Choroid plexus carcinoma (CPC) is a rare malignant tumor arising from the epithelium of the choroid plexus of the brain. More than 80 % of CPCs occur in children. Mutations in the TP53 gene is played the main role in the pathogenesis of these tumors. Choroid plexus carcinomas in 40 % of cases are associated with Li–Fraumeni syndrome. Survival rates in patients with CPC and Li–Fraumeni syndrome are extremely low. The standards of the therapy for patients with CPC are not defined. The extent of surgical resection and treatment modality correlate with prognosis. The role of adjuvant therapy in CPC remains unclear: doses and volumes of radiation therapy (RT), combinations of chemotherapeutic drugs, timing, and a combination of RT and chemotherapy (CT) have not been identified. Also, there is neither a standard CT regimen nor a prospective international study assessing the efficacy and toxicity of various combinations of cytostatics in patients with CPC. The article presents an overview of the existing molecular genetic changes, existing methods for the diagnosis and treatment of choroid plexus carcinoma.

The main pathogenetic mechanism of the development of pediatric low grade gliomas (pLGGs) is genetic aberrations in BRAF gene. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. We analyzed the clinical and molecular characteristics of 69 patients with LGGs. Molecular genetic testing for BRAF V600E mutation was performed by allele-specific real-time PCR and Sanger sequencing. BRAF V600E mutation was detected in 15 (21.7%) patients with LGG. The majority of BRAF-mutated cases of LGGs had the midline location: OPG – 7, subcortical ganglia – 1, brainstem – 2. The 2-year PFS was much worse in patients with BRAF V600E compared to patients without this mutation – 30% and 66.2%, respectively. The median time to progression for patients with BRAF V600E mutation was 9.5 months compared to 3.1 years for patients without indicated substitution. 5 patients with BRAF V600E-mutated LGGs who experienced progression after the conventional treatment, received targeted therapy (BRAF-inhibitor-3, BRAF + MEK inhibitors – 2) with good response (complete response – 2, partial response – 3). BRAF V600E mutation contributes to poor outcome in patients with LGGs Targeted therapy could be effective in this cohort of patients.

Correspondence: Ludmila I. Papusha Cand. of Sci. (Med.), Senior Physician, Head of the Department of Optimization of CNS Tumor Therapy, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of Russian Federation Address: 1 Samory Mashela St., Moscow 117997, Russia E-mail: ludmila.mur@mail.ru DOI: 10.24287/1726-1708-2020-19-4-58-65

This article describes the use of allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of a patient with metastatic alveolar rhabdomyosarcoma. The reported case is unusual in terms of its presentation, diagnosis, and choice of treatment. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. In the last decades, the survival rates of patients with metastatic malignant neoplasms, including those with soft-tissue sarcomas, have not improved significantly. The prognosis for these patients remains extremely poor despite the intensification of chemotherapy and the application of radiation therapy. The use of autologous HSCT has not brought about any positive changes in treatment outcomes. Experimental approaches to treatment, including immunotherapeutic techniques, aimed at improving the prognosis for very high-risk patients are currently under development. We chose to report this case because of the unconventional treatment approach that had helped to achieve long-term control over the disease and to prevent systemic progression. It demonstrates that allogeneic HSCT can be regarded as one of the promising options for treatment intensification mainly due to the “graftversus-tumour” effect. The patients' parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

Low grade gliomas (LGG) constitute 35-40% of all primary central nervous system (CNS) tumors in children, at least 10-12% of them affecting the optic pathway. The complexity of the localization and predominantly the diffuse type of growth of these tumors make the neurosurgical treatment not appropriate in most cases, which requires conservative treatment. Objective: to analyze the results of carboplatin and vincristine chemotherapy (CT) regime in children with optic pathway gliomas (OPG). The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. In the study was included patients registered at the Burdenko Neurosurgery Institute from January 1, 2003 till December 31, 2015 with optic pathway glioma from 0 to 18 years old that were treated with combined carboplatin and vincristine chemotherapy. All patients were divided into 2 groups: the first group included patients who had newly diagnosed OPG (group 1), the second group included patients with OPG with radiological progression following observation times (group 2). Evaluation of the response to treatment was carried out on the 24th week and after completion of treatment by delineation of each slice of the MRI images in OsiriX MD software (© Pixmeo Sari, Switzerland) with subsequent automatic volume calculation. Results: 104 patients were included in the analysis. 69 children were included to group 1, 35 patients in group 2. 60% of patients were boys, about a third of children were less than 18 months old, 17% of patients had Neurofibromatosis type I, 24% of patients had diencephalic cachexia. A biopsy of the tumor was performed in 76% of the patients, 54% of the patients had a piloid astrocytoma and 23% had a pilomixoid astrocytoma. The progression after the start of the chemotherapy was in 30 (28.9%) patients. 5-year event free survival (EFS) and overall survival (OS) were 58 ± 6% and 97 ± 2%, respectively. 5-year EFS was not statistically significantly different in patients of groups 1 and 2. According to our data, the age, histology of the tumor, the response to the 24th week of CT are independent prognostic factors.

Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21) has very unfavorable prognosis when treated according as standard risk group, mainly due to high risk of relapce. The outcome is improoving dramatically when the patients were treated as high risk. In our study we analyzed clinical parameters and outcome in children with BCP-ALL and iAMP21 according to trial Moscow-Berlin 2008 (ALL-MB 2008). The majority of patients were stratified in standard and intermediate risk group. Seven years event free survival (EFS) in patients with iAMP21 and without iAMP21 was 0.48 ± 0.24 and 0,87 ± 0,2 respectively with cumulative incidence of relapse 0.41 ± 0.24 и 0.07 ± 0.2. BCP-ALL with iAMP21 needs some changes in current stratification strategy and new approaches to treatment. For faster and accurate detection of iAMP21 evaluation by FISH technique must be applied.

The relapse of acute lymphoblastic leukemia (ALL) in children is still a difficult task. This is due both to the difficulties of achieving a second remission and to the problems of organizing allogeneic bone marrow transplantation (BMT) in those patients who need it. The standard approach is the use of second-line drugs in the regime of high-dosage chemotherapy blocks, but the response rate for this treatment in patients with early relapses remains low and the response time is short. Recently, new drugs with different mechanisms of action have appeared that can give an opportunity for a full remission. The organization of a multicentre study on anti-relapse therapy in the Russian Federation is an urgent task, the solution of which can help in studying new approaches to therapy and in the organization of BMT logistics. This article presents the results of a pilot multicentre study on the treatment of relapses of ALL in children in the Russian Federation. The effectiveness of standard therapy for a group with late relapses and the efficacy and toxicity of interventional blocks with the use of bortezomib, clofarabine, nelarabine are presented.

Development of non-invasive methods of studying of exosomes, containing nucleic acids and specific proteins of tumor cells for screening, early diagnostics and monitoring of tumor growth, is the actual problem of oncology. This is important both for primary diagnostics of malignant diseases and for control of metastatic processes, which are the key moment for control of latent tumor stem cells, starting the proliferation and leading to lethal outcome after years and decades after typing of primary tumor. Exosomes, extracted from the tumor cells of biological fluids, malignant exudates and dendritic cells of oncological patients, are the close copies of receptors, proteins and nucleic acids of initial cells, which have the immune modulating activity and able to represent antigens by stimulating of antigen-specific T-cells answer. Therapeutic potential of exosomes studying now in case of infections, which pathogens persist in cells of immune system (toxoplasmosis, tuberculosis, severe acute respiratory syndrome), tumors, autoimmune and autoinflammatory diseases. Experimental data indicate that exosomes, containing antigens of malignant cells, inhibit tumor growth by induction of T-cell specific immune answer, leading to tumor regression in experimental animal models. Transferring of results of study of therapeutic activity of exosomes from mice to humans is impossible due to difference in immune system of human and mouse. However, usage of exosomes in phase I of clinical trials in different oncological diseases showed that therapy with exosomes is safe, non-toxic, well-tolerated, can effectively be combined with colony stimulating factors, inducting congenital and adaptive immune answer, stabilizing disease and provides prolonged surviving for a number of patients. There are also the opposite data on suppressive effect of exosomes on activity of effector cells and, therefore, possible acceleration of tumor growth. General tendency of development of therapeutic studies largely repeats experience of usage of anti-cancer vaccines and it’s relationship with chemotherapy and target immune therapy of malignant disorders. This review reflects diagnostic and therapeutic options of exosomes tumor cells and possibility of usage in monitoring and treatment of malignant disorders of human.

The biological process of apoptosis of cells accompanied by the secretion of exosomes in the body’s biological fluids has been available for half a century but recently has been improved. It was detected that circulating nuclear and exosomal nucleic acids, MRNA, microRNA, multiple proteins, lipoproteins, and other biological substances circulate in the body fluids in some kind of package formed by the plasma membrane of the host cell. These cells are able to exert a reverse effect on the producer cells; the influence includes presentation of the antigens contained in the exosomes and affecting the immune response, regulation of the intercellular interactions, and carcinogenesis. The review presents data on the study of exosomes of tumor cells and approaches to the application of exosomes in personified combined chemo-exosomal therapy of oncological diseases.

Multidisciplinary approach is widely used worldwide among the specialists of different specialties. Joint efforts of oncologist, hematologist, surgeon, radiologist, pathomorphologist, anesthesiologist, ICU-staff, recreation therapist and other specialists are aimed on treatment of patients with hematological and oncological diseases. This manuscript showed the view of physicians on place of surgery in this complex system. Progress of surgery with the help of endoscopic technique, intraoperational navigation, reconstructive and microscopic technique open the width range of possibilities in diagnosing and treatment of patients. Only harmonious work of all staff members from the moment of patient’s entering to clinic to the successful healing, work of clinical-scientific parties allows to reach good oncological and functional results, to prepare new methods and introduce it to the practical usage. This will allow the early social adaption of children and adolescents.

MLL is involved in fusion genes with more than 100 partner genes, approximately 80 of which have been characterized at the molecular level. MLL fusion genes are often found in infants (60-80% of acute lymphoblastic leukemia (ALL) cases and 40-50% of acute myeloblastic leukemia (AML) cases) and are appreciably rarer (8-10%) in children older than 1 year of age. MLL rearrangements are important markers in diagnosis and treatment choice. To identify the partner gene is of primary importance for prognosis and minimal residual disease monitoring. The structure of the fusion gene, including localization of the MLL breakpoints, is also informative. A method was developed to examine the fusion transcripts in order to identify the partner gene among the six most common ones and to establish the exon structure of the rearranged MLL. The method includes a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify and to fluorescently label a fusion transcript fragment and subsequent hybridization of the product on a biological microchip with immobilized oligonucleotides complementary to exons of MLL and its partner genes AFF1, MLLT1, MLLT3, MLLT4, MLLT10, and ELL. Hybridization results were verified by sequencing the RT-PCR products and, in some cases, performing long-distance inverse PCR (LDI-PCR). The study involved 38 bone marrow samples from ALL patients (including 33 children younger than 1 year of age) and 15 samples from AML patients (including 10 from children younger than 1 year of age). The main partner genes were AFF1 (49%), MLLT1 (27%), MLLT3 (12%), and MLLT10 (12%) in ALL and MLLT3 (80%), MLLT10 (10%), and MLLT4 (10%) in AML. Fusion gene transcripts most commonly included MLL exon 11 (58% of ALL cases and 50% of AML cases), suggesting a breakpoint in MLL intron 11.

MLL is involved in fusion genes with more than 100 partner genes, approximately 80 of which have been characterized at the molecular level. MLL fusion genes are often found in infants (60–80% of acute lymphoblastic leukemia (ALL) cases and 40–50% of acute myeloblastic leukemia (AML) cases) and are appreciably rarer (8–10%) in children older than 1 year of age. MLL rearrangements are important markers in diagnosis and treatment choice. To identify the partner gene is of primary importance for prognosis and minimal residual disease monitoring. The structure of the fusion gene, including localization of the MLL breakpoints, is also informative. A method was developed to examine the fusion transcripts in order to identify the partner gene among the six most common ones and to establish the exon structure of the rearranged MLL. The method includes a multiplex reverse transcriptase–polymerase chain reaction (RT–PCR) to amplify and to fluorescently label a fusion transcript fragment and subsequent hybridization of the product on a biological microchip with immobilized oligonucleotides complementary to exons of MLL and its partner genes AFF1, MLLT1, MLLT3, MLLT4, MLLT10, and ELL. Hybridization results were verified by sequencing the RT–PCR products and, in some cases, performing long-distance inverse PCR (LDI-PCR). The study involved 38 bone marrow samples from ALL patients (including 33 children younger than 1 year of age) and 15 samples from AML patients (including 10 from children younger than 1 year of age). The main partner genes were AFF1 (49%), MLLT1 (27%), MLLT3 (12%), and MLLT10 (12%) in ALL and MLLT3 (80%), MLLT10 (10%), and MLLT4 (10%) in AML. Fusion gene transcripts most commonly included MLL exon 11 (58% of ALL cases and 50% of AML cases), suggesting a breakpoint in MLL intron 11.