Background. In the literature, information on the overexpression of disialoganglioside GD2 on the cells of malignant neoplasms is not uncommon. In this regard, this marker should be considered as a tumor-associated antigen, which may be a target on the cell surface in patients with poor prognosis.

The aim of the study – improve the efficacy of the treatment of children and adolescents with refractory and recurrent solid malignancies (soft tissue, undifferentiated (unSA) and bone sarcomas) by incorporating targeted immunotherapeutic options (immunotherapy with antiGD2 monoclonal antibodies (MA)) into comprehensive therapy programs.

Materials and methods. Ten patients with GD2-positive relapsed/refractory soft tissue sarcomas (STS, n = 4), osteosarcomas (OS, n = 2), Ewingʼs sarcomas (ES, n = 4) and unSA (n = 1) were included in the study. The gender ratio was 2.3:1 (boys:girls). The mean age at the time of inclusion in the study was 12 ± 2 years. The most of all patients (80 %) had a status of “primary resistant disease”. GD2  quantitative expression level was 29 ± 11 % (0.9 to 85 %). Patients were represented by deeply pretreated patients who received 8 to 25 cycles of 2+ line chemotherapy (mean 13). A total of 7 patients completed the full reinduction treatment (6 cycles of chemoimmunotherapy). All patients received anti-GD2 MA 100 mg/m2 as an intravenous 5-day infusion every 4 weeks, and treatment was continued until disease progression or 6 cycles. Fifty-two cycles of immunotherapy were performed.

Results. Pain syndrome was the most frequently diagnosed (after 16 cycles, or in 30.7 % of cases); 5 (9.6 %) cycles each were accompanied by diarrhea, cytokine release syndrome, and increased capillary permeability syndrome. The immediate results varied according to the histological subtype of the tumor. The overall objective response rate was 43 % (3/7): 2 patients achieved complete remission (CR) and one achieved partial remission (PR). The disease control rate (CR + PR + stable) was 86 % (6/7). The clinical response rate 6 months after completion of chemoimmunotherapy ranged from 0 % (2/2) in ES to 50 % (1/2) in OS. In 43 % (3/7) of evaluable patients, disease progression was diagnosed after a mean of 5 months. At follow-up after 12 and 24 months, CR persisted in all patients with STS (100 %). Progression-free survival (PFS) in patients with STS at 6, 12 and 24 months was 100 % (PFS6, PFS12, PFS24, respectively). PFS6 in OS and ES patients was 100 % and 50 %, respectively, gradually decreasing to 0 %. The study revealed a very strong positive straight-line positive functional correlation between quantitative GD2 expression and progression-free survival (r = 0.971, p = 0.00006).

Conclusion. Passive immunotherapy with monoclonal antibodies is a safe treatment method without severe immune-related adverse reactions. Patient follow-up and evaluation of the efficacy and safety of the drug after the end of the therapy plan continues until today, which allows a more detailed and objective evaluation of the results of immunotherapy according to the purpose of the study.

Introduction. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective method of treatment a number of malignant neoplasms and severe non-malignant diseases in addition to standard treatment protocols. Auto-HSCT requires previous successful collection of autologous hematopoietic stem cells (HSC) by apheresis with preliminary mobilization. Standard mobilization schemes include the use of granulocyte colony-stimulating factor (G-CSF), however, some patients have insufficient mobilization (IM) of HSC, which creates significant obstacles to the collection of HSC. Timely detection of predictors of IM can allow to adjust its protocol, as well as individualize the HSC apheresis regimen. Aim of the study – based on the results of the analysis of mobilization and apheresis modes of autologous HSC in patients with various malignant neoplasms to identify the most significant factors causing IM of HSC for the further development of methods for optimizing the mobilization and collection modes of HSC.

Materials and methods. The study included 257 patients aged from 3 to 215 months (median age – 84 [36.0; 144.0] months) with various malignant neoplasms who received treatment at the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia from 2019 to 2023. According to the treatment protocol of malignant neoplasms, all patients received high-dose polychemotherapy followed by auto-HSCT as a consolidation phase of treatment. HSC mobilization was performed in advance in order to successfully perform apheresis of autologous HSCs. The main group (the group IM, n = 64) of patients included persons who did not achieve a CD34⁺ cells in peripheral blood of 20 cells/μl by the day of apheresis, despite full compliance with the established mobilization protocol. The comparison group (the “sufficient mobilization” (SM) group, n = 193) consisted of patients who achieved a CD34⁺ cells in peripheral blood of 20 cells/μl or more by the day of apheresis. Mobilization regimens included various chemotherapeutic agents (G-CSF, cyclophosphamide in the previous chemotherapy scheme, plerixafor and its combinations), the dose of which, the duration of the regimen, as well as the dose escalation depended on the initial characteristics of both the main treatment protocol and the somatic and infectious status of the patient. In the studied patient groups, the frequency of factors potentially capable of influencing the quality of mobilization before HSC apheresis was analyzed: the tumor type and stage, the number of previous courses of polychemotherapy, the presence and amount of myelotoxic agents in polychemotherapy, recovery of hematopoiesis before the start of mobilization, pretreatment, response to therapy, history of radiation therapy and surgery, the need for escalation of the G-CSF dose in the mobilization mode.

Results. Significant differences (p < 0.05) between the comparison groups were obtained for such factors influencing the success of mobilization as the main diagnosis (the worst mobilization results were in patients with Ewingʼs sarcoma), tumor stage and response to previous treatment (mobilization was more successful in patients with disease stabilization). A significant negative impact on the efficiency of mobilization was also demonstrated by such factors as the lack of hematopoiesis recovery before mobilization, pretreatment (4 or more courses of chemotherapy preceding mobilization), the presence of radiation therapy, a combination of radiation and surgical treatment in the therapy protocol preceding mobilization, the presence of carboplatin and temozolomide in the chemotherapy course, as well as three myelotoxic agents simultaneously, and escalation of the G-CSF dose during mobilization. Despite the worse characteristics of the graft, as well as the technically more difficult procedure for collecting HSCs in the IM group of patients, the average number of CD34⁺ cells per kg was 1.5 × 10⁶ /kg [0.7–2.7], which demonstrates the possibility of achieving a suboptimal number of stem cells in one apheresis procedure even in patients with poor mobilization. However, in the group of IM, not only escalation of doses of stimulant agents, but also prolongation of the apheresis procedure itself with an increase a number of processed blood volume and the volume of the graft. This not only increases the resources spent on the procedure, but also increases the risks for patients and creates additional difficulties for specialists performing the procedure. To optimize the mobilization and collection modes of the HSC, it is necessary to take into account the presence of risk factors for poor mobilization and plan in advance for such patients an individual regimen of both escalation and monitoring of the mobilization, as well as preparation for a special regimen of HSC collection.

Conclusion. According to the results of our study, significant predictors of IM are the characteristics of the main diagnosis, not an achievement of tumor regress, lack of hematopoiesis recovery before the start of mobilization, pretreatment, the presence of radiation therapy in the treatment protocol preceding mobilization, a combination of radiation and surgical treatment, the presence of carboplatin and temozolomide in the chemotherapy scheme, as well as three myelotoxic agents simultaneously, and escalation of the G-CSF dose in the mobilization mode. It is the patients who may require optimization of the mobilization and collection of HSCs.

Introduction. The prognosis for patients with relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains extremely unfavorable, with long-term overall survival (OS) rates less than 10 %. One of the major acquired mechanisms of immunological resistance is loss heterozygosity of HLA (LoH) genes located on chromosome 6. For patients who have developed HLA LoH relapse, immunotherapy based on independent antigen recognition pathways such as blinatumomab therapy, CAR-T therapy or second allo-HSCT is being considered.

The aim of the study – to analyze the efficacy of immunotherapy options in children with HLA LoH relapse based on donor lymphocyte infusions (DLI), blinatumomab and second allo-HSCT.

Materials and methods. We have analyzed 26 patients with HLA LoH confirmed relapse with bone marrow involvement after allo-HSCT. Acute myeloid leukemia was detected in 6 (23 %) patients, acute lymphoblastic leukemia (ALL) in 20 (77 %) patients (B-ALL in 16 patients, T-ALL in 4 patients). Most patients were observed after allo-HSCT from a haploidentical donor, in 24 (92 %) patients and 2 (7.6 %) patients developed relapse after allo-HSCT from a full matched related donor. Isolated medullary relapse was diagnosed in 20 patients; combined relapse was noted in 6 patients (with CNS involvement in 5 patients, testicular relapse in 1 patient).

Results. In the bispecific T-cell activator immunotherapy group, 5 patients with ALL received blinatumomab. Blinatumomab in combination with DLI was given to 3 patients. A response to therapy by the clinical and hematological remission was observed in all patients. MRD negative status was achieved in 4 patients. Subsequently, 2 patients developed medullary relapse and died of the disease progression; 1 patient died of neurotoxic complications after second allo-HSCT; 2 patients are alive in remission after the second allo-HSCT, with follow-up of 10 and 4 months. Second allo-HSCT was performed in 8 patients, with donor change in 7 patients. In the comparable analysis of the efficacy of HLA LoH relapse therapy, the 2-year OS in the second allo-HSCT group was 71.4 %, compared to 26.3 % in patients who did not undergo second allo-HSCT with donor change (p = 0.06). Comparing the OS results of patients with second allo-HSCT (n = 7), DLI (n = 8) and other therapy (n = 11), the favorable effect was seen by the second allo-HSCT group, where the OS was 71.4 %, 25 % and 27.3 % respectively (p = 0.045).

Conclusion. The presented analysis of the efficacy of different therapeutic options for HLA LoH relapse shows a significant benefit of the second allo-HSCT in this cohort. The investigation of loss of HLA (LoH) heterozygosity in relapse after allo-HSCT in routine practice may differentiate approaches to relapse therapy and decrease the time frame for the second allo-HSCT.

Background. Despite scientific advances in recent decades, childhood cancer still has significant disparities in survival, partly due to late detection and misdiagnosis.

The aim of this study was to determine the level of knowledge and barriers to early cancer diagnosis based on a survey of pediatricians in Russia.

Materials and methods. A cross-sectional online survey was developed using a structured questionnaire containing the following sections: demographic data, knowledge about childhood cancer, and perceived barriers to early diagnosis of childhood cancer. The questionnaire was designed for pediatricians providing primary care.

Results. A total of 597 responses were received: 236 (39.5 %) did not receive training in pediatric oncology in medical school, 489 (81.9 %) had never received training in pediatric oncology as part of postgraduate education or continuing medical education. A total of 216 (36.2 %) pediatricians had no training in pediatric oncology. Half (54.7 %) had never encountered primary cancer patients in their practice. Less than 50 % of the survey participants scored correctly on childhood cancer. The three most common barriers, according to pediatricians, were parents’ late presentation to medical care, the absence of pediatric oncologists in primary care facilities, and the lack of direct access to necessary diagnostic tests at the pediatrician level.

Conclusion. This study demonstrated the limited training of pediatricians in pediatric oncology. It revealed their low awareness of childhood cancer. These results indicate an urgent need for targeted interventions to address the identified barriers to early cancer diagnosis in Russia. It is necessary to strengthen the healthcare system and medical education to accurately diagnose and effectively treat all children with cancer.

Introduction. The prognosis in patients with Ewingʼs sarcoma (ES) is determined by a combination of factors such as the size of the primary tumor, the location and extent of the process, as well as the clinical response to drug treatment. Taking into account all prognostic indicators and the possibility of their correct assessment are necessary to stratify the risk of progression before starting treatment and to select the optimal approach to therapy. We have developed a mathematical prognostic model that allows us to form risk groups before starting program therapy.

Materials and methods. A retrospective cohort single-center study was conducted in children with ES, who received treatment from 2012 to 2023 of the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. To determine significant independent prognostic factors, univariate and multivariate Cox regression analysis was used. Prognostic significance was assessed by constructing ROC curves.

Results. The following previously unassessed independent risk factors for progression were identified: initially high lactate dehydrogenase levels, leukocytosis, hyperfibrinogenemia and treatment program. A mathematical prognostic model for calculating the individual risk of progression has been created. The sensitivity of the developed system was 87.7 %, specificity – 94.0 %, accuracy – 91.3 %, positive predictive value – 91.9%, negative – 90.9 %.

Conclusions. The developed Individual Probability of Progression Index demonstrated high prognostic ability in children with ES.

Background. The gastrointestinal form (GI) is a common variant of acute graft-versus-host disease (aGVHD) in children who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). In Russia, there are no large studies devoted to studying the characteristics of the endoscopic picture and tactics of endoscopic diagnosis of patients with GI aGVHD.

Purpose of the study – to develop an optimal algorithm for conducting endoscopic examination in children with cancer who have undergone allo-HSCT, to compare data on the macroscopic picture of detected changes in the gastrointestinal mucosa in accordance with the Cruzz-Correa classification and the Freiburg criteria, to determine the sensitivity, specificity and diagnostic accuracy of endoscopic examination in conducting a differential diagnosis between GI aGVHD and nonspecific/viral lesions of the gastrointestinal tract, as well as assessing the advantages of a comprehensive endoscopic examination in the diagnosis of GI aGVHD.

Materials and methods. In a retrospective study conducted at the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia in the period from January 2021 to September 2023, data from 100 (100 %) patients diagnosed with acute leukemia, under the age of 18 years, who underwent allogeneic HSCT were analyzed. The main study group consisted of patients with suspected GI aGVHD (n = 27; 27 %), who underwent a complex endoscopic examination – esophagogastroduodenoscopy (EGDS) and colonoscopy. When diarrhea syndrome and/or other manifestations of gastrointestinal disorders appeared after allogeneic HSCT in 60 (60 %) patients, to exclude bacterial, viral infections, fungal infections and toxic effects of drug therapy, patients at the first stage underwent microbiological examination of stool and rectal swab. At the second stage, after excluding the above-described factors and suspicion of the development of GI aGVHD, patients (n = 27; 27 %) underwent a comprehensive endoscopic examination, accompanied by the collection of biopsy material from all altered areas of the gastrointestinal mucosa, as well as unchanged areas of the duodenum and rectum. Intestines for histological examination to exclude GVHD and virological studies to exclude acute intestinal infections (Astrovirus, Norovirus genotype 2, Adenovirus F, Rotavirus A), cytomegalovirus infection (CMV), human herpes virus type 6 (HHV-6) and Epstein–Barr Virus (EBV) in the intestinal wall using Polymerase chain reaction (PCR). The results of a comprehensive endoscopic examination were compared with data from laboratory diagnostic methods.

Results. According to the results of complex morphological, immunohistochemical, microbiological, virological studies of biopsy samples of the gastrointestinal mucosa, as well as PCR methods for diagnosing stool and rectal smear, GI aGVHD was confirmed in 22 (81.5 %) of cases (n = 22), of which in 13.6 % of cases (n = 3) there were no visual changes in the mucous membrane. In 5 (18.5 %) patients from the group of patients with suspected GI aGVHD, a diagnosis of viral enterocolitis was established in 14.8 % of cases (n = 4): 1 (3.7 %) patient – adenoviral, 2 (7.4 %) – cytomegalovirus and in 1 (3.7 %) patient – neutropenic enterocolitis; and in 1 (3.7 %) patient – nonspecific changes in the mucous membrane caused by the use of high-dose polychemotherapy. The diagnostic value of forceps biopsy in the diagnosis of GI aGVHD from altered areas of the mucous membrane was 86.4 % (n = 19), from unchanged areas of the duodenum. – 9.1 % (n = 2) and rectum – 4.5 % (n = 1). Significantly more often (p < 0.05) changes in the mucous membrane were detected in the colon (n = 11; 50 %) and duodenum (n = 5; 22.7 %), less often in the stomach (n = 2; 9.1 %) and esophagus (n = 1; 4.5 %) in the form of hyperemia, pastiness (n = 13; 59.1 %) and multiple erosions (n = 5; 22.7 %). Specific changes in the mucous membrane (n = 6; 27.3 %) were determined in the form of multiple erosions merging with each other, occupying most of the surface of the duodenum and colon (n = 5; 22.7 %), and complete detachment of the mucous membrane 12 – duodenum (n = 1; 4.5 %). According to the Cruz-Correa classification, in 9.1 % of cases (n = 2) grade 0 was established, in 9.1 % (n = 2) – I, in 13.6 % (n = 3) – II, in 9.1 % of observations (n = 2) – III and in 4.5 % of observations (n = 1) – IV degree of GI aGVHD of the upper gastrointestinal tract. According to the Freiburg criteria – I degree GI aGVHD of the lower gastrointestinal tract in 4.5 % of cases (n = 1), II – in 36.4 % (n = 8), III – in 13.6 % (n = 3) and IV – in 0 % (n = 0). The sensitivity and diagnostic accuracy of a complex endoscopic examination (EGDS and colon endoscopy) were higher compared with colon endoscopy alone, and amounted to 88.9 % and 55.6 %, 85.2 % and 68.5 %, respectively, and the specificity was in both cases – 81.5 %. The main clinical manifestations of HI aGVHD included symptoms such as diarrhea that is not controlled by medication (n = 17; 77.3 %), anorexia (n = 19; 86.4 %), epigastric pain (n = 22; 100 %), nausea (n = 12; 54.5 %), vomiting (n = 4; 18.2 %), melena (n = 3; 13.6 %).

Conclusion. The diagnosis of GI aGVHD is made on the basis of a comprehensive examination of patients, including clinical picture data, timing of manifestation of gastrointestinal disorders, results of immunohistochemical, microbiological, virological studies of biopsy samples of the gastrointestinal mucosa. Pediatric patients suspected of developing GI aGVHD require a comprehensive endoscopic examination (EGDS and colonoscopy), which is characterized by greater sensitivity compared to colon endoscopy alone, at the second stage of the diagnostic search after excluding viral, fungal and drug etiologies for the development of gastrointestinal disorders. Endoscopic examination must be accompanied by mandatory collection of morphological material from both changed and unchanged areas of the gastrointestinal mucosa.

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are clonal myeloid diseases characterized by hyperproduction of differentiated hematopoietic cells. Polycythemia vera (PV) belongs to the group of MPNs and is associated with a high risk of thrombosis, hemorrhagic complications and phenotypic transformation of the disease into myelofibrosis or acute myeloid leukemia. PV is extremely rare among children, first of all, when diagnosing the disease, it is necessary to exclude the secondary cause of erythrocytosis. The incidence of PV is 0.18 per 100,000 people-years the child population. Only half of pediatric patients with PV have symptoms associated with polycythemia. In most children, PV is diagnosed accidentally when an increase in hemoglobin concentration or hematocrit is noted in the full blood count. The mutation JAK2 gene is included in the diagnostic criteria of PV, but its prevalence among children is significantly lower than among adults. In adult patients with PV, the tactics of therapy were determined depending on the risk of complications of the disease: age over 60 years, a history of thrombotic complications. Children rarely have a history of thrombotic events and therefore belong to the low-risk group. Risk factors related to the prognosis and complications of the disease have not been identified for them, data on the results of сytoreductive therapy are also limited, a general algorithm for the treatment of PV in the pediatric population has not been developed, mainly the experience of therapy is extrapolated from adult clinical treatment protocols.

Relevance. The use of organ-preserving techniques has become a breakthrough in the treatment of retinoblastoma. Superselective intra-arterial chemotherapy (SIAC) belongs to the methods of local chemotherapy. It can currently be used in first-line therapy, especially for advanced unilateral tumors, and carries a lower risk for systemic toxicity. SIAC was recognized as a safe procedure with few complications. However, adverse cardiorespiratory dysfunction (CRD) such as decreased lung compliance, bradycardia and subsequent hemodynamic instability have subsequently been reported. This life-threatening condition presents as autonomic cardiorespiratory reflex or trigeminocardiac reflex. So far, no safe and effective method for their complete elimination has been found. Finding such a method is an important subject of research.

Purpose of the study – to summarize current literature data on etiology, pathogenesis, diagnosis, treatment and prevention of CRD arising during SIAC. 

Materials and methods. We searched and analyzed the literature data in the medical information systems PubMed, Chranelibrary, Cyberleninka, Google Scholar for the last 15 years using the following key words: retinoblastoma, SIAC, CRD, cardiorespiratory reflex, anesthesia during SIAC. 25 publications met the search criteria. In addition, references to selected articles were manually screened for applicable articles that included recent reports on the development of CRD during SIAC, in addition to works of historical significance.

The material is intended for a wide audience of anesthesiologists, oncologists, and ophthalmologists.

Beta-thalassemia being one of the most widespread monogenic diseases in the world is characterized by the HBB gene mutations leading to beta-globin chain decrease. Despite of the specific laboratory features diagnosis of beta-thalassemia may seem difficult especially when speaking of minor forms and carriers. The common diagnostic standard includes complete blood count with analysis of hematological indices, iron deficiency exclusion and examination of hemoglobin fractions. The last and the crucial step is providing molecular-genetic study of HBB gene as the method allowing to verify the diagnosis. The beta-thalassemia pathogenesis, comprehensive genetic classification and various laboratory diagnostics tools are discussed in this review. There exists huge knowledge about beta-thalassemia prevalence in endemic regions but little is known of beta-thalassemia incidence in nonendemic countries, e.g., Russian Federation. Nevertheless, studying beta-thalassemia prevalence in Russia remains relevant considering multi ethnicity of Russian Federation. This review presents the diagnostics algorithm with the use of HBB gene Sanger sequencing and the results of beta-thalassemia prevalence pilot research. According to the data obtained the minimal possible beta-thalassemia incidence in Moscow accounts for 0.16 %.

Extracorporeal photopheresis (ECP) has proven effective in the treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. In its standard version, ECP requires leukapheresis to obtain a fraction of mononuclear cells. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient.

In the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia was developed a new ECP method that does not require leukapheresis. This paper presents a description of two clinical cases of severe refractory GVHD treated by micro-ECP.

Neuroblastoma (NB) is the most “mysterious” tumor in pediatric oncology and predominates in the structure of cancer incidence in young patients. It should be noted that the clinical variability characteristic of this type of tumor is due primarily to its biological properties, which determine the characteristics of manifestation, response to antitumor therapy and prognosis. Today, a risk-adapted approach to the observation and/or treatment of NB using a multimodal strategy, including surgical removal of the tumor, chemotherapy/radiation/immunotherapy, is generally accepted. In addition to the molecular genetic characteristics of the tumor and the patient’s age, the key role of determining the tactics is the disease staging. Despite the fact that diagnostic algorithms are unified, including the use of various imaging methods, the issues of the greatest specificity, accessibility and associated toxicity of modern radionuclide research methods remain debatable. This article presents literature data regarding the diagnostic value of functional diagnostic methods for NB, as well as our own experience of their use in routine clinical practice.