Dmitry Rogachev National Medical Research Research Articles

An autoinflammatory disease – PFAPA syndrome: a single-center experience

The aim of this study was to analyze the clinical and laboratory data of 101 patients (61 boys, 40 girls) diagnosed with PFAPA syndrome. The age of onset of PFAPA syndrome ranged from 8 to 36 months (the median age of onset was 18 months). The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. In most cases, clinical manifestations included recurrent fevers, acute tonsillitis (in 84% of cases, the tonsils were covered with a whitish coating), and cervical lymphadenitis. More rarely, the patients had diarrhea, vomiting, myalgia, arthralgia, and rash. All of the patients met the criteria proposed by G.S. Marshall. Our management strategies for patients with PFAPA syndrome include symptomatic treatment with antipyretics, short-term glucocorticosteroid therapy, and tonsillectomy. The majority of patients have complete resolution of PFAPA symptoms by the age of 7 regardless of the type of therapy.

Germinal and somatic genetic variants of NF1 in neuroblastoma: own experience and literature review

Introduction. Neuroblastoma (NB) is the most common embryonic extracranial malignant neoplasm in children. The contribution of the NF1 gene to the development of NB is discussed in the literature, but there is no evidence of the pathogenetic role of NF1 gene aberrations in NB. According to various literature sources, the occurrence of pathogenic variants in the NF1 gene in the general cohort of patients with NB does not exceed 1–6 %.Materials and methods. The molecular genetic examination by next generation sequencing (NGS) was performed in 77 patients with NB during the period from April 2019 to July 2021 in the Laboratory of Molecular Oncology Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology. The staging of patients was carried out within the framework of the international staging system, stratification into risk groups and therapy according to the protocol of the German Group for the study of NB GPOH NB-2004. International criteria of the response assessment system for patients with NB were used to assess the response to treatment. Calculations of event-free and overall survival by the Kaplan–Mayer method for the follow-up period up to 12.01.2022 were performed.Results and discussion. The cohort of patients included in the study was represented by patients with an initially unfavorable prognosis. Patients were divided into 3 groups: without pathogenic variants in genes belonging to the RAS-RAF-MEK pathway and TP53 – “RAS-/ TP53-” (n = 43), with clinically significant variants in the NF1 gene – “NF1+” (n = 12), clinically significant variants in the genes of RAS-RAF-MEK and TP53 pathway – “RAS+/TP53+” except NF1 (n = 22). The median age for the entire group of patients at the time of diagnosis was 41 months (0.1–173 months). Boys prevailed over girls with a ratio of 1.5:1. Patients with stage 4 of the disease according to the INSS classification prevailed – 81.8 % (63/77), high-risk groups according to the NB-2004 protocol – 77.9 % (60/77).In our study 13 clinically significant variants in NF1 were identified in 12 patients (15.6 %), of which 4 were germinal, 9 were somatic. The frequency of detection of pathogenic aberrations in the NF1 gene was much higher than the literature data, which can be associated with a selective cohort of studied patients with an unfavorable prognosis and patients with suspected hereditary genetic syndrome. The presentation of adverse events was observed in 83.3 % of patients, more often against the background of specific therapy (in 60 % of cases), which may be due to the rapid acquisition of NB chemoresistance, among other things. When comparing the three groups, it was shown that the frequency of objective responses to induction therapy was statistically significantly lower in the group of patients “NF1+”, when compared with other groups (p = 0.015; p = 0.024), which may also indicate the chemoresistance of NF1-aberrated NB. When analyzing survival there was no statistical difference between the compared groups.Conclusions. The data obtained by us do not allow us to consider the presence of genetic variants in NF1 separately as a prognostic factor, however, it can be assumed that a group of patients with an unfavorable prognosis may be enriched with cases with mutations in the NF1 gene. Refractory course of the disease/development of adverse events in the presence of genetic variants of NF1, causing the activation of the RASRAF- MEK signaling pathway, leads to the induction of tumor chemoresistance. The presence of clinical significance of aberrations in the NF1 gene does not lead to a statistically significant difference in prognosis when compared with patients with aberrations in other components of the RAS-RAF-MEK pathway, however, longer catamnestic follow-up of patients is necessary.Currently, there are no effective drugs for the treatment of NF1-associated NB in clinical practice that requires further study of the mechanisms of chemoresistance development in such patients. Understanding the molecular and genetic features of the course of NF1-associated NB can become the basis for the development of personalized therapy in the future.

The THROMB-HEM study: first results and future prospects

THROMB-HEM is an observational research study discovering the prevalence, risk factors and features of the course and therapy of deep venous thrombosis (DVT) in children with hemoblastosis and bone marrow aplasia which was conducted on from 2012 to 2017 on the basis of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Aim: assessment of the DVT prevalence in children with hemoblastosis and and bone marrow aplasia based on the results of the THROMB-HEM study. The cumulative incidence rate (CIR) of objectively confirmed DVT, symptomatic (sDVT) and asymptomatic (aDVT) DVT in was assessed in children hospitalized in the center from 01.01.2013 to 12.31.2017 in order to verify and treat various hemoblastosis and bone marrow aplasia. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Data from 1623 patients were included for CIR DVT analysis. Among the patients included in the event analysis, DVT was detected in 361 children (285 aDVT and 73 sDVT, in 3 cases there were no data on the clinical picture of DVT). The maximum patient observation time was 5 years. The median follow-up time for patients was 332.15 days (95 % confidence interval (CI) 295.65–379.60). At the third year of follow-up, CVR DVT was 34.8 % (95 % CI 31.3–38.7), CVR aDVT was 28.9 % (95 % CI 25.7–32.5), while sDVT was 8.2 % (95 % CI 5.8–11.5). Unlike aDVT, most sDVT occurred within the first 6 months of therapy. DVT, mostly aDVT, is a common finding in children receiving inpatient treatment for hemoblastosis and bone marrow aplasia, which dictates the need for further research to assess risk factors and the effectiveness of therapy and prevention of these complications.

The use of adoptive cell therapy for the treatment of SARS-CoV-2 in a patient after allogeneic hematopoietic stem cell transplantation

The COVID-19 pandemic continues to be a major public health threat worldwide. The course of this disease in immunocompromised patients is significantly different from that in healthy subjects, which is associated with the impossibility of virus elimination through their own adaptive immune response. Delayed immune reconstitution after hematopoietic stem cell transplantation (which may take months after the procedure) increases the risk of life-threatening COVID-19 infection necessitating a search for and application of new methods of treatment. T lymphocytes are critically important for viral infection control, and are necessary both for the direct elimination of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Low-intensity therapy cures over 40 % of children with rapid Flow-MRD responding ALL: the ALL-MB 2008 trial results

Serious side effects occur during therapy for childhood acute lymphoblastic leukemia (ALL), and survivors can experience long-term consequences. This study aimed at identifying patients who can be successfully treated with low treatment intensity combining clinical parameters and minimal residual disease (MRD) measurements. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. ALL-MB studies used reduced-intensity therapy from the beginning, for standard risk (SR) patients no cyclophosphamide, a very low daunorubicin dose, no high dose of methotrexate, no cranial irradiation. In the ALL-MB 2008 study, 1702 children (49.1 % of all patients) were classified as SR due to favorable initial characteristics. These included 295 patients treated in institutions who took part in a pilot study on MRD measurement using flow cytometry on day 15 and/or at the end of induction (EOI). The most suitable time point for MRD measurement was EOI with threshold 0.1% in 90.5 % of the patients with excellent results: event-free survival of 95 % and overall survival of 97 %, that identified the large proportion of patients (more than 40 % of all ALL patients). The outcome of children with slower MRD response was significantly worse. Initial SR characteristics plus one single MRD measurement at EOI identify more than 40 % of all children with ALL who can be successfully treated with low-intensity regimens as used in the MB protocols.

Nasopharyngeal carcinoma in children and adolescents: a literature review and our own data

Nasopharyngeal carcinoma (NPC) is one of the few epithelial tumors that regularly occur in the pediatric population. The majority of patients with localized and locally advanced NPC can be cured with current treatment protocols which include platinum-based induction therapy followed by chemoradiation therapy. The prognosis of patients with initially metastatic NPC and recurrent disease after prior curative treatment is, however, still unfavorable. Fortunately, new treatment options such as immune checkpoints inhibitors and supportive treatment with oral fluoropyrimidine give hope for better outcomes in these patients as well. It's important to note that the management of NPC diagnosed in adults and children allows for the adaptation of effective treatment approaches for either of the age groups. An analysis of our own data suggests that current treatment protocols for NPC can be successfully adopted by Russian clinics and can help to achieve treatment outcomes comparable to the results obtained in other countries. The purpose of this article is to overview current therapeutic approaches for NPC and possible ways of their improvement based on our own and literature data. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.

Humoral and T cell immune responses over time following SARS-CoV-2 vaccination

In this study, we explored the development and durability of humoral and T cell immune responses among the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology staff members after vaccination with Sputnik V vaccine during the rapid spread of the novel coronavirus disease (COVID-19). The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Three weeks after the first dose of Sputnik V vaccine, anti-spike antibodies were detected in 78.0% of the study subjects. Three weeks after the second dose, anti-spike antibodies were found in 98.4% of the subjects. Three months later, the percentage of the study subjects with anti-spike antibodies fell to 82.7 %. At first, the median antibody level increased from 198.0 BAU/mL (prior to the second vaccination) to 1050.0 BAU/mL (3 weeks after the second dose of the vaccine) but then decreased to 710.7 BAU/mL by 3 months after the full vaccination. Six months after the full vaccination, spike-specific antibodies were detectable in 82.5 % of the studied samples; the median antibody level dropped significantly (to 253.0 BAU/mL). The majority of the study subjects had SARS-CoV-2-specific T cells. They were detected in 71.9 %, 73.9 % and 67.4 % of the subjects at 3 weeks, 3 months and 6 months after the completion of the vaccination course, respectively. The level of S-specific T cells reached a peak at 3 weeks after the vaccination and was found to decline at later time points. Thus, 6 months after the vaccination with Sputnik V, we observed a reduction in both humoral and T cell-mediated immune responses, and this should be taken into consideration when implementing COVID-19 infection prevention and control measures among the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology staff members.

Experience in the use of 5-azacytidine, bortezomib and valproic acid for the prevention of leukemia relapses in children after ab-T cell-depleted hematopoietic stem cell transplantation

Experience in the use of 5-azacytidine, bortezomib and valproic acid for the prevention of leukemia relapses in children after ab-T cell-depleted hematopoietic stem cell transplantation

The potential of impulse oscillometry in lung function assessment in children after allogeneic hematopoietic stem cell transplantation

The article analyzes the potential of using impulse oscillometry in the diagnosis of respiratory disorders in children with oncological and hematological diseases after allogeneic hematopoietic stem cell transplantation (HSCT). The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. A comparative analysis of parameters of impulse oscillometry and spirometry before and on Days 30, 90, 180 and 360 after HSCT was carried out. It was revealed that pulmonary ventilation function impairments are quite common in this group of patients, worsening significantly by month 3 of follow-up. An increase in reactance at a frequency of 5 Hz is one of the earliest signs of impaired respiratory function, which can be used for timely diagnosis of pulmonary complications after allogeneic HSCT.

Analysis of genetic aberrations in pediatric low-grade gliomas: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Low grade gliomas (LGGs) are the most common brain tumors in children. Our retrospective-prospective study of biological characteristics of sporadic LGGs (not associated with neurofibromatosis type I) included 233 patients aged 0 to 18 years who had been diagnosed and/or treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology in the period from 2009 to 2021. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. The median age at the diagnosis was 5 years 4 months (2 months – 17 years). Among the LGGs, the following histological variants were identified: pilocytic astrocytoma (n = 191; 82%), pleomorphic xanthoastrocytoma (n = 16; 7%), ganglioglioma (n = 7; 3%), desmoplastic infantile ganglioglioma (n = 4; 2%), diffuse leptomeningeal glioneuronal tumor (n = 5; 2%), dysembryoplastic neuroepithelial tumor (n = 2, 1%), and diffuse astrocytoma (n = 1; 0,5%). The tumors were located in: the suprasellar region (n = 98; 42%), the brainstem (n = 40; 17%), the cerebellum (n = 35; 15%), the hemispheres (n = 34; 15%) etc. The KIAA1549-BRAF fusion was the most common molecular genetic alteration (n = 107; 46%). The second most frequent genetic aberration was the BRAF V600E mutation (n = 44; 19%). Rare molecular genetic events leading to the activation of the MAPK signaling pathway were detected in 13 (6%) patients. The H3 K27M mutation associated with an aggressive clinical course was identified in three patients with brainstem LGGs (1%). These findings point to the importance of molecular profiling of pediatric LGGs for the selection of an effective strategy for molecular diagnosis and optimal clinical care.

Low specificity of HLA-DR expression for diagnosis of acute promyelocytic leukemia

Contemporary therapy of acute promyelocytic leukemia (APL) is based on the use of all-trans retinoic acid, which is effective against tumor cells harboring RARa gene rearrangements (most common – t(15;17)(q24;q21)/PML::RARa). In several studies, it was suggested to use typical immunophenotypic features of APL (HLA-DR-negativity, etc) for prediction of RARa rearrangements presence. In this study, we aimed to evaluate the range of genetic aberrations that could be found in the HLA-DR-negative acute myeloid leukemia (AML). Our study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Among studied 806 pediatric AML patients, HLA-DR-negativity was found in 253 cases. Only in 45.4% of them t(15;17)(q24;q21)/PML::RARa was found, while in remaining 54.6% normal karyotype or other genetic aberrations without RARa involvement. Frequency of the most common immunophenotypic features of APL, such as total CD117, CD33 and MPO expression with the lack of CD34, was higher in patients with t(15;17)(q24;q21)/PML::RARa, although only two thirds of APL cases were found to have all these signs. Moreover, the percentage of cells positive or negative for mentioned antigens varied significantly in APL group. Thus we can conclude, that all “typical” immunophenotypic characteristics of APL including HLA-DR-negativity, are very unspecific and cannot be used for reliable prediction of presence of t(15;17)(q24;q21)/PML::RARa.

The outcomes of children with acute myeloid leukemia treated in accordance with the AML–MM-2006 protocol

Over the past years, the outcomes of patients with acute myeloid leukemia (AML) have significantly improved due to the use of intensive chemotherapy, more effective supportive therapy, and the availability of allogeneic hematopoietic stem cell transplantation. This article presents the outcomes of children with AML treated in accordance with the AML-MM-2006 protocol. Our study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included 233 patients with a median age of 6.5 years (7 days – 18 years) who were stratified into the following risk groups: standard risk, intermediate risk, and high risk. The 5-year event-free survival (EFS) was 0.64 ± 0,14, 0.49 ± 0.05, and 0.43 ± 0.05 for standard-risk (n = 12), intermediate-risk (n = 106), and high-risk (n = 115) patients, respectively (p = 0.14), while the 5-year overall survival (OS) was 1.0 year, 0.7 ± 0.05 and 0.55 ± 0.05, respectively (p = 0.001). The OS in the entire cohort was 0.68 ± 0.032. Factors associated with poor prognosis included hyperleukocytosis, the presence of extramedullary lesions, and age < 1 year. The overall survival rates in these patient groups were 0.55 ± 0.08, 0.39 ± 0.09 and 0.49 ± 0.08, respectively. The worst prognosis was for patients with monosomy 7 and t(7;12) whose OS rates were 0.25 ± 0.2 and 0.4 ± 0.2, respectively. For non-responders and patients with relapsed AML, the OS was 0.33 ± 0.08 and 0.54 ± 0.06, respectively. Early death (before remission could be achieved) occurred in 4% of patients, and 3.8% of patients died in first remission. Sixtytwo percent of deceased patients died of disease progression. In the entire cohort of patients, the five-year EFS was 0.53 ± 0.047, the cumulative risk of relapse after 3 years of remission was 40%, the confidence interval was 23–89%.

Нарушения вкусовой чувствительности у детей, излеченных от гемобластозов: анализ распространенности и возможных причин

Objective. To study the structure of taste disorders and possible risk factors of their development in children after the end of hemoblastosis treatment. Patients and methods. This retrospective study included data on 54 children who underwent rehabilitation in the Treatment and Rehabilitation Research Center “Russkoe Pole” of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A comparison group was formed of 216 patients with hemoblastosis. Taste sensitivity analysis method: GOST (All-Union State Standard) ISO 3972-2014 (sweet, salty, bitter, sour tastes). Results of the dental examination and consultation with a neurologist, time after the end of treatment, and body composition (body fat and lean body mass) were analyzed. Results. It was found that 64.8% of children had nutritional disorders, 48.1% – excess body fat, 7.5% – severe dysgeusia, 24.1% – impaired sensitivity to three tastes, 24.1% – to two tastes, and 44.3% – to one taste. Ageusia to bitter taste (26%) and hypergeusia to sour taste (20%) were the most common. No significant correlation with the time after the end of treatment was obtained. Conclusion. Statistically significant differences were found between the study group and the comparison group depending on the investigated risk factors. To obtain highly significant results, it is advisable to conduct prospective studies in larger patient groups. Key words: children, taste disorders, malignant neoplasms, hemoblastosis, nutritional status, toxic neuropathy, dental status

Оптимизация алгоритма диагностики, маршрутизации и хирургического лечения новообразований параменингеальной локализации у детей

Objective. To optimize an algorithm for the management of children and adolescents with parameningeal tumors based on a comprehensive assessment of diagnostic and therapeutic efficacy in this type of tumors. Patients and methods. The article presents a retrospective study and prospective evaluation of follow-up of 249 patients who underwent surgical treatment in the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and in the Russian Children’s Clinical Hospital (Pirogov Russian National Research Medical University) from January 2003 to September 2021. The study included 139 patients with juvenile nasopharyngeal angiofibroma, 82 patients with fibro-osseous lesions, and 28 patients with parameningeal rhabdomyosarcoma. The follow-up period was at least 1 calendar month. Results. A comparative analysis of the efficacy of preliminary diagnosis of parameningeal tumors depending on the nosology was described; analysis of patient safety during the intra- and postoperative periods, postoperative adaptation, surgical radicality and survival analysis according to the surgical treatment method was performed; algorithm for the management of patients with parameningeal tumors was described. Conclusion. It is advisable to introduce the algorithm developed by the authors into routine clinical practice to optimize medical care for children and adolescents with parameningeal tumors. Key words: children, tumors, parameningeal site, surgical interventions, juvenile angiofibroma, juvenile ossifying fibroma, rhabdomyosarcoma

Superimposed high-frequency jet ventilation in children with oncohematological diseases and acute respiratory distress syndrome

BACKGROUND: The mortality rate of children with hematological cancer and acute respiratory distress syndrome is still high, which is often associated with the ineffectiveness of traditional mechanical ventilation methods in the treatment of critical hypoxemia in these patients. Currently, the search continues for alternative methods of respiratory support, one of which is the combined high-frequency jet artificial ventilation of the lungs. AIM: This study aimed to evaluate the efficacy and safety of combined high-frequency jet artificial ventilation in the treatment of children with hematological malignancies and severe acute respiratory distress syndrome. MATERIALS AND METHODS: The study was conducted in the Department of Resuscitation and Intensive Care of the Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology, from 2016 to 2020. Combined high-frequency jet artificial ventilation was used as an alternative method of respiratory support. RESULTS: In case of severe hypoxemia caused by secondary severe acute respiratory distress syndrome, the use of combined high-frequency jet ventilation after 12 h leads to a significant improvement in arterial blood oxygenation, improves the biomechanical characteristics of the respiratory system, and reduces the likelihood of developing ventilator-associated lung damage. An increase in oxygenation and absence of an effect on the indicators of central hemodynamics provide a greater delivery of oxygen to the tissues, thereby improving the general condition of the patients. CONCLUSIONS: In severe parenchymal respiratory failure accompanied by critical hypoxemia, combined high-frequency jet artificial ventilation of the lungs can be considered an alternative method of respiratory support.

Orthopedic disorders in children suffering from neuroblastoma with intraspinal extension: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology

Neuroblastoma (NB) is the most common extracranial tumor in children. In 5–15% of cases, the tumor extends into the spinal canal and can potentially cause neurological deficits and orthopedic problems that can develop both at the onset of the disease and at a later time. We analyzed data of 61 patients with NB and intraspinal extension who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology over the period from Jan 2012 to Dec 2018. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. The treatment was delivered in accordance with the NB-2004 protocol. In all the children, magnetic resonance imaging and/or computed tomography of the CNS were performed to evaluate intraspinal extension of the tumor as well as the degree of spinal cord compression. The presence of scoliosis and its severity were determined at the baseline and at 2 years after the diagnosis using imaging data and Cobb angle measurement. Scoliosis was classified as mild if the Cobb angle was 10–25°, moderate if it was 25–40°, and severe if it exceeded 40°. In our study, 7/61 (12%) patients were diagnosed with scoliosis at the baseline assessment. The median age at diagnosis was 8.0 (2.3–11.8) months. The male to female ratio was 2.5:1. In 4/7 (57%) patients, the primary tumor was located in the retroperitoneum (outside the major organs), and in 3/7 (43%) patients – in the posterior mediastinum. In this group, 4/7 (57%) patients had INSS stage 2 or 3 tumors, 2/7 (29%) patients had stage 4 disease, and 1/7 (14%) had INSS stage 4S. The majority of patients (5/7 (71%)) were stratified into an observation group. In 6/7 (86%) patients, the tumor extended into the spinal canal involving the thoracic spine. In 6/7 (86%) cases, there was evidence of complete obstruction of the spinal canal. Neurosurgery was performed in 4/7 (57%) patients. All these patients were diagnosed with mild scoliosis at the baseline. At 2 years after the diagnosis, imaging data were available for 38/54 (70%) patients who had not had scoliosis at the baseline. This time, scoliosis was diagnosed in 9/38 (24%) cases. The median age at NB diagnosis was 8.2 (0.8–42.3) months, the male to female ratio was 2:1. In 7/9 (78%) patients, the primary tumor was located in the posterior mediastinum. The majority of patients were stratified into an observation group (7/9 (78%)). In 8/9 (89%) patients, the tumor extended into the spinal canal involving the thoracic vertebrae. In the majority of patients (4/9(44%)), the tumor filled 33 to 66% of the spinal canal. Neurosurgery was performed in 6/9 (67%) patients. In this group, 7/9 (78%) patients were diagnosed with mild scoliosis and 2/9 (22%) patients – with moderate scoliosis. NB with intraspinal extension can lead to various orthopedic problems including scoliosis that can be revealed both at the onset of the disease and at a later time, meaning that this condition requires a multidisciplinary approach involving orthopedic specialists.

Clear cell sarcoma of the kidney in children: clinical characteristics and treatment results

Clear cell sarcoma of the kidney (CCSK) is a rare malignant renal tumor in children, which accounts for 2–5% of pediatric kidney malignancies. The aim of the study was to analyze the results of therapy of patients with CCSK treated in Dmitry Rogachev National Medical Research Center оf Pediatric Hematology, Oncology and Immunology. Retrospective analysis of patients with a histologically confirmed diagnosis of CCSK treated for the period 01.2012–02.2020 (98 months) was done. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI of the Ministry of Healthcare of the Russian Federation. Demographic characteristics, clinical symptoms, methods of diagnosis, and treatment modalities were analyzed. Patients were treated according to the protocols of the SIOP-RTSG group (SIOP 93-01, SIOP-2001, SIOP-RTSG-2016). The stage was assigned according to the SIOP classification. Overall and event-free survival was assessed by the Kaplan–Mayer method. The analysis of the results was carried out on 01.03.2021. The analysis included 10 patients with CCSK. The median age at the time of diagnosis of CCSK was 30.1 months (range 13.5–70.8 months). All patients were male. The duration from the onset of the first symptoms/detection of the tumor to the diagnosis was 0.8 months (range 0.1–3.2 months). The diagnosis was established on the basis of clinical and radiological data (n = 9) and biopsy (n = 1). Distant metastases at the time of diagnosis were detected in 1 (10%) patient (localization of metastases - lungs). The median tumor volume was 439 cm3 (range 256–996 cm3 ). Preoperative chemotherapy was performed in all patients (AV regimen (actinomycin D, doxorubicin) in 7 (70%) patients). Assessment of response after preoperative chemotherapy showed tumor regression in 3/10 (in 1/7 with AV regimen), tumor progression in 5 and stable disease in 2 patients. Surgical treatment in the extent of nephrectomy was performed in all patients. In 1 (10%) case, intraoperative tumor rupture was documented. Distribution of patients by local stages: I – 4/10 (40%), II – 2/10 (20%), III – 4/10 (40%) (including 1 patient with distant metastases). In 1 patient, a left thoracotomy was performed to exclude lung metastases. Adjuvant chemotherapy was performed in all patients in accordance with the relevant protocols of the high-risk group: 7 – 4–5-drug regimen, 3 – AVD regimen (actinomycin D, vincristine, doxorubicin). Radiation therapy was performed in 6/10 (60%) patients. Outcomes: 9/10 (90%) – alive, 1/10 (10%) patient died (non-tumor-related death). 3-year event-free survival and overall survival were 78.8% (95% confidence interval (CI) 52.5–100) and 90.0% (95% CI 71.4–100) respectively. Intensive program therapy in patients with CCSK allows to achieve satisfactory results of treatment.

Thrombopoietin receptor agonists for the treatment of severe persistent and chronic immune trombocytopenia in children: clinical data of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology

Thrombopoietin receptor agonists (TPO-RA) – romiplostim and eltrombopag – changed considerably the therapeutic options for severe persistent and chronic immune thrombocytopenia (ITP). The article presents the results of a retrospective study of TPO-RA efficacy and safety in patients under 18 years of age. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Sixty-eight children had a total of 89 courses of TPO-RA (44 romiplostim and 45 eltrombopag). Their median age was 6.5 years. The median ITP duration was 15.8 months. All patients received previous ITP therapy (1–6 lines). Before the initiation of TPO-RA, the majority of patients had thrombocytopenia with bleeding. In most cases, the platelet response was achieved within the first 2 months of treatment. The average effective doses of romiplostim and eltrombopag were 10 mg/kg per week and 75 mg per day, respectively. Half of patients in romiplostim group and 62% of patients in eltrombopag group did not require extra therapy. The majority of patients (75.6–81.8%) achieved an overall response, but only near 50% achieved a durable (more than 24 weeks) platelet response. Six patients sustained the response after TPO-RA discontinuation. The most common adverse events (AE) of TPO-RA therapy were transient elevation in hepatic enzymes in eltrombopag group (28.9%) and thrombocytosis (18.2–22.2%) in both groups. In 6 cases the therapy was discontinued due to AEs. Two AEs were serious. Our results demonstrate that TPO-RA could safely increase platelet counts and decrease the risk of spontaneous life-threatening bleeding in nearly half of children with severe persistent and chronic ITP. TPO-RA could help to avoid long-term immunosuppressive therapy and splenectomy or delay them and the ITP remission is possible in some cases.

Incidence of venous thromboembolism in children with primary lymphomas

Cancer increases the risk of venous thromboembolism (VTE) in adults and children. The aim of our study was to evaluate the incidence of VTE in children and adolescents with lymphomas. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A retrospective analysis based on medical data of 262 children and adolescents (0–18 years) with primary lymphomas (n = 262) who were treated in Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology since 01.01.2013 to 31.12.2019 had been performed. Such parameters as age and sex distribution of patients, the frequency, as well as the cumulative incidence of detection (CI) and differences in localization, the median time of detection of symptomatic (sVTE) and asymptomatic episodes of VT (aVTE), their relationship with central venous catheters (CVC) were analyzed. Statistical processing of the obtained data was carried out using the XLSTAT 2020 program (Addinsoft, France). The median age was 11,1 years (interquartile range (IQR) 6.5–15 years), the ratio of males to females was 2.2:1. There were 71 episodes of VTE in 65 patients (24.8%, 95% confidence interval (CI): 19.6–30). Among all episodes of VTE 31% were defined as sVTE at 400 day CI for sVTE was found to be 8.1% (95% CI: 5.4–12.2) and CI for aVTE – 18.7% (95% CI: 14.4–24.2). The median time to VTE episode was 38 days (IQR 16.5–91.5 days). There was a trend towards an earlier diagnosis of sVTE (median 23.5 days, IQR – 17–42 days) than aVTE (median 62 days, IQR 14–80 days), p = 0.075. VTE was CVC-related in 67.7 of all VTE cases. In one case, asymptomatic thrombosis of right atrium led to pulmonary embolism (PE). VTE is a frequent complication in children and adolescents with lymphomas. Most episodes of VTE were asymptomatic, one of which was the most likely cause of PE in the child. Further research is needed to find risk factors for VTE.

Kaposiform hemangioendothelioma/Kasabach–Merritt syndrome. Сlinical and laboratory characteristics. Analysis of clinical cases

Kaposiform hemangioendothelioma (KHE) is a rare, usually congenital vascular tumor. It resembles Kaposi sarcoma histologically, but etiologically it is not associated with herpes simplex virus type 8. KHE refers to tumors of intermediate malignancy degree. The most severe complication is the addition of thrombocytopenia and consumption coagulopathy, i.e. development of the Kasabach–Merritt syndrome/phenomenon (KMS), which determines the high mortality rate (up to 30%) in this histological variant. The frequency of occurrence of KMS is unknown. Over Patients with KHE/KMS have clear clinical and laboratory characteristics, which in most cases allow make to diagnose without histological confirmation. Over 7-year follow-up period 32 patients with KHE were registered in our center; in 90.6% of cases it was complicated by the development of KMS. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. In the most of patients the tumor was detected from birth (84%), in half of the cases (52%) hematological complications were diagnosed simultaneously with the detection of the tumor. Сommon local complications include joint contractures, destruction of bone tissue, and invasion of neighboring organs. The half of the patients had changes in the heart function: from minor cardiac pathology to congenital defects. In addition, there were clinical and instrumental changes associated with volume overload: an increase in liver size, myocardial hypertrophy. Despite the presence of clear clinical and laboratory characteristics of KMS, some cases require differential diagnosis with other vascular anomalies accompanied by thrombocytopenia and consumption coagulopathy – with congenital hemangiomas (rapidly involuting congenital hemangioma), multifocal lymphangioendotheliomatosis with thrombocytopenia, kaposiform lymphangiomatosis, venous malformations. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.