therapy for the spectrum of microorganisms found in the patient before the onset of antitumor therapy, and for the multiresistant microorganism findings in patients with blood cancers and febrile neutropenia (FN) undergoing PCT and HSCT.

Materials and methods. The study involved five patients undergoing either PCT or HSCT for hematopoietic cancers at Research Institute of Pediatric Oncology and Hematology in October 2019 — October 2020, multiresistant Klebsiella pneumonia colonies found in each case. Results. Five patients with hematopoietic cancers and induced bone marrow aplasia were found to have multiresistant Klebsiella pneumoniae colonies on top of post-PCT/HSCT immunosuppression. Given high risk of death, these patients need early antibacterial therapy with reserve antibiotics outside standard empirical antibacterial treatment protocols should they develop FN. The Center's practices have shown that baseline protocols are often inadequate to the severity of these patients' conditions in a certain timeframe.

Conclusions. To sum up the Center's limited experience, the finding is that additional research is required into the factors of risk of severe multiresistant Klebsiella pneumoniae infections in patients undergoing PCT and HSCT; algorithms must be developed for the treatment of patients in such a critical condition.

Immune checkpoint inhibitors (ICT) therapy is a successful immunotherapy (IT) strategy that is quite effective in a number of patients with non-small cell lung cancer, melanoma, bladder cancer, breast cancer and others. Nevertheless, there is a need in predictive markers for ICT therapy for personalized IT as far as there is a large group of patients, the proportion of which varies depending on the tumor, who do not have a clinical response to such therapy. The review summarizes the theoretical aspects and results of clinical trials dedicated to various clinical efficiency predictor using modern databases. As a result of the analysis it is established that the main candidates for the role of such markers are tumor infiltrating lymphocytes and their subpopulations, peripheral blood lymphocytes (PBL) and their subpopulations. PD1 (programmed death receptor 1) and PDL1 (programmed death receptor ligand 1) expression in tumor tissue can also be important for predicting IT efficiency. The most promising predictive biomarker meaning the most clinically relevant is a combination of the PBL subpopulations study and PD1 and PDL1 expression on the tumor cells.

PubMed, Scopus, Web of Science, eLibrary, Russian Science Citation Index databases were searched for the available appropriate literature reports. The authors included 82 in the given review.

CAR-Т cell therapy with the use of cytotoxic lymphocytes with chimeric antigen receptors occupies an important place among modern approaches to the cancer treatment. This therapy has established itself as an effective method of the treatment of CD19+ acute lymphoblastic leukemia. Nevertheless, the recurrences of the illness are not uncommon; the treatment of solid tumors with genetically engineered lymphocytes shows modest results and it is accompanied by the high toxicity. One thing, however, is certain: CAR-Т cell therapy has great potential in the treatment of cancer and further improving of the structure and functions of genetically engineered lymphocytes with chimeric Т cell receptors help greatly increase the efficiency of antitumor treatment.

The review includes the current data on the structure of chimeric lymphocytes of different generations and the trends in improving CAR-Т cell therapy. It includes also the fundamental platform for formation of ideology of use CAR-Т cells for the treatment of solid malignant tumors.

The modern Wilms tumor treatment protocols used all over the world can cure up to 90 % of children. Such successes make it possible to actively introduce risk-adapted therapy methods aimed at de-escalating the chemotherapy regimen and radiation therapy impact to the tumor. The most conservative was the stage of surgical treatment, implying the organ-depleting nature of the surgery. Nevertheless, over the past decade, a lot of experience has been accumulated with both nephron-sparing and minimally invasive interventions in patients with both bilateral and unilateral Wilms tumor.

We presented the experience of laparoscopic kidney resection with intraoperative ultrasound control in a child with unilateral Wilms tumor, receiving treatment at the N.N. Petrov National Medical Research Center of Oncology.

Diagnosis of skin melanoma (SM) in children is a complex clinical and morphoimmunological problem. The rare occurrence, difficult interpretation of histological and immunohistochemical picture explain the error rate in the diagnosis of SM reaching 28.8 %. This article presents a clinical case of false-positive diagnosis of SM. As a result of a detailed assessment of the anamnesis, examination, revision of histological preparations and conducting an immunohistochemical study in the reference center, the diagnosis of SM was excluded.

The basis of modern high-effective therapeutic programs for pediatric lymphomas is an intensive, risk-adopted therapy, which complicated with myelosuppression. In myelotoxic agranulocytosis condition infectious complications are often and its treatment results depend on duration and level of agranulocytosis, and sensitivity of microorganism to antimicrobial agents. Multi-drug resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii and etc. are a serious problem in supportive care of postchemotherapy complications, when even multidisciplinary approach with pediatric oncologists/hematologists, microbiologists, clinical pharmacists, surgeons, specialists in extracorporeal blood purification modalities and intensive care are ineffective.

In spite of a relatively good prognosis of most patients with nephroblastoma, there are some subgroups characterized by different unfavorable prognostic factors, in which the overall prognosis is much worse. In particular, this can be applied to patients with very high risk relapse. As in these cases the tumor is often resistant to most chemotherapy modalities, the quality of surgical control is of utmost importance.

We present a case of a 9-year-old patient with second local nephroblastoma relapse involving a large portion of inferior vena cava. During the course of complex therapy a radical surgical resection with vascular plastic by xenopericardium implant was performed. The follow-up, albeit short, yields no signs of disease progression or graft malfunction.

This case demonstrates the possibility of successful vascular plastic in a child with relapsed tumor. This method may allow more radical tumor resection.

This work is devoted to the analysis of problems associated with reproductive system disorders 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 reproductive system, treatment and prevention are described. Issues of female and male reproductive health are analyzed separately.