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Russian Journal of Pediatric Hematology and Oncology

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Vol 10, No 3 (2023)
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FROM EDITION

ORIGINAL STUDIES

11-14 255
Abstract

Background and aims. Immunocompromised pediatric patients with cancer are more susceptible to experiencing severe COVID-19 infection compared to other children. In a global registry study of childhood cancer with COVID-19, involving 1500 patients, severe of critical infections were detected in 20 % of the cases. The mortality rate of 4 % excelled that of the general pediatric population. Data about the development of COVID-19 complications in children with cancer remains limited and varies across different countries. This study aims to describe the incidence and characteristics of COVID-19 infection in children with cancer in Armenia.

Methods. A prospective analysis was conducted on PCR-confirmed cases of COVID-19 infection in children with cancer aged 0–18 years from 2020 to 2022 at the Pediatric Cancer and Blood Disorders Center of Armenia, Yeolyan Hematology Center, the only pediatric hematology/ oncology institution in our country.

Results. Between June 2020 and March 2022, we studied 201 children with cancer in Armenia, of whom 35 cases of COVID-19 infection were confirmed. The median age was 8.4, and the male/female ratio was 1.3. Among the COVID-19-positive patients, 15 had acute lymphoblastic leukemia, 5 had lymphomas, 4 patients had neuroblastoma, and 2 each had medulloblastoma, rhabdomyosarcoma and Ewing sarcoma. There were single cases of osteosarcoma, acute myeloid leukemia and malignant triton tumor. Twenty patients (57 %) were asymptomatic, and the rest presented with fever, sore throat, and cough. Among the patients with hematological malignancies, four developed pneumonia, and two of them experienced cancer progression subsequently. Additionally, four patients had pancytopenia/thrombocytopenia, likely due to the infection with the Omicron in the last three months of the mentioned period. Overall, the incidence of COVID-19 complications was 11 %, and mortality was zero.

Conclusion. This is the first nationwide report on COVID-19 in children with cancer in Armenia. The findings indicate lower rates of severe infection and mortality among compared to global estimates. Further studies are emerging to explore these differences.

15-21 222
Abstract

Glioblastomas are malignant tumors that belong to the central nervous system and are challenging to diagnose due to their significant intratumoral heterogeneity, which makes molecular testing and diagnosis confirmation particularly difficult. In addition to identifying typical genetic mutations such as IDH, H3F3A G34 and K27, WHO recommendations emphasize the importance of analyzing the tumor epigenome to define its class based on DNA methylation patterns and methylation status of specific genomic regions, particularly the MGMT promoter region. Based on our clinical experience, molecular genetic studies sometimes yield contradictory results due to the heterogeneous cellular composition of glioblastomas. In this study, we present a series of observations made on 35 glioblastoma samples in which we compare the morphological features and the results of cell type detection by deconvolution method based on total DNA methylation profiles. Our results suggest that samples of mesenchymal class glioblastomas may contain over 50 % non-tumor immune cells, which should be considered in genetic testing of these tumors.

22-40 516
Abstract

Medulloblastomas of the WNT molecular group (MB-WNT) represent the smallest group of MB and account for only 10 % of the total. This molecular group is characterized by a favorable prognosis. Given the aggressive treatment regimens for MB, reducing the intensity of therapy for prognostically favorable tumors seems justified. Purpose of the study – to demonstrate the results of treatment of children with MB-WNT and to determine the impact on survival of various prognostic factors. The study included 85 patients with MB-WNT under the age of 18 who received treatment and were followed up from 1993 to 2022. Median age at diagnosis was 10 years (min – 3, max – 17). All patients had classical MB. Metastatic spread of the tumor at the time of diagnosis was detected in 18 (21.2 %) patients, the presence of a residual tumor according to postoperative magnetic resonance imaging – in 32 (37.7 %). Somatic mutations in the TP53 gene were detected in 10 (7.1 %) patients, in the CTNNB1 gene – in 79 (92.9 %), in the APC gene – in 5 (5.9 %), chromosome 6 monosomy – in 76 (89.4 %) children. At the time of the analysis, 74 (87.1 %) patients were alive, 11 (12.9 %) patients died, a relapse was diagnosed in 6 (7.1 %) patients, of which 5 died from disease progression, 1 patient is alive in the second remission. One patient in long-term remission developed secondary meningioma 20 years after the diagnosis of MB. The 10-year progression-free survival (PFS) was 0.92. 5-year overall survival (OS) was 0.90, 10-year – 0.86. The median OS is 112 months. When analyzing the sample of patients with MB-WNT in our study, PFS and OS were statistically significantly higher in girls without metastatic tumor spread, with total resection of the tumor, stratified into the low-risk group, and in the absence of a somatic mutation in the TP53 gene in the tumor tissue. In multivariate analysis, PFS was influenced by the stage of the disease and the presence of a somatic mutation in the TP53 gene in the tumor tissue; on OS – only the presence of a somatic mutation in the TP53 gene in the tumor tissue.

41-47 412
Abstract

Introduction. Methotrexate is one of the main chemotherapeutic agents of group antimetabolits, includes in the first line of therapy against osteosarcoma. The drug uses in dose 12 g/m2 according to the protocol EURAMOS-1. The range of methotrexate-induced complications includes renal toxity, hepatotoxicity, myelosuppression, skin and mucosal ulcerations, dyspeptic disorders. One of the formidable, but reversible complications, is methotrexate-induced transient encephalopathy (MIE), the clinical manifestations of which occur in more than 15 % of patients in the treatment of which high doses of methotrexate (HD MTX) are used.

Materials and methods. At the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia the period from 2013 to 2023 10 cases of MIE were recorded. All patients received therapy according to the protocol EURAMOS-1. The 4 out of 10 patients had a delay in the rate of elimination of HD MTX after the course of chemotherapy. No one patient had electrolyte disturbances with using HD MTX. The median occurrence of the complication’s emerging was 7 days (from 5 to 10 from the start of therapy) and most often developed after 3 courses of methotrexate 12 g/m2 , which corresponds in total 6 doses of methotrexate. Neurological symptoms: headache, visual impairment, aphasia, convulsions were transient and resolved after an average of 24 hours from the start of the treatment.

Results. All 10 patients received obligatory alkalization, massive infusion therapy, neuroprotective drugs, as well as decongestant therapy as a treatment of MIE. Subsequently, therapy with methotrexate was continued for the 9 of 10 patients.

Conclusions. The standard recommendations for the treatment of MIE do not currently exist. However, the development of severe neurotoxicity does not exclude the possibility of further using of HD MTX in the treatment program

48-54 223
Abstract

Relevance. The formation of a healthy lifestyle is an important task facing not only the healthcare system, but also the state as a whole. Therefore, monitoring of risk factors and the attitude of the population to a healthy lifestyle is necessary for strategic decisions.

The purpose of the study – assessment of the awareness of the population of Moscow about the importance of maintaining a healthy lifestyle for the prevention of the development of chronic non-communicable diseases.

Materials and methods. A survey of 100 people (50 men and 50 women) aged 20 to 60 years was conducted. The attitude of the population to a healthy lifestyle, alcohol and tobacco use, the frequency of sports, resistance to stressful situations, as well as to periodic medical examinations were evaluated.

Results. The data of the survey, as well as the growing incidence, confirm the irresponsible attitude of the population to their health, as well as the identification of risk factors for the development of chronic non-communicable diseases in a large number of patients.

Conclusions. To form a unified preventive environment, it is necessary to improve the quality of the environment, working conditions, the availability of food of proper quality, income levels, housing conditions, as well as to develop urban infrastructure. It is also important to understand that in addition to the participation of all branches of the state in the formation of preventive medicine, it is necessary to instill in the population the need to take care of their own health independently. Rational nutrition, physical activity (walking, running, sports), restriction of alcohol and tobacco use, create a healthy behavior model and, as a result, reduce the risk of developing non-communicable diseases.

55-62 263
Abstract

Hematopoietic stem cell transplantation (HSCT) is a treatment method for a number of severe malignant and non-tumor diseases. Autologous (auto) and allogeneic (allo) HSCT improves outcomes in patients with solid and hematological malignancies. The toxicity of conditioning regimens before HSCT is often a limiting factor for successful transplant outcomes. The most common manifestations of visceral and tissue toxicity are epithelial (dermatological and mucosal) toxicity, hepatotoxicity, and neurotoxicity. Reducing the incidence of toxic complications of preparative regimens preceding HSCT is the optimization of accompanying therapy, and and individualized selection of doses of chemotherapy. In our study, among 119 HSCT cases performed in 2021–2022, treosulfan-containing preparative regimens were used. Dermatological toxicity was diagnosed in 80.0 %, mucositis – in 100 %, hepatotoxicity – in 18.5 % of observations, no neurological toxicity was recorded.

LITERATURE REVIEWS

63-69 220
Abstract

Clinical heterogeneity appears to be one of the most characteristic feature of the group of peripheral neuroblastic tumors, ranging from spontaneous tumor regression to a widespread process, often resistant to multimodal therapeutic strategies. Despite significant progress in treatment, about 40 % of patients with high-risk neuroblastoma die from disease recurrence after complete response to first-line therapy. These 40 % are considered a “extremely high” risk group requiring intensification of therapeutic regimens from the time of diagnosis. Histological and molecular predictive features of this group are of high scientific and practical interest for the correct therapy.

CLINICAL CASES

70-81 2535
Abstract

Ewing’s sarcoma (ES) of the kidney is an extremely rare malignant tumor characterized by an aggressive course, and therefore the disease has an unfavorable prognosis. Due to the rare occurrence, standards for the treatment of ES of the kidney have not been developed; an integrated approach is often used in therapy. In this article, we present a description of two clinical cases of kidney damage with ES in patients aged 10 and 16 who were treated at the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. In the first case, there was a metastatic lesion of the kidney with the localization of the primary focus in the pelvic bones, in the second, primary ES of the kidney was diagnosed. Both patients had stage IVb at the time of diagnosis (TNM classification American Joint Commission on Cancer). In both patients, after induction chemotherapy, a complete therapeutic response (complete therapeutic pathomorphosis) was obtained. In an integrated approach, in addition to standard chemotherapy, surgery and radiation therapy, in both cases, high-dose chemotherapy with autologous peripheral stem cell transplantation was used, which made it possible to create favorable conditions for long-term remission in one of the patients, even despite the initial prevalence of the process.

82-88 178
Abstract

Introduction. Retinoblastoma (RB), a malignant neoplasm, is the most common pediatric intraocular tumor worldwide. With the advent of intra-arterial chemotherapy, interventional surgeons have assumed a central role in the treatment of this pediatric disease. Intra-arterial chemotherapy is a new treatment modality for RB in which chemotherapeutic agents are precisely delivered into the ocular artery, minimizing systemic toxicity. This procedure has shown impressive results and has significantly reduced the rate of enucleation in advanced and refractory RB. However, the procedure entails potentially serious acute respiratory and hemodynamic disturbances.

Purpose of the study – present our experience with and features of anesthesia management in the development of life-threatening conditions during superselective intraarterial chemotherapy (SIAC) in two patients with RB.

Materials and methods. We present clinical cases in 2 2-year-old patients with RB who received three courses of SIAC for RB with development of severe trigeminocardial reaction.

Conclusion. SIAC is one of the new promising treatments for RB. Prominent cardiorespiratory complications are frequently observed during general anesthesia for repeated sessions of SIAC and can be potentially life-threatening. Presumably, these complications represent an autonomic reflex response to ocular catheterization. Therefore, all patients with RB who are scheduled for SIAC should be included in the high-risk group. The timing of occurrence of the trigeminocardiac reflex is predictable and temporary, but the anesthesiologist must be prepared to treat the developed complication with the help of emergency drugs (adrenaline).

89-100 333
Abstract

Introduction. Hereditary disorders in the DNA repair system can lead to the development of malignant neoplasms in childhood. DNA constitutional mismatch repair deficiency syndrome (CMMRD) is a very rare genetic autosomal recessive disorder caused by homozygous mutations in one of the four mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). The frequency of occurrence is 0.0000001 of the adult and child population. For now about 150 observations have been published in the world literature. The prognosis for CMMRD syndrome is extremely unfavorable. The spectrum of tumors that make up the CMMRD syndrome is very wide, and includes mainly malignant brain tumors, tumors of the digestive tract, hematological malignancies, embryonic tumors, all of which develop in childhood.

The purpose of the study is to report a case of CMMRD-associated embryonic rhabdomyosarcoma in a 3-year-old child.

Conclusions. A review of the literature and the clinical case we have described show that rhabdomyosarcoma belongs to the tumor spectrum of the CMMRD syndrome. An immunohistochemical study revealed an isolated loss of PMS2 gene expression. Taking into account the clinical course of the CMMRD syndrome, a thorough study of the family history in patients with rhabdomyosarcoma is recommended, as well as a molecular genetic study, including the search for germinal mutations in genes in the DNA repair system and the assessment of microsatellite instability in the material of the tumor tissue. The clinical symptoms of CMMRD syndrome are nonspecific and depend on the morphological variant of the primary tumor. Distinctive molecular genetic features of this syndrome are: homozygous mutations with loss of function of the germline genes of the MMR system (mismatch repair) (MLH1, MSH2, MSH6 or PMS2).

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ISSN 2311-1267 (Print)
ISSN 2413-5496 (Online)
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