Сегодня на вопрос коллег из Хабаровской краевой детской клинической больницы отвечает директор Института гематологии, иммунологии и клеточных технологий ННПЦ ДГОИ им. Дмитрия Рогачева проф. Алексей Александрович Масчан.

Estimation of late effects at children underwent hematopoietic stem cell transplantation (HSCT), development of complex rehabilitation and prophylaxis measures is the actual task of pediatric hematology-oncology. Iatrogenic pathology associated with transplantation affects majority of organs and systems and decreasing of quality of life of child. Most frequently occurring late effects revealed in children after HSCT, grouped by the influence on organs and systems of child, are showed in this review. It was shown that the biggest attention must be paid to immune mediated late effects, questions of immune reconstitution and damage of cardio-vascular, respiratory and musculoskeletal systems, secondary metabolic syndrome. It was marked that due to new approaches to HSCT (total body irradiation, lymphodepletion, post-transplant cell therapy, etc.) special attention must be paid to questions of affecting of immune system of child. Important problem is the development of neurocognitive and psychological deficits. Post-transplant observation of patients must include medical, neurocognitive, academic, psychological and social help to overcoming obstacles of transplantation. Thus, preparation of national clinical recommendations for late effects and HSCT must be done. These recommendations will be the base for collaborative work of transplant and rehabilitation centers.

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.

Rationale. Hematopoietic stem cell transplantation (HSCT) providing possibility to cure malignant oncohematological diseases, selected solid tumors and autoimmune disorders. Aim of review is summarizing of major data on development and perspective of HSCT, studying of new possibilities and developing alternative technologies improving effectiveness of anti-leukemia potential of allogenic HSCT (allo-HSCT) and, at the same time, decreasing of risk of severe complications.

General statues. Allo-HSCT as a method of immunotherapy contributes prolonged remissions, but still limited transplant related morbidity and mortality due to toxic effects on body, infection complications and “graft-versus-host” disease (GvHD). Different methods decreasing side effects of HSCT have been developed. One of the major recent achievements are the successes in haploidentical transplants, which based on the new approaches of GvHD prophylaxis and became accessible almost for all suitable patients and do not concede of standard alloHSCT on efficacy and safety. Allo-HSCT after reduced intensity conditioning or non-myeloablative conditioning for treatment of elderly or weakened patients with advanced stages of hematological malignant disorders have successfully implemented. It was shown how the new technologies enhancing effectiveness of anti-tumor potential allo-HSCT and simultaneously decreases the risks of severe complications. Own experience of allo-HSCT at 19 patients presented. It was shown in our study that allo-HSCT did not improved outcome for refractory/ relapsing patients with acute leukemias, but can be successfully used in remission phase.

Conclusion. Role of stem cells in treatment of haematological and non-hematological malignant diseases (as well as some autoimmune disorders) continuously growing. Comprehensive knowledge on possibilities of usage of transplant technologies, modern methods of cell therapy of leukemias allows to decrease drug toxicity and improve the patients’ outcomes.

Treatment results of hematopoietic stem cells transplantation (HSCT) with myeloablative (MAC) and reduced intensity (RIC) conditioning regimen in children and adolescents with myelodysplastic syndrome (MDS). Fifty seven patients aged 1to18 years who received allo-HSCT from 1996 to 2016 (30 patients with MAC and 29 patients with RIC) are included in the study. Analysis of overall and event-free survival in both groups showed comparable efficacy. The use of RIC as alternative conditioning regimen in children and adolescents with MDS.

Data on estimation of genetic polymorphism thiopurine methyltransferase (ТРМТ) at 97 children of different ages with acute lymphoblastic leukemia (ALL) presented. Studied frequency characteristics of TPMT genotypes: *1 – 90.7 %, *3A – 8.3 %, *3C – 1.0 % comparable with published data. During the analysis of connection of genetic polymorphism TPMT c toxicity of treatment on ALL-MB-2002 protocol it was established significant predominance of severe hematological toxicity at heterozygous patients with mutant alleles in comparison with “wild type” patients. Increasing of severe neutropenia on consolidation stages showed in case of genetic polymorphism of TPMT. Genetic polymorphism did not affect results of ALL treatment. Correlation between TPMT polymorphism and second cancer established.

The article represents the role of high-dose chemotherapy following autologous hematopoietic stem cell transplantation for Hodgkin lymphoma and summarizes the results of 10-years’ experience of high-dose chemotherapy following autologous hematopoietic stem transplantation cell for Hodgkin lymphoma in N.I. Pirogov National Medical and Surgical Center. 5-year overall survival was 63 %, 5-year progressivefree survival – 84 % that corresponds with international data. Complete response before high-dose chemotherapy following autologous hematopoietic stem cell was the main independent prognostic factor of transplantation efficacy. transplantation.

This article represents results of work of Center of pediatric oncology and hematology of Regional pediatric clinical hospital № 1 of Yekaterinburg on Hematopoietic stem cell transplantation (HSCT) during the period 2006–2016. One hundred seventeen HSCT performed during this time including 70 autologous, 33 allogenic, 14 haploidentical at patients with solid tumors (n = 55), acute leukemias (n = 27), lymphomas (n = 9), non-malignant diseases (n = 11). Results of treatment depending on type of disease and HSCT were shown. It was indicated that presence of minimal residual disease (MRD) before HSCT in case of leukemia and neuroblastoma was indicated as negative prognosis. Possible way of treatment of persistent MRD after HSCT with the help of blinatumomab and donor lymphocytes infusion showed.

Personal opinion concerning ideas of Jeffry A. Siegel et al which were published in previous issue of the Russian Journal of Pediatric Hematology, Oncology and Immunology, presented in this article. The essence of the judgment of Dr. Siegel and co-authors is that the linear model with trigger values and ALARA (As Low As Reasonably Achievable) principle can bring more harm than benefits in case of diagnostics in the limits of low dose irradiation.

Authors tend to agree with opinion proposed by Jeffry A. Siegel that blind following of ALARA principle without estimation of dose sizes could block the therapy process and increase the radiophobia both at physician prescribing diagnostics, and relatives of children with a history of long treatment. Herewith, there can be situations when radiophobia can led to limitation of required diagnostic procedures. Taking into account high severity of oncological patients, consequences can be very negative.

Meanwhile authors think that performing of evaluation studies on structure pf dose load in pediatric hematology-oncology required. It is important to observe and foresee the situations in which the excess of low doses possible and to limit the following dose accumulation in this case if clinically possible.