High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a therapeutic option that allows potentiating the antitumor effect in patients with malignant neoplasms (MNs) belonging to the high-risk group. However, despite the effectiveness of this method, the risks of developing infectious and toxic complications in the early and late post-transplantation period are higher than the risks associated with treatment according to standard protocols and can significantly worsen the results of transplantation. We carried out a retrospective analysis of the results of auto-HSCT in a cohort of 156 patients with high-risk solid MNs treated at the L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation in 2020–2023. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology. The study included 78 (50%) boys and 78 (50%) girls, the median age of the patients was 8 years 7 months (9 months – 17 years 8 months). Auto-HSCT was performed in 90 (57.7%) patients with neuroblastoma, 25 (16.0%) – with Ewing's sarcoma, 16 (10.3%) – with germ cell tumors, 13 (8.4%) – with nephroblastoma, 7 (4.5%) – with retinoblastoma, 3 (1.9%) – with medulloblastoma, 1 (0.6%) patient with pleuropulmonary blastoma and 1 (0.6%) patient with sialoblastoma. We used the following conditioning regimens: treosulfan + melphalan ( n = 116), carboplatin + thiotepa + etoposide ( n = 17), melphalan ( n = 13), carboplatin + thiotepa + etoposide + cyclophosphamide ( n = 10). Depending on the clinical indications and the treatment protocol used, 136 (87.2%) patients underwent one course of HDCT, and 20 (12.8%) patients underwent tandem HDCT. In most patients, the median recovery time for granulocytes and platelets was 11 (8–19) days and 14 (12–21) days, respectively. The most common infectious complications in patients after auto-HSCT were mucositis (89.1%), neutropenic enterocolitis (76.9%), febrile neutropenia (71.2%), less often: catheter-associated bloodstream infection (9%), pneumonia (14.1%), acute respiratory distress syndrome (0.6%). As regards toxic complications, all patients had emetic syndrome, 98 (62.8%) had dermatological toxicity, 9 (5.8%) had hemorrhagic cystitis, 116 (74.3%) had hepatic toxicity, 14 (9%) had neurotoxicity, 102 (65.4%) had moderate nutritional insufficiency. Episodes of hemorrhagic syndrome due to thrombocytopenia were observed in 44.2% of patients. After auto-HSCT, most patients develop chemotherapy-induced (including infectious) complications, which can not only significantly disrupt the patients’ well-being and quality of life, but also, depending on the severity, pose a threat to their life. The correct choice of conditioning regimen, effective collection of hematopoietic stem cells, complex accompanying therapy, timely diagnosis and treatment of complications can significantly improve the results of auto-HSCT in children with high-risk solid MNs.

High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is used currently as a consolidating stage in cancer treatment protocols for children from different age groups with various malignant neoplasms. Auto-HSCT can improve both progression-free survival and overall survival of such patients. At the same time the optimization of the collection of autologous hematopoietic stem cells (HSCs) seems to be an important factor in the successful implementation of auto-HSCT. The purpose of this research was to evaluate the safety and effectiveness of the HSCs mobilization and collection method in children from different age groups with various malignancies. Materials and methods used: a single-center retrospective cohort study of 258 pediatric patients (median body weight 20.0 [13.8; 42.0] (7.0-95.0) kg and median height 116 [97; 155] (55.0-189) cm) with various cancers aged 1 to 18 y/o (median 78.0 [36; 144] (3-215) months old) who received treatment in Jan. 2020-Jan. 2023 at the Research Institute of Pediatric Oncology and Hematology named after Academician L.A. Durnov with the N.N. Blokhin Russian Cancer Research Center (Moscow, Russia). Patients were divided into 3 age groups: younger than 1 y/o, 1 to 10 y/o and 11 to 18 y/o. Results: 242 (93.8%) of HSC apheresis procedures were successful on the first attempt, 16 patients underwent repeated apheresis (a total of 274 procedures were performed). The median number of CD34+ cells obtained was 110.95 [45.6; 276.4] (0.70-2338.2) cells/µl, median apheresis duration was 253.5 [189; 338] (82-575) min. No serious complications were observed during the HSCs mobilization and collection in any patient. None of the patients developed hemodynamic disturbances. The main criteria for effectiveness was the CD34+/kg level, the median of which was 5.1 [2.4; 12.7] (0.01-95.6)•106. One of the safety criteria for the patients from all the three age groups was the absence of hemodynamic disorders and citrate reactions in the form of numbness, cyanosis of the skin and respiratory disorders. Another important safety criteria were the absence of a significant decrease in both platelet and hemoglobin levels. The median platelet levels prior to the procedure was 125.5 [68; 210] (14.0-815)•109/l and 129 [73; 210] (17.0-823)•109/l at the end of the procedure (p<0.001). Hemoglobin levels before and after the procedure were 100 [94; 110] (75-242) g/l and 99 [93; 109] (70-142) g/l, respectively (p<0.001). Considering it safe to reduce hemoglobin (g/l) and/or platelets (•109/l) by no more than 10 units in each measurement, in 87.6±4.1% (83.0-91.1) of observed cases the procedure was safe without statistically significant differences in all age groups. The effectiveness of the HSCs mobilization and collection method proposed by the Authors in children of the older age group (11 to 18 y/o) was the lowest and was statistically significantly different from the effectiveness in the group of children aged 1 to 10 y/o (p<0.001) with cancer and amounted to 84.5±4.4% (79.6-88.4). Conclusion: with the multidisciplinary team of practitioners, HSC apheresis in children is a safe and effective technique used as part of the complex cancer treatment in patients from poor prognosis groups. The apheresis algorithm that the Authors have proposed allows high-quality collection of CD34+ positive cells in amounts sufficient for further auto-HSCT.

Treatment of non-Hodgkin lymphomas (NHL) in children using risk-based chemotherapy protocols is currently effective in 80–95% of cases, even in advanced stages of the disease. However, relapsed/refractory forms of NHL (which are less common) have an extremely unfavorable course with low survival rates. The addition of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) to a comprehensive treatment program for relapsed/refractory forms of NHL can improve treatment results due to the antitumor effect of chemotherapy drugs of the conditioning regimen and the graft-versus-tumor effect, which is, however, less significant than in leukemia. Moreover, post-transplant complications after allogeneic HSCT in some cases can offset its positive results in NHL; therefore, to reduce toxicity, especially in severe somatic status of the patient, preference is often given to reduced-intensity conditioning regimens. This article presents two clinical cases. In one case, autologous HSCT was carried out for the first relapse of Burkitt's lymphoma. However, the patient developed a second relapse and underwent allogeneic HSCT from a haploidentical donor. In the second case, HSCT from an unrelated HLA identical donor was carried out in a patient with relapsed anaplastic large cell lymphoma. Both patients received reduced-intensity conditioning regimens. This approach helped to avoid the development of severe post-transplant complications, ensuring successful engraftment and achievement of donor hematopoietic chimerism. Early after transplantation, the patient with relapsed Burkitt's lymphoma developed a second tumor – acute T-lymphoblastic leukemia, from which the patient died. Despite treatment with targeted drug crizotinib, the second patient showed lymphoma progression, which resulted in death. The patients' parents gave consent to the use of their children's data, including photographs, for research purposes and in publications.

Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment option for relapsed / refractory (R / R) acute leukemia (AL) and high-risk AL. In this article, we present our own experience of allo-HSCT in children with R / R AL. The study was approved by the Independent Ethics Committee and the Scientific Council of the N. N. Blokhin National Medical Research Center of Oncology. Fifty-one patients with R / R AL were included in the study: 32 patients had acute lymphoblastic leukemia (ALL), 17 patients had acute myeloid leukemia (AML) and 2 patients had biphenotypic leukemia (BL). All patients underwent allo-HSCT from January 2021 to October 2022. The median age was 8.7 years (5 months – 17 years). At the time of allo-HSCT, 26 patients were in the second (and further) remission, the rest were in the first clinical and hematologic remission (high-risk AML and refractory ALL). Twenty-one (41.2 %) patients received allo-HSCT from a haploidentical donor, 19 (37.2 %) patients underwent allo-HSCT from an HLA-matched related donor and 11 (21.6 %) patients – from an HLA-matched unrelated donor. Pre-transplant conditioning in ALL: 27 patients received regimens based on total body irradiation at a dose of 12 Gy, 4 patients received busulfan-based conditioning regimens, and in 1 patient we used treosulfan. In AML and BL, we used conditioning regimens based on treosulfan/thiotepa (n = 10), treosulfan/melphalan (n = 8) or busulfan / melphalan (n = 1). Bone marrow (in 14 patients) and peripheral blood stem cells (in 37 patients) were used as a source of hematopoietic stem cells. In haploidentical allo-HSCTs in order to prevent graft-versus-host disease (GVHD) we performed TCRab/CD19 depletion followed by additional administration of abatacept / tocilizumab / rituximab on day –1 in 15 patients, 6 patients received post-transplant cyclophosphamide. In transplantations from HLA-matched related and unrelated donors, patients received combined immunosuppressive therapy with abatacept and rituximab on day –1, and calcineurin inhibitors were used as basic immunosuppressive therapy. All patients engrafted with a median time to engraftment of 13 (range, 9 to 24) days after allo-HSCT. Eight (15.7 %) patients developed a relapse of AL at different times after HSCT (five of them are alive). At the median follow-up of 9 (5–25) months, the overall and disease-free survival survival rates were 76.4 % and 68.8 %, respectively, for patients with AL. Acute GVHD was observed in 72.5 % of children, grade 3–4 GVHD was observed in 5.3 % of patients, and 13.7 % of children developed chronic GVHD. Most patients developed infectious complications in the early post-transplant period: febrile neutropenia (96.0 %), reactivation of viremia (47.3 %,) oropharyngeal mucositis (78.4 %), acute cystitis (12.3 %). The overall mortality rate was 17.6 %. Late mortality was associated with a relapse of AL.

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.

Alpha-mannosidosis is a rare autosomal recessive hereditary disease from the group of lysosomal storage diseases with diverse clinical manifestations, the most typical of which are neurodegenerative process, hearing loss, skeletal deformities and immunodeficiency. The only radical treatment for this disease currently is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Successfully performed allo-HSCT not only allows stoppage of the disease progression, but also leads to partial improvement in previously developed complications. The Article provides general information on the disease and demonstrates the Authors’ own experience of performing allo-HSCT in a patient with alpha-mannosidosis as well.

There is no doubt that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective treatments for many serious diseases. However, despite significant progress, allo-HSCT is still associated with a high rate of complications and mortality in the posttransplant period due to the toxicity of conditioning regimens, infectious and immune conditions. Acute complications such as endothelial injury, acute and chronic graft-versus-host disease (GVHD) remain the main causes of mortality after allo-HSCT. In our clinical case, we demonstrated an example of the development of such life-threatening complications as transplant-associated thrombotic microangiopathy and GVHD in a patient after repeated allo-HSCT, as well as the successful relief of these complications by modern therapeutic methods, including the introduction of closely related donor mesenchymal stem cells and the complement blocker eculizumab.

Despite improved understanding of the biology of the disease and the use of multicomponent chemotherapy, the prognosis for children with relapsed or refractory B-line acute lymphoblastic leukemia (B-ALL) remains poor. Currently, the only definitive treatment for these patients is allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can be performed after achieving immunohematological remission. Conducting highintensity polychemotherapy (PCT) blocks to achieve negative values of minimal residual disease (MRD) is often limited due to high toxicity. The developed monoclonal antibodies targeting cell surface antigens, such as CD19 and CD20, are actively used in children with relapsed/refractory B-ALL as part of “bridge therapy”, which allows achieving MRD-negative status without the use of intensive chemotherapy. However, new strategies are needed to improve the prognosis of these patients. The drug Inotuzumab ozogamicin has demonstrated efficacy in relapses of B-ALL and is actively used to achieve a negative MRD status before the allo-HSCT stage in children. In the presented article, in addition to a brief review of the literature, clinical experience with the use of this drug is demonstrated.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common treatment for a large number of pediatric diseases. Treatment planning is based on a careful selection of patients and donors, taking into account factors contributing to a successful outcome. The aim of our study was to analyze the results of 10 years’ experience in allo-HSCT gained at the Department of Bone Marrow Transplantation of the Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University. We retrospectively analyzed 506 patients who had undergone their first allo-HSCTs between January 2010 and December 2020. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation. We included 243 patients who had received allo-HSCT before December 2015 and 263 patients who had received allo-HSCT after January 2016. The gender distribution was 60.1% male (n = 304) and 39.9% female (n = 202). The median age was 7.13 years. Allo-HSCT recipients were divided into two groups: 236 children with non-malignant disease, 270 children with malignant disease. In the malignant group, 89 patients were in first complete remission (CR1), 92 were in second complete remission (CR2), and 20 were in third complete remission (CR3) and beyond; 63 patients had active disease (AD); 6 patients received no prior treatment. Two hundred and twenty patients underwent allo-HSCT from a fully matched family donor (MFD), 172 from a matched unrelated donor (MUD), 33 from a mismatched unrelated donor (MMUD) and 81 from a haploidentical (mismatched) family donor (MMFD). Two hundred and eighty-eight patients received bone marrow as a stem cell source, 208 received peripheral blood stem cells; 10 transplants were performed using umbilical cord blood stem cells. The 5-year overall survival (OS) in the entire cohort was 71.34 %. The 5-year OS in the patients who had undergone allo-HSCT between 2016 and 2020 was higher (p = 0.0014). After 2015, the rates of primary graft failure, the incidence of grade III–IV acute “graft-versus-host” disease (GVHD), and recurrence rates were significantly lower. No difference in the incidence of grade III–IV acute GVHD (p = 0.494) and OS rates (p = 0.138) was seen between different sources of hematopoietic stem cells in the patients who received an HLA-compatible transplant (MFD, MUD). Chronic GVHD was significantly dependent on the severity of acute GVHD and donor type. The 3-year OS rate for the patients in CR1, CR2, ≥ CR3, and AD was 84.4 %, 60.5 %, 56.8 %, and 46 % (p = 0.0034), respectively. The relapse rate of the patients in any remission was lower than of those in active disease (p = 0.015). The transplantation-related mortality in the first 100 days after allo-HSCT was 6.92% (n = 35). The patients who had undergone allo-HSCT after 2015 had lower rates of primary graft failure, a decreased incidence of severe GVHD, improved OS and relapse-free survival rates. The frequency of grade III–IV acute GVHD strongly correlated with HLA compatibility. Chronic GVHD was less frequent in MFD recipients. The risk of chronic GVHD increased with the severity of acute GVHD. The HLA mismatch between a donor and a recipient was associated with a decrease in OS. With each subsequent remission, the OS rate decreased. The risk of recurrence was higher in the patients transplanted in active disease. The results of this study can be used in clinical practice to plan therapy, choose an optimal donor, and develop strategies for the prevention and treatment of complications.

The article provides information about the features of the structure, development and differentiated approach to the appointment of dexapanthenol preparations used for the prevention and complex treatment of skin diseases in children of wounded age. Regular use of leave-on cosmetic products including body creams and lotions is very high among children aged 0–4 years. However, in most cases, recommendations for the use of topical baby skin care medicinal products and/or cosmetic products are based not on scientific evidence, but on common sense, expert opinions, advertising, personal preferences of parents, pharmacists, dermatologists and/or pediatricians. For example, adsorbing properties of baby powders are insufficient, and after absorbing moisture, they actually turn to “urine compresses” that aggravate the epidermis injury. After swelling, the starch-containing powders represent an excellent growth media for pathogenic and opportunistic microflora. It is noted that only proper skin care for young children allows you to preserve its integrity and functional state. Special attention is paid to the preparations of the Bepanten® series in the form of cream and ointment, which meet all the criteria for topical products, and can be used for the prevention and treatment of skin diseases in young children, effectively protecting the skin from irritants, promoting its healing and recovery, having an anti-inflammatory effect, increasing its elasticity, elasticity and are recommended for use as a means of basic care. Their effectiveness has been repeatedly confirmed in the numerous domestic and foreign randomized controlled studies in new-born populations at different gestational ages, which provided the scientific justification for their common use in the ‘real-life’ practice of pediatricians, dermatologists and allergists.

Relevance. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an integral part of the treatment of patients with high-risk malignancies. However, carrying out the mobilization and collection of hematopoietic stem cells (HSC) for patients weighing up to 15 kg is a complex task that requires a special approach and multidisciplinary interaction.The purpose of the study is to present the experience of collecting HSC in young children weighing up to 15 kg at the Research Institute of Pediatric Oncology and Hematology of the Federal State Budgetary Institution N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia.Materials and methods. The study included 30 patients weighing up to 15 kg who received treatment from January 2020 to May 2021 at the Research Institute of Pediatric Oncology and Hematology of the Federal State Budgetary Institution N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia. Median age was 30.6 (12–48) months, median body weight was 12.2 (7.8–15) kg. Apheresis in children weighing up to 15 kg was performed in the resuscitation and intensive care unit with the condition of pre-filling the cell separator circuit with a donor irradiated erythrocyte suspension to prevent hypovolemic complications. Thirty two apheresis was performed on a cell separator of the “Spectra Optia” type. To mobilize HSC, preparations of granulocyte colony-stimulating factor with the main active ingredient filgrastim were used.Results. Twenty eight HSC apheresis procedures were successful on the first attempt, 2 patients underwent repeated apheresis (a total of 32 procedures were performed). The median number of CD34+ cells obtained was 13.9 × 106/kg (0.04–92.0 × 106/kg), and the median apheresis duration was 251 (160–415) min. In 2 children during the procedure, an immediate organization of repeated venous access was required.Conclusions. Performing HSC apheresis in children weighing up to 15 kg and young children is a safe and effective technique with the participation of a multidisciplinary team. The apheresis algorithm proposed by us makes it possible to carry out a high-quality collection of CD34+ cells, sufficient for auto-HSCT.

One of the complications arising at the stage of hematopoietic stem cell transplantation (HSCT) is skin lesions. This complication is quite common and represents an important diagnostic and therapeutic problem. The main cause of skin lesions in HSCT is drug toxicity, but also infectious lesions. Each of the complications can manifest itself in varying degrees, as well as be combined with others, having a significant negative effect on the patient’s condition, in severe cases posing a threat to the patient’s life. This paper presents a clinical case of a patient with treosulfan toxicoderma who was treated with JELONET dressings.

Introduction. So far there has been no clear protocol on the treatment of bacterial infections in hematopoietic cancer patients undergoing polychemotherapy (PCT) and hematopoietic stem cell transplantation (HSCT). Guidelines available from antibiotic therapy panels such as EMBT, NCCN, ECIL, Sepsis-3 often fail to cover the entire spectrum of clinical risk factors of severe complications caused specifically by multiresistant Klebsiella pneumoniae.The aim of the study — is to showcase the clinical experience of demonstration of the experience of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin Russian Cancer Research Center with respect to adjusting antibacterial therapy for the spectrum of microorganisms found in the patient before the onset of antitumor therapy, and for the multiresistant microorganism findings in patients with blood cancers and febrile neutropenia (FN) undergoing PCT and HSCT.Materials and methods. The study involved five patients undergoing either PCT or HSCT for hematopoietic cancers at Research Institute of Pediatric Oncology and Hematology in October 2019 — October 2020, multiresistant Klebsiella pneumonia colonies found in each case. Results. Five patients with hematopoietic cancers and induced bone marrow aplasia were found to have multiresistant Klebsiella pneumoniae colonies on top of post-PCT/HSCT immunosuppression. Given high risk of death, these patients need early antibacterial therapy with reserve antibiotics outside standard empirical antibacterial treatment protocols should they develop FN. The Center's practices have shown that baseline protocols are often inadequate to the severity of these patients' conditions in a certain timeframe.Conclusions. To sum up the Center's limited experience, the finding is that additional research is required into the factors of risk of severe multiresistant Klebsiella pneumoniae infections in patients undergoing PCT and HSCT; algorithms must be developed for the treatment of patients in such a critical condition.

BCG (Bacillus Calmette–Guerin) vaccine is widely used for the vaccination of newborns within the first few days of life to prevent mycobacterial infections. However, complications occurring after BCG vaccination in patients with primary immunodeficiencies (PIDs) can lead to serious consequences for their health and life. BCG vaccine-related complications occurring in patients with severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD) after hematopoietic stem cell transplantation (HSCT) constitute an important problem. The article presents a retrospective observational analysis of 45 patients with SCID and CGD who received BCG vaccination and underwent HSCT. In the post-transplant period, 33 (73.3%) patients had BCG-related complications, either localized or generalized. The presence of BCG vaccine-related complications in the pre-transplant period was a significant predictor of the development of post-transplant complications. The most severe and long-term BCG vaccine-related complications were observed in the patients with SCID: the median time to the resolution of symptoms of BCG infection was 30 days and 100 days in the CGD patients and the SCID patients, respectively (p< 0.001). The severity of BCG vaccine-related complications, the nature of the primary disease and the presence of pre-transplant BCG vaccine-related complications did not affect the overall survival (OS) of the patients: OS for the entire study group was 79.5 ± 6.6%. Non-compliance with antimycobacterial prophylaxis prior to HSCT resulted in severe infections in a number of patients. The treatment of BCG vaccine-related complications included a combination of several antimycobacterial agents, and anti-inflammatory drugs (such as glucocorticoids, interleukin-1 and 6 receptor antagonists) in cases of immune reconstitution inflammatory syndrome (n= 18). The only effective method of prophylaxis of BCG-related infections in patients with SCID and CGD in the pre- and post-transplant period is the exemption of newborns from BCG vaccination based on their family history. Uninterrupted antimycobacterial prophylaxis in vaccinated patients in the pre- and post-transplant period is also important. Furthermore, an effective uniform strategy for the prevention and treatment of BCG vaccine-related complications in PID patients both before and after HSCT is needed.

Here we report the results of long-term monitoring of children with malignant infantile osteopetrosis (MIOP) before and after a successful hematopoietic stem cell transplantation (HSCT). We present patient health data collected 3-6 years after the completion of treatment, including information on the children's physical and mental health and social adaptation. The study was approved by the Independent Ethics Committee and the Scientifi Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation. HSCT is the only currently available radical treatment for MIOP. At the time of the treatment, all the patients exhibited severe visual impairment (descending optic atrophy), transfusiondependent bone marrow dysfunction, hepatosplenomegaly, signifiant skeletal abnormalities and growth retardation. In this study, we included 5 MIOP patients with successful transplantation who had been treated from 2014 to 2018. Four patients underwent HSCT from unrelated 10/10 HLA-identical donors and 1 patient received HSCT from a related 10/10 HLA-identical donor. The ratio of boys to girls was 2:3, the median age at the time of the transplantation was 7 (2–11) years. All the patients demonstrated full donor chimerism after HSCT. Hematopoietic recovery was achieved within the fist 150 days after HSCT. Radiological investigations showed gradual partial reduction of skeletal changes typical of MIOP. All the subjects demonstrated growth of the axial skeleton, facial bone remodeling and abatement of phenotypic features of the disease. The patients' vision remained the same as before HSCT. All the patients reported that their health and quality of life had improved after HSCT. The degree of visual impairment had a substantial impact on the quality of life and social rehabilitation of the patients. The second major factor affcting the quality of life was the development of chronic conditions after HSCT, namely, epilepsy and chronic “graft-versus-host” disease of the lung that require constant medical monitoring and limit rehabilitation potential. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications.

Umbilical cord blood (CB) has been used successfully as hematopoietic stem cells (HSCs) in adults and adults with malignant and non-malignant diseases in which there are indications for HSC transplantation (HSCT), and when an HLA-compatible related or unrelated donor is not available. CB, like any source of HSC, has certain advantages and disadvantages, which also determine the features of its use in transplantation. The article presents the experience of using CB as a source of HSC in pediatric patients at the Russian Children's Clinical Hospital (RCCH). Materials and methods of research: in a retrospective single-center continuous non-randomized uncontrolled open study includes 16 patients with various malignant diseases and 16 patients with non-malignant diseases, who underwent CB transplantation in the bone marrow transplantation department of the Russian Children's Clinical Hospital from 1997 to 2012. The peak of CB transplant activity occurred in the period from 2006 to 2010. The age of the patients at the time of the transplantation ranged from 6 months to 14 years. In 10 patients, a CB transplant from HLA-identical related donors was used, in 22 – from unrelated HLA-identical and HLA-incompatible for 2 or more antigens obtained from domestic CB banks. In addition to CB, six children were given bone marrow or peripheral blood stem cells from HLA-identical siblings as a transplant. The majority of patients (n=20) received one CB sample, 10 patients – 2 samples and two – 3. Results: implantation of the transplant was recorded in 27 children (84%), which 17 (53%) were alive, 10 (31%) died at different timesof post-transplant period. In 5 (16%) patients, implantation did not occur, of which one (3%) died, the cause of mortality in pediatric patients was a relapse of the underlying diseases. Acute graftversus-host reaction (GVHD) after CB transplantation was assessed in 27 (84%) patients of this study, among them 17 (63%) were diagnosed with acute GVHD stages I-II, 3 (11%) – stage III–IV (life-threatening form). Chronic GVHD was assessed in 18 (56%) patients included in the study, with 5 (28%) diagnosed with a limited form and 3 (17%) with an extensive form. Overall survival (OS) for the entire group of patients (n=32) was 58,3±8,8%, 5-year dormant survival rate (DSR) – 53±8.8%. OS in non-malignant diseases was higher (68%) than for malignant diseases (56%), but no statistically significant differences in OS were obtained in the two groups (p>0,05), as well as when comparing OS and DSR when using one or several samples of CB. Conclusion: CB remains available and acceptable source of stem cells for HSCT. At our center, the survival rates of patients after CB transplantation are comparable to those of international registries. The improvement of the method and the results of haploidentical SCT in recent years has led to a decrease in interest and transplantation activity (including in our center) using CB as a source of HSC. However, the unexplored antileukemic potential of CB stem cells, as well as a number of potential resources for improving and optimizing the use of this HSC source, may increase the chances of future CB transplantation.

Here we report the results of long-term monitoring of children with malignant infantile osteopetrosis (MIOP) before and after a successful hematopoietic stem cell transplantation (HSCT). We present patient health data collected 3-6 years after the completion of treatment, including information on the children's physical and mental health and social adaptation. The study was approved by the Independent Ethics Committee and the Scientifi Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation. HSCT is the only currently available radical treatment for MIOP. At the time of the treatment, all the patients exhibited severe visual impairment (descending optic atrophy), transfusiondependent bone marrow dysfunction, hepatosplenomegaly, signifiant skeletal abnormalities and growth retardation. In this study, we included 5 MIOP patients with successful transplantation who had been treated from 2014 to 2018. Four patients underwent HSCT from unrelated 10/10 HLA-identical donors and 1 patient received HSCT from a related 10/10 HLA-identical donor. The ratio of boys to girls was 2:3, the median age at the time of the transplantation was 7 (2–11) years. All the patients demonstrated full donor chimerism after HSCT. Hematopoietic recovery was achieved within the fist 150 days after HSCT. Radiological investigations showed gradual partial reduction of skeletal changes typical of MIOP. All the subjects demonstrated growth of the axial skeleton, facial bone remodeling and abatement of phenotypic features of the disease. The patients' vision remained the same as before HSCT. All the patients reported that their health and quality of life had improved after HSCT. The degree of visual impairment had a substantial impact on the quality of life and social rehabilitation of the patients. The second major factor affcting the quality of life was the development of chronic conditions after HSCT, namely, epilepsy and chronic “graft-versus-host” disease of the lung that require constant medical monitoring and limit rehabilitation potential. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications.

Relevance. Infectious septic complications caused by polyresistant gram-negative micro-organisms are a pressing issue in the treatment of patients after polychemotherapy (PCT) and hematopoietic stem cell transplantation at the high risk of the fulminant current and high lethality against the background of hematopoesis aplasia. One of the therapeutic strategies of antimicrobial treatment is the systematic use of 0.5 % hydroxymethylquinoxaline dioxide (dioxidine) solution in the complex antibacterial therapy of patients with severe infectious-septic complications. The preparation has a bactericidal type of action, a wide spectrum of antibacterial activity. Experience in adult clinical practice has demonstrated the effectiveness of dioxidine in the treatment of the most severe forms of aerobic and anaerobic infection. Strict dose enforcement and injection technique to avoid the appearance of side effects. Data on the intravenous use of dioxin in children are presented in a limited number of scientific literature.The aim of the study was to demonstrate the efficacy of systemic use of hydroxymethylquinoxaline dioxide (0.5 % dioxidine solution) in children with infectious complications progressing against the background of aplasia of hematopoiesis caused by multidrug-resistant pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia.Materials and methods. 16 patients with a verified gram-negative infection were prescribed 0.5 % hydroxymethylquinoxaline dioxide solution as part of a combination antimicrobial therapy were included in the retrospective study. The median age of patients was 5 years (6 months – 16 years), 11 (69 %) were boys and 5 (31 %) girls.All children included in the study has infectious-septic complications at the PCT-induced hematopoietic aplasia, obtained according to the protocols of the main disease: severe combined immune deficiency (n = 2), idiopathic aplastic anaemia (n = 3), solid tumor (n = 2), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2). The main criterion for adding to the study was the existence at the least one site with a verified gram-negative infection (Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia): bacteriemia (n = 11), oral mucosa (n = 6), ulcerative necrotic damage of perineum (n = 6), enterocolite (n = 6), infectionseptic compartments in the subcutaneous fat (n = 4), pleuropneumonia (n = 4), abscesses and inflammatory infiltration of the liver, spleen, pancreas, kidneys, lymph nodes (n = 1), infection of soft tissues in the area of the ventricular bypass with inflammatory changes of the brain membranes (n = 1).All patients received 0.5 % of the solution of dioxin by injection according of vital importance, as they had pathogens with confirmed laboratory resistance or clinical progression of the infectious process against the background of combined antibacterial therapy.Discussion. There is a complete control of fulminant developing infectious-septic processes caused by polyresistant micro-organisms against the background of hydroxymethylquinoxaline dioxide therapy in all 16 patients. The eradication of the pathogen, according to the microbiological study, has been confirmed in almost all observed patients, the efficacy of the drug has been preserved throughout the period of treatment, and the resistance of micro-organisms has not been observed. Strict adherence to the dosing and infusion technique of hydroxymethylquinoxaline dioxide has helped to achieve the full resolution of the infection process in all children without side-effects.Conclusion. On the basis of the experience presented, in immunocomputed patients of young age, 0.5 % dioxidine solution can be used as a necessary reserve preparation for the treatment of the most severe forms of infections of different localization, caused by polyresistant strains of gram-negative micro-organisms.

BCG (Bacillus Calmette–Guérin) vaccine is widely used for the vaccination of newborns within the first few days of life to prevent mycobacterial infections. However, complications occurring after BCG vaccination in patients with primary immunodeficiencies (PIDs) can lead to serious consequences for their health and life. BCG vaccine-related complications occurring in patients with severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD) after hematopoietic stem cell transplantation (HSCT) constitute an important problem. The article presents a retrospective observational analysis of 45 patients with SCID and CGD who received BCG vaccination and underwent HSCT. In the post-transplant period, 33 (73.3%) patients had BCG-related complications, either localized or generalized. The presence of BCG vaccine-related complications in the pre-transplant period was a significant predictor of the development of post-transplant complications. The most severe and long-term BCG vaccine-related complications were observed in the patients with SCID: the median time to the resolution of symptoms of BCG infection was 30 days and 100 days in the CGD patients and the SCID patients, respectively (p< 0.001). The severity of BCG vaccine-related complications, the nature of the primary disease and the presence of pre-transplant BCG vaccine-related complications did not affect the overall survival (OS) of the patients: OS for the entire study group was 79.5 ± 6.6%. Non-compliance with antimycobacterial prophylaxis prior to HSCT resulted in severe infections in a number of patients. The treatment of BCG vaccine-related complications included a combination of several antimycobacterial agents, and anti-inflammatory drugs (such as glucocorticoids, interleukin-1 and 6 receptor antagonists) in cases of immune reconstitution inflammatory syndrome (n= 18). The only effective method of prophylaxis of BCG-related infections in patients with SCID and CGD in the pre- and post-transplant period is the exemption of newborns from BCG vaccination based on their family history. Uninterrupted antimycobacterial prophylaxis in vaccinated patients in the pre- and post-transplant period is also important. Furthermore, an effective uniform strategy for the prevention and treatment of BCG vaccine-related complications in PID patients both before and after HSCT is needed.

CAR-Т cell therapy with the use of cytotoxic lymphocytes with chimeric antigen receptors occupies an important place among modern approaches to the cancer treatment. This therapy has established itself as an effective method of the treatment of CD19+ acute lymphoblastic leukemia. Nevertheless, the recurrences of the illness are not uncommon; the treatment of solid tumors with genetically engineered lymphocytes shows modest results and it is accompanied by the high toxicity. One thing, however, is certain: CAR-Т cell therapy has great potential in the treatment of cancer and further improving of the structure and functions of genetically engineered lymphocytes with chimeric Т cell receptors help greatly increase the efficiency of antitumor treatment.The review includes the current data on the structure of chimeric lymphocytes of different generations and the trends in improving CAR-Т cell therapy. It includes also the fundamental platform for formation of ideology of use CAR-Т cells for the treatment of solid malignant tumors.