Relevance. The limited selectivity of antitumor therapy for central nervous system neoplasms entails the risk of dental morbidity in patients.The aim of the study is to assess the severity of damage to the dental hard tissues in patients with tumors of the posterior cranial fossa (medulloblastoma, astrocytoma) and other tumors of the central nervous system.Materials and methods. Three comparison groups were established based on the toxicity profiles of antitumor therapy among 251 patients at the "Russian Field" treatment and rehabilitation scientific center, to assess the characteristics of oral health status. The assessment of oral health status included diagnosing the carious process and calculating the DMFT index. The degree of damage to the dental hard tissues was evaluated on a four-point scale. The clinical manifestations of oral cavity pathology were compared using the Z-criterion for multiple pairwise comparisons of data, with adjustments for multiple testing (Multiple pairwise comparison Z-test for proportions with multiple testing correction) using the free R software version 3.5.2. The null hypothesis of equal indicators in the compared groups was rejected with a 95% confidence probability when comparing groups of patients.Results. Dental hard tissue pathology was significantly more prevalent in patients with medulloblastoma compared to those diagnosed with astrocytomas and other central nervous system tumors. Additionally, the prevalence of dental hard tissue pathology progressively decreased as the observation period following the completion of antitumor remission was extended.Conclusion. The most severe damage to dental hard tissues is observed in patients with medulloblastoma, who undergo more intensive antitumor therapy compared to those with CNS tumors of other histological types.

Acute lymphoblastic leukemia is the most common pediatric cancer. The effectiveness of modern therapy protocols makes it possible to cure over 80% of children, and one of the advanced treatment methods is the use of monoclonal antibodies. Using the example of adult patients in the United States, the economic effectiveness of this innovative treatment strategy was proven, while no similar studies have been conducted in children with primary acute lymphoblastic leukemia. The aim of the study was to determine the real cost of therapy for children and adolescents with acute lymphoblastic leukemia according to the protocol using combined chemotherapy and immunotherapy at the stages of induction and consolidation. Materials and methods. The study included data from 54 patients (the study group) who received therapy using this method, taking into account indicators of direct medical and non-medical costs. The control group included 54 patient models corresponding to the initial estimated parameters when planning the protocol (body weight 30 kg, body surface area 1 m2). Research results. The median of real cost for providing medical care to one patient in the study group was 22% lower than the estimated cost. In its structure, the values of the median costs for inpatient stay, for instrumental and laboratory studies, as well as for drug therapy turned out to be lower. Since younger patients were included in the study group, the cost of drug therapy was recalculated to the calculated patient model, which equalized the median cost of drug therapy for the study and control groups. In a situation with equal characteristics of patients, as well as with the same cost of a day of inpatient stay, the median real cost of providing medical care to one patient in the study group corresponded to the estimated values. Conclusions. The median cost of medical care for patients with acute lymphoblastic leukemia according to the protocol using combined chemotherapy and immunotherapy in the study group was 22% lower than the estimated values. The actual practice of using the protocol for an average patient model with an equal cost of inpatient stay fully corresponded to the estimated values of the protocol.

The purpose of work was to determine CECT characteristics of primary juvenile angiofibroma of the nasopharynx and skull base (JNA), as well as determination of the paths of spread for the tumor, search for those of them, which are statistically significantly associated with surgical blood loss of subsequent treatment and search for ways to model possible blood loss on their basis.Materials and methods. The data of 60 patients aged from 8 to 17 years were analyzed retrospectively. All patients were boys. The median age was 14 years. The median duration of the disease at the time of surgery was 7 months. The correlation between each of 45 evaluation criteria and intraoperative blood loss was determined for patients in the study group.Results. CT characteristics of JNA were established. The factors, detected by CECT, statistically significantly influencing intraoperative blood loss in angiofibroma treatment were established. A method for modeling intraoperative blood loss based on imaging data was presented.Conclusion. CT with contrast enhancement allows determining of characteristic radiological signs of JNA as well as its characteristics influencing blood loss during surgical treatment. Based on CT data it is possible to model blood loss potential during the JNA treatment.

Here we report a boy with disseminated choroid plexus carcinoma diagnosed at an age of 2 years 9 months on the background of de novo germline mutation in ТР53. The patient received 3 cycles of high-dose methotrexate-based chemotherapy and 4 cycles of alternating carboplatin/cyclophosphamide chemotherapy, followed by craniospinal proton beam irradiation. To date, the patient lives with neither progression of the disease nor other extracranial neoplasms for 6 years from the diagnosis. This is the first successful experience of proton irradiation therapy affording long-term survival in a child with Li-Fraumeni syndrome-associated choroid plexus carcinoma.

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin’s lymphoma (cHL) is a rare malignant disease that develops from mature B cells. This disease was first recognized as a distinct entity in 2008. It is most common in the 20 to 40 age group and rare in children. Currently, there are no clear criteria for diagnosis and standard therapy for such patients. According to the literature, it is possible to use treatment regimens applied for both aggressive B-cell lymphomas and Hodgkin’s lymphoma. The addition of anti-CD20/CD30 targeted agent to standard therapy may be effective, given the expression of these markers by tumor cells. In this article, we present the clinical and morphological characteristics of patients with unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and cHL, diagnosed at our center, including 4 patients at the onset of the disease in childhood

Introduction. Congenital thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening genetic disorder characterized by recurrent episodes of microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction due to the defi ciency or dysfunction of the ADAMTS13 enzyme. Despite the availability of clinical and laboratory diagnostic criteria the diagnosis remains challenging due to a wide range of diseases with similar appearance.Aim: to analyze the clinical manifestations and treatment results of identifi ed cases of congenital TTP at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.Methods. This article reviews 11 clinical cases with congenital TTP genetically confi rmed or with typical clinical and laboratory signs.Results. Clinical and laboratory signs of TTP are highly variable and nonspecifi c, which was observed in the described cohort of patients. One of the trigger factors is often an acute respiratory viral infection, and stabilization of the disease can occur after transfusions of blood components. A delay of diagnosis can often lead not only to a delay of correct therapy, but also to the prescription of wrong therapy. The main diagnosis confi rmatory method was a molecular genetic test, which was carried out in 8 cases. All patients diagnosed with congenital TTP were successfully treated with FFP therapy.Conclusion. Early diagnosis of TTP is diffi cult due to the lack of specifi c clinical manifestations and easily accessible laboratory tests

Introduction. In Russia, within the framework of the GIPAP program, in the period from 2001 to 2007 at the National Medical Research Center for Hematology, imatinib therapy was initiated in 235 patients in the chronic phase of chronic myelogenous leukemia (CML).Aim: to analyze the long-term results of therapy in patients with CML who started imatinib therapy as part of the GIPAP program.Methods. A retrospective analysis of the results of therapy was performed in 235 patients with СР CML, who received imatinib under the GIPAP program from 2001 to 2007 at the National Medical Research Center for Hematology. The protocols for therapy and monitoring of the residual disease of patients at various time intervals were determined by the clinical recommendations relevant at that time in the conditions of real clinical practice and the possibilities of the patient’s region of residence. Overall survival and survival without discontinuation of imatinib therapy, univariate and multivariate analysis of overall survival were performed. The cumulative incidence of responses was calculated. An analysis of response factors, the probability of death from concomitant diseases and death from CML was carried out.Results. The median follow-up of living patients at the time of analysis was 17.3 years (IQR 15.5–18.5). 70 (30 %) patients died, with the median time to death from the start of therapy being 7.8 years (IQR 3.7–13.6). The overall 10-year, 15-year and 20-year survival rates were 82 %, 74 % and 62 %. The cause of death in 43 cases (61%) was the progression of CML to the phase of acceleration or blast crisis and death out of remission for an unspecifi ed cause. 27 (39%) patients died from causes not related to CML. Patient age at initiation of imatinib therapy, length of time from diagnosis to initiation of imatinib therapy, and Sokal and ELTS risk groups at disease onset were identifi ed as signifi cant for survival by univariate analysis. Multivariate analysis showed independent predictive value for overall survival for age at initiation of imatinib therapy, length of illness before imatinib treatment, and ELTS risk group at disease onset. Among patients who died from CML progression, the proportion of patients who did not achieve CCyR for the entire period of therapy before death was 83% (35/42), while among patients who died from concomitant diseases, the proportion of patients without CCyR for the entire period of therapy was 11 % (p < 0.0001). The median duration of imatinib therapy was 11.4 years (0.8–21 years). 40 people died during imatinib therapy, 103 patients are alive and continue therapy with imatinib, 92 patients received at least one second-generation of Tyrosine kinase inhibitors (TKI) (TKI2), of which 62 people are alive and continue treatment with TKI. No more than two lines of TKI therapy were received by 49 (21 %) patients, and three or more lines were prescribed to 43 (18 %) patients. The median duration of therapy after switching to TKI2 was 7.8 years (0.1–15.6 years). Overall 15-year survival after switching to TKI2 was 59 %. On therapy with imatinib, during the entire observation period, complete cytogenetic response (CCyR) was achieved in 171 patients (73 %), another 18 patients (8 %) achieved CCyR for the fi rst time after switching to TKI2. Major (MMR) and deep molecular response (DMR) were achieved with imatinib in 129 (56 %) and 124 (53 %) patients, with TKI2 TKI2 therapy in 38 (16 %) and 33 (14 %) patients, respectively. Multivariate analysis showed an independent predictive value of only the time period from diagnosis to the start of imatinib treatment for achieving molecular responses to TKI therapy.Conclusion. After 20 years of monitoring patients on TKI therapy, we still cannot say that survival in CML is comparable to the survival of normal population. Long-term follow-up confi rms the fact that tumor reduction to at least the level of CCyR is the most signifi cant surrogate marker associated with a reduced risk of death from CML. Timely diagnosis of the disease, rapid initiation of targeted therapy and the fastest possible induction of cytogenetic and molecular responses is a very important mechanism for reducing the risk of resistant course and progression of CML.

We conducted a retrospective sample study with prospective collection of follow-up 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 of Ministry of Healthcare of the Russian Federation. In the time period from January 2013 to August 2020 (92 months), 126 patients with head and neck soft-tissue sarcomas (STS) received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. We included 25 patients who had undergone surgery for neck STS and divided them into 4 groups (rhabdomyosarcoma (RMS), non-RMS-like STS, RMS-like STS, IRS-IV STS – with distant metastasis at baseline). The median age at the time of correct diagnosis was 2.6 (0.5; 5.0). The median time from symptom onset to the verification of the correct pathomorphological diagnosis was 3.2 (1.6; 4.9) months. We discovered a significant number (13/25, 52%) of cases of biopsy that was performed improperly (excessive/non-diagnostic biopsy, fine-needle aspiration biopsy) at a general inpatient facility. The correct pathomorphological diagnosis was clinically and statistically much more often made at a reference center (20/25, 80%; p = 0.003). Moreover, more than half of pathomorphological diagnoses (8/13, 62%) made at a general inpatient facility were later changed at a reference center. Radical resection was achieved in 17/20 (85%) survivors. In 3/20 (15%) cases, a repeat surgery was not needed because of the patients' complete response to protocol-based treatment. Radiotherapy was carried out in 11/25 (44%) cases. Protocol-based treatment was completed in 19/25 (76%) patients, 18/25 (72%) patients achieved complete response, 2/25 (8%) patients were considered incurable, and 4/25 (16%) children died before the completion of therapy. Post-operative complications of varying severity were observed in 10/25 (40%) cases and were dependent on the degree of STS extension and the severity of the condition of the patients undergoing intensive protocol-based treatment. The median time of patient observation since diagnosis verification was 33.2 (15.6; 74.2) months. The five-year overall survival (OS) was 76.3% (95% confidence interval (CI) 51.8; 89.5), the five-year event-free survival without local disease progression – 73.9% (95% CI 41.8–90.1). Even though there weren't many patients with IRS-IV in our study (4/25, 16%), their exclusion from the analysis resulted in a higher 5-year OS rate: 88.2% (95% CI 60.2; 96.9). This study revealed significant problems in the differential diagnosis of neck STSs in children. In most patients receiving optimal protocol-based treatment, neck tumors can be radically removed at a specialized healthcare facility without mutilating surgery, which results in high 5-year OS and event-free survival rates in patients without distant metastasis. Our findings require further investigation in a larger sample of patients.

Intracranial mesenchymal tumors with rearrangements of the genes of the FET and CREB families were first described in the 2021 World Health Organization classification of tumors of the central nervous system. At the moment, the criteria for the diagnosis and treatment of these tumors have not been unambiguously defined. This article presents two exceptionally rare clinical cases of adolescent patients with IMT with the presence of gene rearrangement of the FET and CREB gene families, who were treated and examined at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The patients’ parents gave consent to the use of their children's data, including photographs, for research purposes and in publications.