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Aim. To determine predictors for decision-making on a differential approach to choosing glucocorticosteroids (GCS) for children and adolescents with acute lymphoblastic leukemia (ALL). Subjects and methods. The analysis covered 1064 primary patients aged to 1 to 18 years with ALL who had been registered at the clinics of Russia and Belorussia in April 2002 to November 2006. Before induction therapy, the patients were randomized into a dexamethasone (DEXA) 6 mg/m2 group (n=539) and a methylprednisolone (MePRED) 60 mg/m2 one (n=525). Results. The entire group showed no statistically significant differences in survival rates between the patients receiving DEXA or MePRED. However, an analysis of age groups revealed the benefits of DEXA in children younger than 14 years (the event-free survival (EFS) was 76±2 and 71±2%, respectively (p=0.048); the overall survival (OS) was 81±2 and 77±2%, respectively (р=0.046); therapy-induced mortality was 6.4% (DEXA) and11.1% (MePRED) (р=0.014); the rate of isolated extramedullary relapses was 1.5% (DEXA) and 4.4% (MePRED) ( р=0.009). At the same time, EFS and OS in 14-to-18-year-old adolescents were statistically significantly higher than in those who used MePRED (EFS, 65±6 and 52±6%, respectively (р=0.087); OS, 72±6 and 61±6%, respectively; (р=0.17). Conclusion. The findings suggest that it is possible that the choice of a GCS for ALL therapy must be also based on a patient’s age. There is a need for further studies of this matter in prospective randomized multicenter trials in children and adolescents.

Aim. To evaluate the efficiency of the original ALL-MB-2002 protocol within the multicenter study of treatment of acute lymphoblastic leukemia (ALL) in children. Subjects and methods. A total of 1873 primary patients with ALL aged 1 to 18 years, of whom 1544 patients were enrolled in this study, were notified at 36 clinics of Russia and Belarus from April 15, 2002, to January 1, 2008. Results. With the median observation of 4.12 years, 7-year event-free survival (EFS) was 73±13%; overall survival (OS) 78±2%; relapse-free survival 82±1%. The rates of EFS and OS were equal and amounted to 76±2 and 80±2% in the standard-risk group (SRG) and intermediate-risk group (ImRG), respectively. In the high-risk group (HRG) patients, EFS and OS were as high as 30±6 and 37±6%, respectively. The frequency of relapses with central nervous system lesion was as much as 4.7% in all the patients, 6-year cumulative risk for isolated neurorecurrences being 2.5% in the SRG patients. Adolescents, patients with the baseline leukocytosis (more than 100109/l), and those with a splenic size of over 4 cm or more from the costal arch margin had substantially worse survival rates. A poor early response to therapy (on induction days 8 and 15) was also associated with its lower efficiency. Conclusion. Despite a considerable rise in the number of centers and a slight increase in the intensity of therapy, the results of the new ALL-MB-2002 protocol are as minimum equivalents obtained in the use of the previous ALL-MB-91 protocol. A significant improvement in the overall results of therapy and a reduction in the cumulative risk for isolated neurorecurrences were noted in the ImRG patients.

Aim. To analyze the specific features of recurrences of acute promyelocytic leukemia (APL) in children after standard therapy with daunorubicin, cytosine arabinoside (Ara-C), all-trans retinoic acid (ATRA) and to develop further programmed treatment policy. Subjects and methods. The study included 9 patients with recurrent APL. The recurrences developed significantly more frequently in a very high-risk group (patients with minimal residual disease being preserved after the intensive therapy phase). Induction used arsenic trioxide (ATO) and/or standard chemotherapy + ATRA; ATO monotherapy was in consolidation. CD34+ cells were mobilized until molecular remission was achieved with high-dose Ara-C and granulocyte colony-stimulating factor. Pretransplantation conditioning involved melfalan as a basic drug in combination with high-dose Ara-C (5 pts), treosulfan (1 pt) or bisulfan (1 pt). Six patients received gemtusumab ozogamicin, 3-9 mg/m2, at different stages of therapy. Results. Before therapy one patient died; 8 patients achieved the second molecular remission; CD34+ cell mobilization and sampling were effective in 7 cases. Five patients were in long-term molecular remission after autologous hemopoietic stem cell transplantation (autoHSCT). Follow-up was 23-40 months. One patient is being prepared for transplantation. Following autoHSCT, another patient with a developed repeat recurrence died from complications due to related partially compatible transplantation. Visceral, including cardiological, toxicity of therapy was insignificant. In the APL-2003 protocol, overall and event-free survival rates were 93±3 and 76±6%, respectively. Conclusion. The application of ATO and autoHSCT in recurrent APL makes it possible to achieve and preserve the second molecular remission in case of insignificant extrahematological toxicity. Russian clinics should have access to ATO.

Autoimmunity is a pathological process associated with a violation of immunological tolerance to normal structural components of the body (autoantigens), associated with the predominance of active (adaptive) immunity and manifested by hyperproduction of autoantibodies. Systemic autoimmune rheumatic diseases (SARDs) are among the most common and severe nosological forms of this pathology associated with autoimmunity. Problems of pharmacotherapy of SARDs are the subject of intensive research. At the beginning of the 21st century, more than 20 biologic agents were developed for the treatment of rheumatoid arthritis – monoclonal antibodies (mAbs) and recombinant proteins that control inflammation associated with the overproduction of “pro-inflammatory” cytokines, the use of which has dramatically improved the results of pharmacotherapy. However, much less research has been devoted to studying the possibilities of pharmacotherapy aimed at selective suppression of the “autoimmune” component of the pathogenesis of SADRs associated with uncontrolled activation of B cells and restoration of immunological tolerance to autoantigens. In the spectrum of drugs whose mechanism of action is associated with the suppression of pathological activation of B cells, the leading place is occupied by rituximab (RTM). It is noteworthy that 20 years ago (2004), a group of researchers led by prof. J.C. Edwards first demonstrated the effectiveness of RTM in patients with RA, which was soon successfully repositioned to treat a wide range of SARDs. A major achievement in the pharmacotherapy of SARDs is associated with the use of CAR (сhimeric antigen receptor) T cell therapy, developed for the treatment of refractory hematological tumors. The main component of CART-cells is a genetically engineered T-cell receptor that recognizes the target antigen without the participation of the major histocompatibility complex. Although limited, extremely impressive data regarding high remission rates have been obtained by adapting CD19 CART-cell therapy to treat patients with severe systemic lupus erythematosus (SLE) and other SARDs refractory to standard immunosuppressive medications. The article discusses the results of the use of CART-cell therapy in SLE and other SARDs and prospects for further research.

Duchenne muscular dystrophy is a genetic orphan neuromuscular disease caused by a mutation in the DMD gene encoding the protein dystrophin. As a result of developing and progressive muscle damage and atrophy, children lose the ability to walk, develop respiratory and cardiac disorders. The core elements of good care standards are early diagnosis, prevention and treatment of osteoporosis, daily physical therapy, regular rehabilitation, glucocorticosteroids, and control of heart and lung function. The clinical effect of new targeted pathogenetic therapies for Duchenne muscular dystrophy, restoring synthesis of full or truncated dystrophin, depend on their appropriate combination with existing standards of care.

New guidelines on diagnosis and treatment of a primary immune thrombocytopenia (ITP) in children and adults, on the basis of modern pathogenesis conceptions and considering possibilities of hematological practice in Russia are presented. Guidelines are based on a consensus of international and Russian experts on ITP. Diagnostic features of ITP are noted and various I, II and III lines treatment, including new effective medical products which have recently appeared in Russia, in particular, trombopoietin receptor agonists (romiplostim, eltrombopag), considerably expanded conservative treatment possibilities are offered. The presented guidelines can help hematologists to develop individual schedule for each given patients with ITP and to improve patients quality of life.

On the basis of health state analysis of children with long-term acute lymphoblastic leukemia (ALL) remission, rehabilitatiuon courses in children with the indicated pathology are followed in rehabilitation department of sanatorium. The sanatorium-resort stage of treatment promoted restoration of various organ and system failure at these children. Quality of life of children in study group were statistically significant higher than before sanatorium treatment as a result of complex rehabilitation. Results suggest that detailed examination of children with long-term ALL remission (5 years and more) is necessary for data obtaining about problems with physical, psychological and social failure and development of rehabilitation programs aimed to improvement of children health state in the future.

A graft versus host disease (GVHD) is one of the most serious complications occurring after allogeneic marrow cell transplantation. The investigation of the immune mechanisms responsible for the development of an acute GVHD has revealed a critical role of the regulatory T cells CD4+CD25+Foxp3+ that are responsible for the suppression of the function of effector rejection mechanisms, including the inhibition of the cytotoxic T lymphocytes CD8+, Т- helper cells CD4+CD25, natural killer cells and others that damage the host cells. Animal experiments have indicated the leading role of regulatory T cells in the initiation of GVHD. A number of human studies have analysed a correlation between the levels of the regulatory T cells CD4+CD25+Foxp3+ in the graft and/or blood of a recipient and the further occurrence of acute or chronic GVHD. The severity of an allogeneic GVHD is inversely related to the low expression of Foxp3.Besides regulatory T cells, mesenchymal stem cells (MSCs) have a significant immunosuppressive effect that has been demonstrated in the animal experiments and in the clinical trials in patients. MSCs do not only prevent the development of a GVHD, but may be used for the treatment of a just incipient process. In the opinion of a number of authors, MSCs prevent the development of a GVHD by directly affecting the induction of regulatory T cells in vivo.

Chronic immune thrombocytopenic purpura (ITP) is one of the most frequent immune hematological disorders in which development the leading part is played by the antibodies directed against a narrow spectrum of platelet antigens. Though death rate at chronic ITP is insignificant, no more than 1%; disease strongly reduces patients quality of a life, and frequently requires difficult and expensive treatment. Antiplatelets antibodies mediating ITP, are directed against glycoprotein GP IIb/IIIa and, less often, GP Ib/IX. At ITP can be registered both raised bone marrow platelet production and accelerated peripheral blood platelet clearance, and strongly decreased production and normal platelet life-span. Antibodies to platelet membrane glycoproteins directly disturb platelet production in bone marrow. Standard drug interventions at chronic ITP - glucocorticoids in various doses, high doses intravenous immunoglobulin, anti-D immunoglobulin, rituximab - rare lead to stable increase platelet number while in 2/3 patients splenectomy is effective. The new therapy approach in chronic ITP is stimulation of platelet production in bone marrow. Recombinant fusion protein Romiplostim stimulates trombopoietin receptor and it is effective at long-term therapy in 87% patients with chronic ITP irrespective of previous splenectomy. TPO antibodies development with romiplostim therapy was not revealed.

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants.

Cutaneous T-cell lymphomas are a heterogeneous group of T-cell lymphoproliferative diseases affecting the skin. Mycosis fungoides and Sezary syndrome are the most studied variants of them. The literature review includes the latest published data on the pathological processes development in mycosis fungoides and Sezary syndrome and the diagnosis of these diseases. The genomic instability features in cutaneous T-cell lymphomas are described, the existing hypotheses of the origin of these diseases are considered based on the results of T-cell receptor repertoire studying.

For the first time, the influence of COVID-19 on blood microrheology was studied. For this, the method of filtering erythrocytes through filters with pores of 3.5 μm was used. Filterability was shown to significantly decrease with the increasing severity of the patient’s condition, as well as with a decrease in the ratio of hemoglobin oxygen saturation to the oxygen fraction in the inhaled air (SpO2/FiO2). The filterability of ≤ 0.65, or its fast decrease during treatment, were indicators of a poor prognosis. Filterability increased significantly with an increase in erythrocyte count, hematocrit and blood concentrations of hemoglobin, albumin, and total protein. The effect of these parameters on the erythrocyte filterability is directly opposite to their effect on blood macrorheology, where they all increase blood viscosity, worsening the erythrocyte deformability. The erythrocyte filterability decreased with increasing oxygen supply rate, especially in patients on mechanical ventilation, apparently not due to the oxygen supplied, but to the deterioration of the patients’ condition. Filterability significantly correlates with the C-reactive protein, which indicates that inflammation affects the blood microrheology in the capillaries. Thus, the filterability of erythrocytes is a good tool for studying the severity of the patient’s condition and his prognosis in COVID-19.

Because of the successful implementation of modern treatment technologies at any stage of therapy of children with oncohematological diseases, their overall and disease-free survival has increased significantly. According to recent observations, 80 % of children after the completion of a special antitumor treatment continue to have changes of different organs. Almost all patients are at risk for late complications from the musculoskeletal system but little attention is paid to this issue. Evaluation of long-term complications from the musculoskeletal system and mineral metabolism in patients, development of their complex rehabilitation and prevention is an actual problem of pediatric oncology and hematology. This review summarizes data on long-term complications from the musculoskeletal system after special therapy. The necessity of diagnostics approaches harmonization and correction of not only the most common complications, but also little studied conditions, such as reduction of bone mineralization, is shown. It is noted that multidisciplinary rehabilitation treatment of children in remission can not only correct the consequences of the underlying disease, concomitant pathology and the consequences of special therapy but also reduce the disability of children.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by skin infiltration with malignant monoclonal T lymphocytes. More common in adults aged 55 to 60 years, the annual incidence is about 0.5 per 100 000 people. Mycosis fungoides, Sézary syndrome and CD30+ lymphoproliferative diseases are the main subtypes of CTCL. To date, CTCL have a complex concept of etiopathogenesis, diagnosis, therapy and prognosis. The article presented summary data on these issues.

Aim of publication. To present recent RGA evidencebased medicine centered guidelines on diagnosis, rational pharmacotherapy and management of irritable bowel syndrome (IBS). Summary. IBS - is a functional bowel disorder is manifested by recurrent abdominal pain that develops at least once per week and characterized by at least two of the following signs: it is related to bowel movements, associated to the change in stool frequency and/ or shape. These symptoms should be present in the patient for the last 3 months at overall duration of observation for six months or more. Similar to other functional gastrointestinal disorders, the diagnosis of IBS can be established at compliance of symptoms to Rome IV criteria and the absence of organic gastrointestinal diseases that could cause patient’s symptoms. Due to complexity of differential diagnostics, IBS should be considered as diagnosis by exclusion that require following investigations: clinical and biochemical blood tests; IgA or IgG anti-tissue transglutaminase antibodies; thyroid hormone levels; fecal occult blood test; glucose or lactulose hydrogen breath test for bacterial overgrowth syndrome; stool test for coliform bacteria, stool test for Clostridium difficile toxins A and B; fecal calprotectin level; abdominal ultrasound; upper and lower endoscopies, at indications - with biopsies. IBS treatment requires diet and lifestyle modifications, intake of pharmacological agents and psychotherapy. Antispasmodic medications (e.g.: hyoscine butylbromide, pinaverium bromide, mebeverine) are recommended for abdominal pain relief. For diarrhea-predominant IBS such medications as loperamide hydrochloride, dioctaedric smectite, non-absorbable antibiotic rifaximin and probiotics may be prescribed. For treatment of IBS with constipation use of bulking agents (psyllium), osmotic laxatives (macrogol 4000, lactulose), laxatives stimulating intestinal motility (bisacodyl) may be applied. Enterokinetic agent prucalopride may be prescribed at inefficacy of laxatives. Peripheral opioid agonists (trimebutine maleate) normalizing intestinal motor activity via action on different subtypes of peripheral opioid receptors, combined plant-derived medication STW 5 are applied as well. Conclusion. Implementation of clinical guidelines can determine timely diagnosis and treatment of various IBS types. The IBS is characterized by scalloping course with relapse periods that are provoked by psychoemotional stress and remissions. The risk of organic bowel diseases IBS patients is not higher, than in total population.

Secondary malignant diseases are dangerous long-term complications of allogeneic hematopoietic stem cell transplantation (HSCT). This article describes the group of secondary lymphoid neoplasms and presents a rare case of secondary Hodgkin disease in a 21-year patient 6 years after HSCT due to acute myeloid leukemia. This complication should be distinguished from the Hodgkin-like posttransplant lymphoproliferative disease, because of the different therapy approaches and outcomes. We describe their main features and differential diagnostic procedures.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective approach to cure numerous malignant and nonmalignant diseases. This method is more available now, respectively the number of survivors – recipients of HSCT increases every year. Among long-term complications of HSCT secondary solid cancers are one of the most life-threatening. We discuss different types of secondary solid tumours after HSCT and describe international recommendations of their screening and diagnostic. Several case reports from the single center could illustrate these serious late effects.

COVID-19 patients with acute respiratory distress syndrome (ARDS) have an immune imbalance when systemic inflammation and dysfunction of circulating T and B cells lead to a more severe disease. Using TREC/KREC analysis, we studied the level of mature naive T and B cells in peripheral blood of COVID-19 patients and its relationship with clinical and laboratory data. TREC/KREC analysis was performed by multiplex real-time quantitative PCR on a sample of 36 patients aged 45 years or younger. The reduced TREC/KREC level was observed in ARDS patients compared with non-ARDS patients, and similar results were found for the deceased patients. During days 6 to 20 of hospitalization, a higher neutrophil-to-lymphocyte ratio (NLR) was detected in ARDS patients compared with non-ARDS patients. TREC/KREC negatively correlated with NLR; the highest correlation was recorded for TREC per 100,000 cells with the coefficient of determination R2 = 0.527. Thus, TREC/KREC analysis is a potential prognostic marker for assessing the severity and outcome in COVID-19.

Background: Premature infants have a high risk of bacterial infections facilitated by the immaturity of their immune system.Objective: Our aim was to study the expression of Fc-gamma receptors of neutrophils and the possibility of its modulation in preterm infants (with a low, LBW, very low, VLBW and extremely low, ELBW, birth weight) with bacterial infection.Methods: We examined cord blood samples, as well as peripheral venous blood samples of newborns taken at 28–30th day of life. The flow cytofluorometry method was used to determine the level of surface expression of Fc-gamma receptors by neutrophils (CD64, CD32, CD16), phagocytic activity and oxygen burst of granulocytes stimulated with fluorescently labelled Escherichia coli. Results: We examined blood samples of 10 full-term infants, 20 preterm infants with LBW, 18 preterm infants with VLBW and ELBW. CD64 expression in preterm infants at birth was higher than in full-term children and made 6.0 (5.3; 9.8), 7.1 (5.1; 11.5), and 4.27 (2.4; 5.8) MFI respectively (p = 0.013). CD16 expression in preterm infants, in contrast, was lower: 99.7 (71.3; 126.0) and 80.9 (58.7; 114.8), and 125.3 (95.5; 144.1) MFI respectively (p = 0.021). By the end of the 1st month of life, CD16 expression of peripheral blood neutrophils in preterm infants increased to 126.6 (110.1; 129.0) MFI in children with LBW and to 118.5 (99.5; 132.2) MFI — in children with VLBW/ELBW. CD32 expression in compared groups did not differ. A correlation between the intensity of the oxygen burst of neutrophils and gestational age was established (r = 0.67; p

Abstract: current work is dedicated to analysis of features of clinical and encephalographic manifestations of focal epilepsy with secondary bilateral synchronization on EEG and onset in adolescence. The other aim was comparison these findings among patients with onset in adolescents and adult patients. We analyzed data of 66 adolescent patients and 61 adult patients with focal epilepsy with secondary bilateral synchronization on EEG. All patients were investigated with prolonged videoencephalographic monitoring and MRI of the brain. Analysis of types of epileptic seizures was made too. We revealed that etiological factor of focal epilepsy with secondary bilateral synchronization on EEG could not be found in case of onset of epilepsy in adolescence in contrast to epilepsy with onset in adult age. Secondary generalized convulsive seizures with fast generalization, bilateral myoclonic seizures and dialeptic seizures were more appropriate for focal epilepsy with secondary bilateral synchronization on EEG in case of onset of epilepsy in adolescence than for epilepsy with onset in adult age. Moreover focal epilepsy with secondary bilateral synchronization on EEG in case of onset in adolescence can form phonotypical copies of idiopathic generalized forms of epilepsy.

The article presents features of physiological processes and pathological conditions in under one-year children that predispose the development of iron-deficiency anemia. Basic methods of iron deficiency prophylaxis and principles of iron drug selection and dose selection for iron-deficiency anemia treatment for children in the stated age category are described in the article. Particular attention is paid to the prevention and treatment of iron deficiency anemia in preterm infants; foreign and domestic recommendations on this issue are presented. A practicing pediatrician needs to know the features of the disease’s development and treatment caused by differences in physical conditions accompanied by a high activity of metabolic processes and the immaturity of the young patients’ anatomic structures in order to identifiy and select the right iron-deficiency anemia treatment strategy.

Advances in the treatment of children with hematological and oncological diseases have led to accumulation of disabled children with severe organic and functional disorders that require the development of medical, neurocognitive, physical and psycho-social rehabilitation of these patients. On the basis of literature and own data about late effects and long-term results of treatment the concept of multidisciplinary rehabilitation, providing individual development, rehabilitation, education and social adaptation of sick children has been formulated.

The influence of previous antitumor therapy the efficacy and tolerability of high-dose chemotherapy with autologous hematopoietic progenitor cells transplantation (HCST) in 369 patients with Hodgkin, s lymphoma in the clinics of Russia and CIS countries was analyzed. Longterm treatment results of patients who have received 1 or 2 therapy lines before deciding about HCST were comparable (5‑year overall survival (OS) – 67 ± 3.8 % and 71 ± 5.0 %; freedom from treatment failure survival (FFTF) – 52.6 ± 3.9 % and 61 ± 5.0 %, respectively). The worst results (p < 0.05) are in patients who have received > 2 lines of therapy prior HSCT (5‑year OS – 46 ± 9.7 %, FFTF – 38.4 ± 9.0 %). The negative impact of previous treatment on the efficiency of hematopoietic material collection and hematopoiesis reconstitution as well observed in patients who received > 2 lines of therapy. Therefore, if the delay of HSCT in patients who achieved remission on secondline therapy was caused by organizational problems, for optimum results is necessary to conduct HSCT not later than second relapse while maintaining tumor chemosensitivity (third disease remission). However, when remission is not achieved after second-line therapy, is necessary to change the treatment regimen and performing HSCT only at confirmation of tumor chemosensitivity, because regardless of prior therapy line number, this approach leads to better results than earlier performing HSCT without remission.

Autologous hematopoietic stem cell transplantation (HSCT) is the standard treatment for patients with relapsed and primary refractoryHodgkin's lymphoma (HL). According to current recommendations HSCT must be performed in first relapse or after registration of primary resistance disease. However, the HSCT in optimal time for all patients with HL who need it is impossible, due to insufficient capacity of national transplant centers. Analysis of the HSCT results from 369 HL patients treated in Russia and other CIS countries clinics showed that intensive long-term standard chemotherapy prior to transplantation is a poor prognostic factor regarding to mobilization efficacy, hematopoiesis recovery and late HSCT results. In this regard, to achieve best results HSCT must be performed no later than the second relapse or immediately after registrationof primary resistance disease. Treatment results in patients received a lot of chemotherapy before transplantation is worse. But they stillhave a chance for a cure and should be considered as potential candidates to HSCT if obtained sufficient graft quality and hematopoietic response to induction chemotherapy is achieved.

Aim of this study was to investigate the incidence of malignant neoplasms (MN) in pediatric population (0–17 years) in the Chuvash Republic for the 15-year period (1994–2008). For study period total of 499 MN cases have been reported with an average of 33.3 ± 1.8 cases per year. The incidence rate of MN in children and adolescents was 10.1 ± 0.4 per 100.000. Distinct tendency to a change in the MN incidence rate has not been fo und, a regression analysis line is almost horizontal.

Key words: oncology, chemotherapy, radiotherapy, surgery, target therapy, clinical trials, history

Traditionally, the concern of fatal complication is a major obstacle to transfer patients with unfavorable course of Hodgkin’s lymphoma tonational transplantation centers. Early mortality after high-dose chemotherapy with autologous hematopoietic stem cell transplantation(HSCT) in the Russia, Ukraine and Belarus was assessed in this retrospective multicenter study.Patients and methods. The study included 372 patients with unfavorable course of Hodgkin’s lymphoma received HSCT between 01.1990and 06.2013: 35.5 % patients with primary resistance, 30.6 % with early relapse, 33.1 % with late relapse and 0.8 % during consolidation offirst complete remission.Results. During first 100 days after HSCT died 14 (3.8 %) patients, during first year – 31 (8.4 %) patients. During the study period a significant decrease in the 100-day and 1-year mortality rate was observed (p < 0.0001 for both). Among patients received HSCT in 1990–1995, 1996–2000, 2001–2005 and 2006–2013 the 100-day mortality was 19.4 %, 6.3 %, 1.1 % and 0.6 %, respectively. 1-year mortality for the same intervals was 32.3 %, 14.7 %, 4.5 % and 1.9 %, respectively.Conclusions. Currently HSCT in patients with unfavorable course of Hodgkin's lymphoma in national transplant centers, accompanied by an extremely low risk of fatal toxicity.

Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

This article provides an overview of clinical and biological features of most common malignant tumors in adolescents and young adults. The most effective pediatric and oncological treatment approaches to described diseases based on own experience are summarized.

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA) and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q) the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine) are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

Primary immune thrombocytopenia (ITP) is a rare (orphan) blood disease. Most frequent manifestations of ITP are purpura, petechiae and bleedings with many patients have either no symptoms or minimal bleedings manifestation. The management of ITP varies widely and must be based on current international recommendations and individual assessment of clinical course. The paper presents the results of interim analysis of clinical course and therapeutic approaches in the Russian register of ITP patients with immune thrombocytopenia and literature review about ITP treatment approaches.

This article provides an overview of research evolution of umbilical cord blood as a source of hematopoietic stem cells for transplantation. Phased developments of the technology of stem cells detection and selection, their proliferation, differentiation and function assessment using cultivation in vitro and in vivo in animal model was described. Differences of cord blood stem cells in comparison with those from other sources were described. The role of microenvironment for stem cells self-renewal and differentiation is shown. The possibility of stem cells biological properties modeling on example of using a vector based on HIV type 1 containing Notch genes, to regulate CD133+ and CD34+ cord blood stem cells proliferation is shown.

Unique experience of high-dose chemotherapy with consequent autologous hematopoietic stem cell transplantation in children with severe resistant multiple sclerosis (n=7) is shown in this article. At present time there is enough data on chemotherapy with consequent hematopoietic stem cell transplantation in children with severe resistant multiple sclerosis. This method was proved to be efficient and safe with immunoablative conditioning chemotherapy regimen. In patients included in this study the mean rate according to the Expanded Disability Status Scale was 5,94±0,2 (from 3 to 9) points. All the patients had disseminated demyelination loci, accumulating the contrast substance, in the brain and the spinal cord. After cyclophosphamide treatment in combination with anti-monocytes globulin the fast stabilization of the condition and prolonged (the observation period was 3-36 moths) clinical and radiologic as well as immunophenotypic remission with marked positive dynamics according to the Expanded Disability Status Scale were noted. No pronounced side-effects and infectious complications were mentioned. The maximal improvement according to the Expanded Disability Status Scale (EDSS) was 5,5 points, the mean — 2,7±0,1 (from 2 to 5,5) points accompanied with positive dynamics on the magneto-resonance imaging. The efficacy of the treatment was also proved by the positive changes in the lymphocytes subpopulation status in peripheral blood. The timely performed high-dose chemotherapy with consequent hematopoietic stem cell transplantation is an effective and safe method to slowdown the autoimmune inflammatory process. This method can be recommended to use in treatment of children with severe resistant multiple sclerosis.