Background: An infantile hemangioma (IH) is a benign lesion that develops as a result of pathologically dysregulated proliferation of the endothelial cells of the capillaries, typically appearing within the first three years of life. The disease is found mostly on the skin and—less often—in the internal organs. Although IH generally has a good prognosis and may sometimes undergo spontaneous regression, certain types of IH with a specific form, localization, and size may lead to life-threatening conditions including impairment of vital functions. This determines the need for precise diagnostics and treatment. Case presentation: The paper presents a clinical observation of an infant in the first months of life with IH presenting as diffuse hepatic hemangiomatosis and a hemangioma of the left eyebrow area. The IH was associated with life-threatening conditions. However, effective treatment with the non-selective β-adrenoblocker propranolol led to a positive outcome and the resolution of complications. Conclusions: This case demonstrates the critical importance of timely diagnosis and treatment for lesions that, while benign, can lead to fatal complications if not addressed promptly.

Background: Anaplastic large cell lymphoma (ALCL) accounts for up to 15% of all pediatric and adolescent non-Hodgkin lymphomas and is characterized by significant clinical, morphological, and immunohistochemical heterogeneity. Expression of T-cell markers on tumor cells is considered as one of the factors in an unfavorable prognosis in ALCL. However, no treatment protocols based on ALCL immunological heterogeneity have been used, yet. Objective: To compare the effectiveness of immunophenotype-oriented chemotherapy in children with ALCL treated according to the ALCL NII DOiG 2003 protocol versus the standard NHL-BFM 95 protocol. Methods: A retrospective-prospective analysis of 100 newly diagnosed ALCL patients, who were treated between 2000 and 2023, was performed across five pediatric oncology and hematology centers in Russia. Patients were divided into two groups: those treated with the NHL-BFM 95 protocol (n = 52) and those treated with the ALCL NII DOiG 2003 protocol (n = 48). Comparative analysis used Kaplan-Meier survival curves constructed for each group, and statistical analysis was performed with IBM SPSS Statistics 21.0. Results: The 10-year overall survival was significantly higher in the ALCL NII DOiG 2003 group (95.3 ± 3.3%) compared to that of the NHL-BFM 95 group (82.0 ± 5.4%, p = 0.037). Event-free survival was also improved (95.3 ± 3.3% vs. 68.6 ± 6.5%, p = 0.001), as well as the relapse-free survival (97.3 ± 2.7% vs. 74.4 ± 6.4%, p = 0.003). Conclusions: The immunophenotype-oriented approach of the ALCL NII DOiG 2003 protocol provides significantly improved long-term outcomes compared to the common NHL-BFM 95. These findings support the benefit of personalized immunologically targeted therapy in pediatric ALCL treatment.

Acute lymphoblastic leukemia (ALL) in children and adolescents is one of high curable malignancy with long-term survival rate 91 %. Nevertheless, patients with high risk of relapse / refractory ALL have event-free survival not exceed 55 %. For therapeutic efficacy improvement in patients with high risk ALL, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is used. Improvement of ALL therapy by targeted and molecular oriented drugs (imatinib mesylate, dasatinib, blinatumomab, inotuzumab ozogamycin), extension of therapeutic options for patient care in the post-transplant period are changed indications for allo-HSCT. In the current issue a modern indications for allo-HSCT in patients with primary diagnosed ALL, based on cytogenetic, molecular biologic, and clinical characteristics by the leading research groups AIEOP / BFM (Italy / Germany), St. Jude (USA), COG (USA) are presented. In spite of presented differences, common indications for allo-HSCT are minimal residual disease persistence in postinduction period in combination with cytogenetic, molecular and biologic factors of unfavorable prognosis.

Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common malignant disease in children. Contemporary antitumor treatment protocols provide long-term survival rates in over 90% of patients with ALL. High effectiveness of the treatment has been achieved as a result of chemotherapy optimization, use of targeted drugs, up-to-date genetic information, and detection of minimal residual disease (MRD). Current highly sensitive methods for MRD detection have advantages and disadvantages, and the challenge is to distinguish between false-positive and false-negative tests. Methods: A comprehensive search through MEDLINE, PubMed, Scopus, and ScienceDirect using the MRD-related keywords was performed, and included a final set of 72 academic articles. Results: At present, flow cytometry for MRD detection provides the necessary sensitivity of 10−4 and allows for reliable prediction of ALL dynamics and effective therapeutic strategies. However, even multicolor flow cytometry (MFC) cannot avoid cases of false-positive or false-negative results. Highly sensitive and productive genomic methods in addition to MFC may enhance the accuracy of MRD evaluation. On the other hand, overwhelming efforts to reach the highest sensitivity of the detection methods may lead to the detection of clinically insignificant manifestations of minimal residual disease and, subsequently, to unjustified escalation of antitumor therapy. Conclusions: The necessary ground for an adequate sensitivity of the MRD detection methods could ensure the fine line between false-positive and false-negative MRD results in patients with childhood ALL to develop an appropriate therapeutic strategy.

Background/Objectives: Glucocorticoids (GCs) present effective anti-cancer drugs for the treatment of hematological malignancies but their clinical use is limited due to their multiple adverse effects. Selective glucocorticoid receptor agonists/modulators (SEGRAMs) modify glucocorticoid receptor (GR) function shifting it towards therapeutically important transrepression and, therefore, could be safer alternative to GCs. Here we report on biological activity of four novel ligands of glucocorticoid receptor (GR), derivatives of natural origin molecule, synephrine. Methods: We demonstrated the affinity of synephrine derivatives in silico and in vitro by molecular dynamics simulation and radioligand binding assay, correspondingly. Further, we tested the induction of apoptosis in cultured cells and cytotoxic effects in primary lymphoblasts from the patients with acute lymphoblastic leukemia. Therapeutically important GR transrepression was evaluated by luciferase reporter assay and Q-PCR of transrepression marker genes, while GR transactivation associated with side effects was evaluated by Q-PCR analysis and by the level of GR phosphorylation at Ser211. Anti-cancer effects of leader compound, 1-[4-(benzyloxy)phenyl]-2-(hexylamino)ethanol (10S-E2), was studied on murine transplantable lymphoma P388 model. 10S-E2 potential to avoid the development of atrophic complication was evaluated on the murine model of glucocorticoid-induced osteoporosis. Results: All studied synephrine derivatives demonstrated high GR affinity; the effects on GR function were controversial. The leader compound, 10S-E2 revealed SEGRAM properties in vitro and demonstrated anti-cancer effects in vivo. Conclusion: Although the anti-cancer effect of 10S-E2 was less pronounced to the reference drug dexamethasone, non-atrophogenic properties of 10S-E2 make this molecule an attractive candidate for long-term GR-associated therapies.

Glucocorticoids are widely used in the therapy of inflammatory and autoimmune disease as well as cancer. They realize the therapeutic effects via cytotoxic action on the immune cells; however, glucocorticoids are characterized by multiple severe side effects including metabolic and atrophic complications as well as glucocorticoid resistance development. With the progression in the field of steroid research and their mechanism of action, several steroid and non-steroid GC analogues with decreased adverse effects were developed for potential treatment on cancer, inflammatory and autoimmune diseases. Therefore, the important criteria of the evaluation of the efficacy of such molecules is the proof-of-concept studies in vivo on the proper models of the main disease as well as potential GC-related side effects. Here we summarized the current experience of the research groups worldwide in modeling of GC undesirable effects and presented the most valid animal models for studying the effects of both GC and their analogues on bone tissue, muscles, skin, as well as carbohydrate and fat metabolism. Brief summary of the fundamental mechanisms of side effect development is also provided. The presented review will be useful for the translational research of GC and their analogues in vivo.

Background. Modern therapeutic approaches to non-Hodgkin’s lymphomas (NHL) in children consider the tumor morpho-immunohistochemical features, stage and prognostic risk group. However, regardless of the protocol used, methotrexate (MTX) is recommended in high (1000–5000 mg / m2) doses at the advanced stages of NHL. Such an approach has significantly increased patient survival rates, allowing for a cure in the vast majority of patients. A serious disadvantage of MTX is a wide range of organ toxicity, which remains a clinically significant problem. A well-known factor in predicting the development of MTX toxicity is the pharmacokinetic parameter – delayed excretion of MTX, which increases the duration of drug exposure and causes increased manifestations of organ toxicity. Interindividual variability in toxicity may be partly due to the polymorphisms of genes involved in MTX metabolism. Currently published data are often contradictory, so further research in this area is relevant. Aim. To determine the effect of pharmacogenetic markers on the risk of developing MTX organ toxicity in pediatric patients with different NHL variants. Materials and methods. From 2020 to 2024, the study included 103 pediatric patients (2 to 18 years old), who, according to the clinical guidelines of the Ministry of Health of Russia, were verified as having one of the NHL variants and initiated antitumor treatment according to chemotherapy protocols with high-dosed MTX. Genetic testing using the allele-specific hybridization method on a biological microchip was performed on all patients. The material for the study was DNA from peripheral blood lymphocytes. The time of blood sampling is not regulated. The polymorphisms of folate cycle and drug metabolism genes (MTHFR, MTR, MTRR, SLC19A1, CYP2B6, CYP4F8, SULT1E1, SLCO1B1) was determined, as well as the spectrum and degree of toxic effects were assessed using the toxicity scales of the National Cancer Institute (USA), and statistical analysis of the distribution of features and the degree of association were performed. Results. A significant association of delayed MTX excretion with the AA genotype of SLC19A1 rs2838958 was revealed. The AA and GA genotypes of the MTHFR rs1801133 polymorphism were found to be a predisposition factor to severe mucositis. The AA and GA genotypes of the SLC19A1 rs2838958 polymorphism, and the CC genotype of CYP2B6 rs4803418 and CC CYP2B6 rs4803419 are determined as risk factors for the severe infectious complications development. Conclusion. Individual characteristics of the patient’s organism, which are determined, among other things, by the variability of genes involved in drug metabolism, can affect the MTX pharmacokinetics, as well as degree and spectrum of organ toxicity. Information on genetic polymorphisms can become a tool for personalizing MTX therapy, adapting the dose of the drug or the protocol of supportive care to personal genetic patients features.

Glucocorticoids (GCs) represent effective anti-cancer drugs for the treatment of hematological malignancies, but their clinical use is limited due to their multiple adverse effects. Selective glucocorticoid receptor agonists/modulators (SEGRAMs) modify glucocorticoid receptor (GR) function, shifting it towards therapeutically important transrepression and, therefore, could be safer alternative to GCs. Here we report on the biological activity of four novel glucocorticoid receptor (GR) ligands, derivatives of synephrine, a natural-origin molecule. We demonstrated the affinity of synephrine derivatives in silico and in vitro by molecular dynamics simulation and radioligand binding assay, correspondingly. Further, we tested the induction of apoptosis in cultured cells and cytotoxic effects in primary lymphoblasts from patients with acute lymphoblastic leukemia. Therapeutically important GR transrepression was evaluated by luciferase reporter assay and Q-PCR of transrepression marker genes, while GR transactivation associated with side effects was evaluated by Q-PCR analysis and by the level of GR phosphorylation at Ser211. Anti-cancer effects of the leader compound, 1-[4-(benzyloxy)phenyl]-2-(hexylamino)ethanol (10S-E2), were studied using a murine transplantable lymphoma P388 model. The potential of 10S-E2 to prevent the development of atrophic complication was evaluated using a murine model of glucocorticoid-induced osteoporosis. All studied synephrine derivatives demonstrated high GR affinity, with the IC50 value of the most active derivative 10S-E2 being 0.56 µM; the effects on GR function were cell-type-specific. The leader compound, 10S-E2, revealed SEGRAM properties in vitro and demonstrated anti-cancer effects in vivo, inhibiting tumor growth by more than 60%. Although the anti-cancer effect of 10S-E2 was less pronounced than that of the reference drug dexamethasone, non-atrophogenic properties of 10S-E2 make this molecule an attractive candidate for long-term GR-associated therapies.

Background. Phacomatosis pigmentokeratotica (PPK) is an orphan genodermatosis from the epidermal nevus syndrome group. This disease is caused by somatic mosaicism predominantly in the HRAS gene. Pathognomonic PPK sign is combination of congenital linear nevus sebaceus of Jadassohn and speckled lentiginous nevus. Second one may debut much later. In some cases, there are signs of nervous system damages, skeletal disorders, visual impairments. Case description. Description of a patient with PPK and novel for this disease mosaic variant G469A in the BRAF gene is presented. Clinical picture included typical signs of the syndrome and immunological disorders unusual for patients with PPK. Possible genotype-phenotype correlations were analyzed based on 16 previously published observations of genetically verified PPK. Conclusion. The syndrome rarity, its course variability, and patients genetic testing features determine the difficulties in PPK diagnosis. The disease should be considered not only in terms of dermatological signs, but also regarding comorbid disorders. The dynamic follow-up should include consultations of pediatric oncologist, neurologist, ophthalmologist, endocrinologist, orthopedist, cardiologist, and immunologist.

Introduction . The acute lymphoblastic leukemia (ALL) therapy programs developed by the BFM group (Berlin-Frankfurt-Munster) are used to treat lymphoblastic lymphomas from precursor cells (LBL) and are the most effective treatment methods in the world. Aim . To assess the treatment results of LBL in children according to the ALL IC-BFM 2002/2009 protocols in a clinical trial of a single center. Materials and methods . From 2002 to 2022 a retrospective and prospective study included 70 patients aged 2 to 17 years with newly diagnosed LBL, with a median age of 9.4 years. There were 1.5 times more male patients than female (43:27). LBL from T-cells progenitor (T-LBL) was diagnosed in 61 patients (87 %), and LBL from B-cells progenitor (B-LBL) — in 9 (13 %). 59 (84.3 %) patients were included in the intermediate risk (IR) group and 11 (15.7 %) patients — in high-risk (HR) group. There were no patients in the study cohort who met the criteria of the standard risk group (SR). Results . The 10-year OS in the group of patients treated according to the ALL IC-BFM 2002/2009 protocols was 95.4 ± 2.6 %; the 10-year RFS — 91.9 ± 4.9 %; the 10-year EFS — 86.7 ± 5.6 %. When analyzing survival rates depending on the prognostic risk group, the 10-year OS for patients of the intermediate risk group was 96.6 ± 2.6 %, and for patients of the high-risk group — 90.9 ± 8.7 %. Conclusions . The obtained results confirm the high effectiveness of the ALL IC-BFM 2002/2009 protocols in the treatment of LBL.

Follicular lymphoma is one of the most common non-Hodgkin’s lymphomas in adults. One of the rather rare variants of follicular lymphoma is pediatric follicular lymphoma. This variant, despite the name, is diagnosed not only in children, but also among young adults. Pediatric follicular lymphoma is characterized by early (I, II) stages, the absence or weak BCL2 expression, and the predominant absence of t(14;18)(q32;q21) translocation. Treatment tactics vary widely from radical surgical tumor resection with subsequent follow-up to chemoimmunotherapy with rituximab.This article presents a clinical case of advanced pediatric follicular lymphoma (stage III) in a 5-year-old patient. Using a combined treatment approach (surgery followed by immunochemotherapy) allowed to achieve a complete metabolic response which lasts more than a year.

Introduction. Lymphomatoid papulosis is a CD30-positive lymphoproliferative disease with primary skin lesions. One of the therapeutic options is the use of anti-CD30 monoclonal antibody brentuximab vedotin. Aim - to present the clinical observation of the effective treatment of lymphomatoid papulosis in a 6-year-old patient using brentuximab vedotin. Main findings. In patient K., 6 years old, after suffering from acute respiratory viral infection, the appearance of rashes was noted, located mainly on the skin of the extremities, represented by single inflammatory papules of round shape, up to 6-8 mm in diameter, dense consistency upon palpation, with a smooth surface and a pinpoint area of white necrosis in the center of individual elements. A biopsy of one of the elements was performed. According to histological examination, a diagnosis was established: lymphomatoid papulosis, type A. Due to the ineffectiveness of therapy using topical glucocorticosteroids, oral administration of prednisolone, the patient was treated with brentuximab vedotin. A partial complete response was achieved.

Clinical, morpho-immunological and cytogenetic characteristics of malignancies are very polymorphic. And no less heterogeneous are paraneoplastic skin presentations arising before malignant tumour manifestation and/or proceeding in parallel. In the current literature review the most common paraneoplastic dermatosis are presented: pyoderma gangrenosa, dermatomyositis, paraneoplastic pemphigus, pityriasis rubra pilaris, Bazex syndrome, necrolytic migratory erythema, ptyriasis rotunda, Sweet syndrome. It is provided modern concepts in pathogenesis, clinical features and treatment approaches.

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.

Background. A significant advancement in the treatment of high-grade aggressive non-Hodgkin’s lymphomas and acute lymphoblastic leukemia is the inclusion of high-dose (1000–5000 mg/m2) methotrexate in the treatment protocol. This approach has significantly increased the long-term survival rate, but it has been associated with toxicity, requiring supportive care. Factors that predict toxicity were identified, including genes involved in the metabolism (MTHFR) or transport (SLCO1B1) of methotrexate. The analysis of methotrexate metabolism has identified additional genes responsible for the elimination of this drug, allowing for more effective prevention and treatment of methotrexate-associated toxicity.Aim. To study the genetic polymorphisms of enzymes involved in the methotrexate metabolism and associated toxicity in the treatment of pediatric acute lymphoblastic leukemia and non-Hodgkin’s lymphomas.Materials and methods. Data were analyzed in specialized medical databases such as Pubmed, Scopus, Web of Science, Frontiers, and Google Scholar from 2001 to 2024.Results. The main predictors of high-dose methotrexate-associated toxicity are gene polymorphisms in MTHFR, SLCO1B1, ARID5B.Conclusion. Despite the contradictory data presented in the literature, it is important to consider the detection of polymorphisms during high-dose methotrexate treatment in order to administer timely supportive care and prevent significant toxicity.

The development of highly effective protocols for the treatment of acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphomas (NHL) followed the path of escalation of doses of cytostatic agents and improvement of supportive care. Methotrexate (MTX), used in high doses (1000–5000 mg/m2), radically changed the results of treatment of ALL and NHL in children, increasing patient survival rates. The downside of the anti-tumor effect of MTX is its organ toxicity, and therefore the development of methods for predicting the development of toxic effects of MTX is an important scientific and practical task. In recent years, the genetic factors of the patient’s organism have been considered as one of the reasons for the individual variability of pharmacokinetic and pharmacodynamic parameters of MTX. Abnormal function of folate cycle enzymes, methotrexate transporter proteins, due to gene polymorphism, may affect the effectiveness and toxicity of the drug. This review summarizes and analyzes the known genetic polymorphisms involved in MTX metabolism. The possibilities of predicting toxicity, as well as the prospects for individualizing therapy, taking into account the results of pharmacogenetic testing, are presented.

Treatment intensification of acute lymphoblastic leukemia in children with L-asparaginase (L-ASP) improves therapy effectiveness and shows high survival rates. The unique biological properties of this enzyme make it possible to suppress tumor blasts proliferation by reducing blood asparagine concentration. L-ASP use is limited by toxicity and hypersensitivity reactions observed in 75 % of cases. Although most complications during L-ASP therapy are mild/moderate and are manageable with adequate accompanying therapy, the development of severe side effects leads to forced withdrawal of L-ASP, which significantly reduces the likelihood of a favorable outcome in children with acute lymphoblastic leukemia. One of the most severe toxicity manifestations is the development of asparaginase-associated pancreatitis. It worsens the prognosis and may cause patients’ death. This article presents both current data about asparaginase-associated pancreatitis and treatment experience of this complication at the Research Institute of Pediatric Oncology and Hematology of the N. N. Blokhin National Research Center of Oncology.

The discovery of immune checkpoints (IC) has become a landmark event in immuno-oncolog y, improving the understanding of the mechanisms of tumor cells evading immune sur veillance. Based on this, a group of drugs such as immune checkpoint inhibitors (ICIs) were developed, the ef fect of which is due to the rupture of the immunological synapse and recognition by tumor T cells. Currently, ICIs are successfully used in the treatment of a number of malignant neoplasms, improving the indicators of diseasefree and overall sur vival. However, determining the role of these drugs in the treatment of children with tumors of the blood system is the subject of active research. This article presents a review of the literature on topical aspects of the administration of PD-1 and PD-L1 inhibitors in pediatric hematolog y. Their mechanisms of action, ef fectiveness and potential complications of therapy are presented.