Down syndrome is a condition characterized by an extra copy of chromosome 21 resulting, among other things, in an increased susceptibility to blood disorders. Transient abnormal myelopoiesis is a unique phenomenon observed in neonates with Down syndrome. Typically, it presents in the neonatal period as a transient clonal expansion of blasts, often remaining clinically insignificant and undergoing spontaneous regression within the first 5 weeks of life. However, despite its transient nature, this condition should still be carefully monitored due to the high risk of its transformation into myeloid leukemia of Down syndrome which occurs in 20–30% of cases within the first 5 years of life. Acute myeloid leukemia and myeloid leukemia associated with Down syndrome arise from the same underlying genetic predisposition and are characterized by the proliferation of megakaryoblasts harboring a mutation in the GATA1 gene. Comprehensive assessment including morphology, immunophenotyping and cytogenetic and molecular genetic testing helps in differential diagnosis and facilitates therapeutic decision-making. Here, we present a literature review and report 2 clinical cases of transient abnormal myelopoiesis demonstrating the nature of this condition as well as its typical diagnostic features that enable prompt differential diagnosis and hence, timely initiation of supportive and cytoreductive therapy, while also highlighting the importance of careful monitoring in patients with Down syndrome.
Li–Fraumeni Syndrome (LFS) is a rare, autosomal dominant, highly penetrant cancer predisposition syndrome caused by germline mutations in the TP53 (Tumor Protein 53) gene. The classic tumor spectrum of LFS includes adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft tissue sarcomas. Hematologic malignancies (HMs) occur in 4–12% of LFS cases, with a predominance of acute lymphoblastic leukemia characterized by a specific cytogenetic variant – a hypodiploid karyotype. Myelodysplastic syndromes and acute myeloid leukemias are less common and are typically secondary to prior cytotoxic therapy. Given the unfavorable prognosis of HMs in LFS and the necessity of bone marrow transplantation as a curative treatment modality, early identification of this patient group and the selection of an optimal donor who does not carry germline TP53 mutations are of high importance. This review presents the fundamental principles of the pathogenetic basis of LFS and clinical screening criteria, providing a detailed description of the spectrum of HMs in LFS, with specific focus on the clinical and laboratory features of the most common variants.
Introduction. Essential thrombocythemia (ET) and polycythemia vera (PV) are Philadelphia chromosome-negative chronic myeloproliferative neoplasms characterized by increased megakaryocyte proliferation. Although megakaryocyte morphometry in bone marrow biopsy samples has been well studied, their morphology and distribution by maturation stages remain insufficiently investigated. The aim of our work is to study the distribution of megakaryocytes from the patients with ET and PV by maturation stages, as well as their ability to form podosomes upon contact with extracellular matrix proteins. Materials and methods. We isolated megakaryocytes from 12 patients with ET, 4 patients with PV, and 25 healthy donors using a transparent slide with immobilized monafram – the F(ab′)2 fragment of a mouse monoclonal antibody to glycoprotein IIb–IIIa. Their morphology, distribution by maturation stages, and size were analyzed. In 3 healthy donors and 3 patients with ET, we analyzed the density of podosomes formed during incubation with monafram, collagen I, and fibrinogen using fluorescent confocal microscopy (staining with fluorescently labeled phalloidin). Results. Compared with the healthy donors, the patients with ET and PV had a significantly higher proportion of mature megakaryocytes, but a lower proportion of megakaryocytes at the second stage of maturation. Megakaryocyte size in the patients with chronic myeloproliferative neoplasms was also significantly greater than in the healthy donors: in the ET patients – starting from the second stage of maturation, and in the PV patients – starting from the third stage of maturation. The density of podosomes per unit area formed by megakaryocytes on slides with immobilized monafram, collagen I, and fibrinogen in the ET patients did not differ from that in the healthy donors. Podosome density on fibrinogen exceeded that on collagen I, which is consistent with the literature data. Conclusion. Among megakaryocytes isolated from the bone marrow aspirates of the patients with ET and PV, mature forms predominate; these cells are larger than normal megakaryocytes and often have multilobulated nuclei. The actin cytoskeleton in the ET patients is not disrupted and upon cell contact with extracellular matrix proteins, forms podosomes that are similar in structure and number to those of megakaryocytes from the healthy donors.
Li–Fraumeni syndrome (LFS) is a rare autosomal dominant tumor predisposition syndrome with high penetrance. The pathogenesis of the syndrome involves germline pathogenic variants in the TP53 gene. The spectrum of cancers in LFS predominantly includes solid tumors, with hematologic malignancies occurring in only 4% of cancer diagnoses. Most patients have a family history of the disease, however, in 10–20% of cases, germline variants are de novo. The introduction of next generation sequencing into clinical practice has made it possible to describe rare cases of mosaic LFS syndrome in some patients with solid tumors. This article presents the first described clinical case of mosaic LFS in a patient with hematologic malignancy. This case demonstrates how detailed molecular genetic testing using modern diagnostic techniques can determine the true origin of a pathogenic variant in the TP53 gene. The results of treatment show that, despite existing therapeutic options, patients with hematologic malignancies and LFS, including mosaic LFS, represent a challenging therapeutic group requiring the development of specialized treatment protocols.
Currently, there are two approaches to treating hereditary enzyme deficiency – Gaucher disease: intravenous infusions of recombinant enzyme – imiglucerase, velaglucerase, or taliglucerase (enzyme replacement therapy), and substrate reduction therapy with eliglustat, the advantage of which is oral administration 1–2 times a day. International phase II/III clinical trials conducted between 2006 and 2016 demonstrated high efficacy and safety of eliglustat for adult patients with Gaucher disease type 1 without severe comorbidities. According to the results of these studies, eliglustat was approved for the treatment of Gaucher disease in the United States and the European Union in 2014. A multicenter study evaluating the efficacy and safety of eliglustat in children with Gaucher disease was initiated in 2018 and completed in December 2025. This literature review summarizes data on the mechanism of action of eliglustat, its dosing characteristics, and its potential use in patients with concomitant organ pathology. In addition, the results of a comparison of changes in Gaucher disease biomarkers during substrate reduction therapy with eliglustat and enzyme replacement therapy are presented.
Introduction. Extracorporeal membrane oxygenation (ECMO) is increasingly used in pediatric oncology patients with severe cardiac and/or respiratory failure. However, experience with this technique in this population remains limited, particularly in Russia. Materials and methods. Here we retrospectively reviewed the first 5 cases of peripheral venoarterial ECMO use in children with malignancies (4 females, 1 male) treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology from October 2024 to May 2025. The median age was 12 years. Indications, patient selection criteria, ECMO duration, complications, and outcomes were analyzed. Results. In 4 out of 5 patients, ECMO was initiated due to refractory cardiac and/or respiratory failure, and in 1 case, it was used as intraoperative support. The median ECMO duration was 5 days; the median length of stay at the Intensive Care Unit was 20 days. Four patients were successfully decannulated and subsequently discharged. One patient died due to oxygenator thrombosis. Despite the extreme illness severity at baseline (pSOFA 9, VIS 95, VVR 112), no major infectious or hemorrhagic complications occurred. Conclusion. In this paper, we reported the first Russian experience of ECMO use in children with cancer demonstrating that not only is it in principle possible but also effective, as long as a multidisciplinary approach and strict selection criteria are adopted and a trained team of specialists are on hand.
Introduction. Bilateral kidney tumors (BKT) in patients with nephroblastoma is a relatively rare clinical situation and a more complex treatment challenge. The aim of the study was to evaluate the clinical, morphological, and molecular genetic characteristics of patients with BKT. Materials and methods. A retrospective analysis was conducted of 30 patients aged 2.4 to 56.2 months with histologically confirmed nephroblastoma/nephroblastomatosis treated at the Blokhin National Medical Research Center of Oncology from September 1, 2019, to June 1, 2024. Clinical and morphological features, molecular genetic characteristics, the presence of predisposing conditions, and the extent of surgical intervention were examined. Results. The median age at diagnosis in patients with and without tumor predisposition syndrome (PS) was 25 months (range, 2.4–56.2 months) and 30 months (range, 12.6–51.1 months), respectively. The female:male ratio was 1.5:1. In 23/29 (79,3%) patients with BKT, based on molecular genetic studies, germinal mutations in genes and epigenetic disorders were detected (in most cases, mutations in the WT1 and TRIM28 genes were detected and the Beckwith–Wiedemann syndrome spectrum was diagnosed). A statistically significant effect of the histological variant of nephroblastoma and PS was observed: WT1 patients had predominantly stromal histology, TRIM28 patients had epithelial histology, and patients with Beckwith–Wiedemann syndrome spectrum had predominantly regressive nephroblastoma (p 0.001). In 70% of cases, the main clinical sign indicating a renal tumor was abdominal enlargement and/or the presence of a tumor in the abdominal cavity. Stage V disease was diagnosed in 80% of children, and stage IV (metastatic lung disease) in 20%. After 6 weeks of VA therapy, 12/30 (40%) patients required additional courses of polychemotherapy using the VA and Carbo/Eto regimens according to the UMBRELLA SIOP-RTSG 2016 protocol. In 2/12 (16.7%) patients, negative dynamics were observed with tumor growth during specialized treatment; both patients had bilateral stromal nephroblastoma. Surgical treatment in most cases involved bilateral nephron-sparing surgery (22/30; 73.3%), and only 6 cases were microscopically classified as R1 resections. The local stage at which the patient subsequently received therapy was stage I in most cases (60%). Three-year overall survival and event-free survival were 93.3% and 87.8%, respectively. Four events were recorded: one local recurrence and three deaths (one due to disease progression, one due to infectious complications, and one due to early postoperative pulmonary embolism). Conclusions. BKT is a rare condition requiring a multidisciplinary approach. Additional courses of chemotherapy according to the UMBRELLA SIOP-RTSG 2016 protocol improve the response to therapy in most cases, reducing tumor size and increasing the likelihood of organ-preserving surgery. In cases of lack of response to chemotherapy or disease progression, surgical treatment is considered. Surgical treatment should be performed in specialized centers. Genetic counseling is necessary to exclude BKT. There is a correlation between the histological variant of nephroblastoma and PS.
Aim of the study: to determine the effectiveness of endovascular treatment methods for hypervascular tumors in children and to investigate complications associated with such treatment. Materials and methods. From 2012 to 2024, a total of 207 endovascular embolization procedures for various head and neck tumors in children were performed at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Healthcare of the Russian Federation. Embosphere microspheres with a diameter of 500–700 μm, hydrogel cylinders, endovascular adhesives such as ONYX 18 and cyanoacrylate, and embolization coils were used as embolization agents. The most common embolization procedure was preoperative embolization, followed by surgery within 24–48 h. However, in some cases, embolization was applied as an independent treatment method. Results. The blood supply of head and neck hypervascular tumors depends on their location. In the majority of cases, it is the facial and maxillary arteries supply. Tongue tumors are supplied by the lingual arteries. Tumors of the periorbital region and nasal bridge are supplied by the angular and ocular arteries. Complete embolization of infantile hemangiomas was achieved in 87% of the cases. Conclusion. Endovascular embolization was most commonly used in patients with arteriovenous malformations; it was performed both as an independent treatment option and in combination with surgery. In patients with hypervascular tumors, endovascular embolization was used preoperatively to reduce blood loss.
Introduction. Acute myeloid leukemia (AML) is the second most prevalent type of blood malignancy in children that accounts for 15–20% of all pediatric leukemia cases. Before 2018, large-scale prospective studies of AML in children in the Russian Federation were constrained by the absence of both a central pathology review system and centralized monitoring of minimal residual disease (MRD). To address these issues, the national protocol AML-MRD-2018 (NCT03846362) was developed and initiated by the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Materials and methods. This study included 631 patients from 54 clinical facilities across 48 regions of the Russian Federation. Central pathology review was performed at two institutions: the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow) and Yekaterinburg Regional Children's Clinical Hospital. Risk group stratification was performed in two steps: initially it was based on molecular and genetic characteristics of blast cells, and then (for intermediate risk group) – on response to treatment assessed by MRD testing. Criteria for primary refractoriness and the transfer of patients to a high-risk group were blast cell count (assessed morphologically and immunophenotypically) 5% after induction and MRD ≥ 0.1% after the first course of consolidation. The final stratification was as follows: 67 standard-risk patients, 251 intermediate-risk patients, and 313 high-risk patients. Results. Response to induction therapy was assessable in 580 patients; complete remission was achieved in 84.3% of the cases (n = 489). Treatment effectiveness varied significantly across the risk groups: it was 100% in the standard-risk group (all the patients achieved MRD-negative remission), 91.5% in the intermediate-risk group and 72.9% in the high-risk group (which had the highest proprotion of refractory and MRD positive patients). The first cycle of consolidation therapy according to the protocol was given to 385 patients from the intermediate- and high-risk groups; MRD assessment was performed in 348 cases. MRD-negative remission was achieved in 196 (96%) out of 204 MRD-assessed patients in the intermediate-risk group and in 129 (90%) out of 144 MRD-assessed patients in the high-risk group. The 3-year treatment outcomes in the whole cohort of patients (n = 631) were the following: the overall survival (OS) reached 71% (95% confidence interval (CI) 68–76), the event-free survival (EFS) was 44% (95% CI 40–48), the cumulative risk of relapse (CRR) was 36% (95% CI 31–41). There were significant differences in these parameters between the risk-groups: standard-risk group (n = 67): OS – 84%, EFS – 66%, CRR – 24%; intermediate-risk group (n = 251): OS – 77%, EFS – 50%, CRR – 38%; high-risk group (n = 313): OS – 64%, EFS – 34%, CRR – 37%. Over the period of observation, a total of 255 allogeneic hematopoietic stem cell transplantations (HSCT) were performed. The most common HSCTs were from haploidentical related donors (n = 180; 70%), the graft sources were peripheral blood stem cells (n = 138) and bone marrow (n = 87). The median time from start of therapy to HSCT was 5 months. The 2-year EFS after HSCT was 65% and the 2-year OS post-HSCT was 75%. Conclusion. To date, the potential of universal chemotherapy protocols for AML has been exhausted. Further improvements in treatment outcomes are only possible through the implementation of individualized treatment strategies based on molecular genetic profiling. Promising approaches include the addition of FLT3 inhibitors, gemtuzumab ozogamicin, venetoclax; the inclusion of menin inhibitors in leukemias with KMT2A rearrangements; the integration of hypomethylating agents in the treatment of patients with CBF-AML.
Modern hematology/oncology is undergoing a transformation driven by the implementation of whole-genome sequencing (WGS) technologies. In adults, large-scale initiatives such as the Cancer Genome Atlas have provided the basis for acute myeloid leukemia (AML) molecular classification as well as for the development of targeted therapy for this disease. In pediatric hematology/oncology, the search for optimal diagnostic strategies continues: in 20–25% of children with AML, standard diagnostic tests reveal an apparently normal karyotype that may, however, often harbor unknown or cryptic driver events. These events define the unique molecular landscape of the disease dominated by structural rearrangements. Today, the use of WGS enables the identification of novel age-related molecular subtypes of the disease as well as driver aberrations, with many of them associated with unfavorable prognosis and resistance to standard treatment. This review systematically presents information on how WGS fundamentally changed our understanding of the molecular architecture of pediatric AML: from the identification of novel markers (e.g., UBTF-TD) and rearrangements leading to enhancer hijacking (BCL11B, HOX) to the revision of approaches to molecular classification and risk stratification. Here, we summarized the existing data on the diagnostic and prognostic significance of WGS in pediatric AML and discussed limitations of the clinical interpretation of findings as well as prospects for WGS integration into routine diagnostic practice.
Introduction. The cold storage of platelets at 2–6°C has a number of advantages such as bacterial growth reduction and metabolic slowdown, and may be an alternative to conventional storage at room temperature. However, the impact of cold storage on platelet function continues to cause controversy among specialists. Aim: to compare the functional parameters of platelet concentrates suspended in SSP+ additive solution when stored for 5 days under standard conditions versus in the refrigerator. Materials and methods. To assess the function of stored platelets, flow cytometry and platelet aggregation analysis using the low-angle light scattering technique were employed. Results. It was shown that the number and morphological parameters of the cold-stored platelets had not changed during the 5-day period and remained within the reference range. At the same time, spontaneous expression of P-selectin and phosphatidylserine, platelet activation markers, increased significantly, compared to standard storage conditions. When refrigerated, platelets responded better to collagen activation and their aggregation capacity also remained high. There were no significant differences in platelet desialylation between Days 1 and 5 of cold storage. Conclusion. The obtained results allow us to conclude that platelets retain their activation and aggregation capacity when stored in the cold within the standard 5-day shelf life.
Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma in children. Although outcomes are favorable after first-line therapy based on treatment regimens for acute lymphoblastic leukemia, the prognosis of patients with recurrent or refractory disease remains extremely poor, with overall survival rates of only about 50%. This article presents an analysis of factors contributing to resistance to therapy and highlights current strategies for the treatment of relapsed/refractory lymphoblastic lymphoma.
Human cells are capable of switching between several modes of functioning: active proliferation, quiescence (autophagy), senescence, apoptosis, and others. This switching plays numerous roles in morphogenesis and development, the body's adaptation to adverse conditions and response to injuries and diseases. Disregulation of cellular switching underlies many hematological, oncological, and immunological diseases. However, for different cell types, the physiological meaning (as well as the mechanism and cellular phenotype) of many modes, such as apoptosis and aging, can be totally different. This review attempts to shed light on this issue: first, we will examine the classical hierarchy of cellular switching, which has been developed for long-lived, proliferating somatic cells, and then compare it with what is known for mobile, not necessarily somatic, cells. The existing data indicate that long-lived, fully functional cells (including stem and immune cells) have similar mechanisms, while short-lived, terminally differentiated blood cells (platelets, neutrophils, erythrocytes) are radically different. Even if they have a caspase-dependent cell death pathway, it cannot be considered analogous to apoptosis in fully functional cells.
Introduction. The drugs of choice for the treatment of adult patients with essential thrombocythemia (ET) include hydroxycarbamide (HC), anagrelide, interferon alpha (IFN-a), or pegylated interferon alpha (PEG-IFN-a). In a pediatric cohort, there is still no consensus regarding either the indications for treatment initiation or the choice of first-line treatment. The aim of the study was to evaluate the efficacy and safety of cytoreductive therapy in pediatric patients with ET. Materials and methods. The study included 24 patients diagnosed with ET in whom driver mutations in the JAK2 and CALR genes were verified. Interferon therapy was administered to 14 children: IFN-a (n = 2) at a dose of 2 000 000–3 000 000 IU subcutaneously 2–3 times a week; PEG-IFN-a (n = 12) at a dose of 1.5–3.0 μg/kg subcutaneously once a week. HC therapy at a dose of 10–20 mg/kg/day orally was administered to 8 children, anagrelide at a dose of 1.5–2.0 mg/day orally – to 1 child, and ruxolitinib at a dose of 30 mg/day orally was given to 1 child. The median duration of cytoreductive therapy was 24 (10.8–57.6) months. Before and during treatment as well as during follow-up, all the patients underwent following investigations: a complete blood count and biochemical blood test, the assessment of von Willebrand factor ristocetin cofactor (VWF:RCo) activity and allele burden, as well as ultrasound examination of liver and spleen. Results. Before the initiation of cytoreductive therapy, platelet counts were extremely high in all the patients, with a median of 1427.5 (1134.5–2161.2) × 109/L; a reduced VWF:RCo activity ( 50%) was observed in 23 out of 24 children. Thirteen (54.2%) out of 24 patients had a response to cytoreductive therapy: a complete response was achieved in 5 cases (PEG-IFN-a – 4, HC – 1); a partial response was achieved in 8 patients (IFN-a/PEG-IFN-a – 5, HC – 2, anagrelide – 1). A decrease in platelet count was observed in 20 (79.2%) out of 24 patients: 10 (83%) out of 12 patients achieved a decrease in platelet count with PEG-IFN-a; 1 (50%) out of 2 children – with IFN-a; 8 (100%) children – with HC, and 1 (100%) child – with anagrelide. In the patient treated with anagrelide, normalization of platelet count was achieved 15 months after the initiation of treatment (from 2345 to 266 × 109/L). Treatment with ruxolitinib during 6 months resulted only in a slight decrease in platelet count (from 1342 to 987 × 109/L). The restoration of VWF:RCo activity occurred in parallel with a decrease in platelet count. Eight (66.7%) out of 12 patients treated with PEG-IFN-a showed a significant reduction in allele burden, and a minor increase was observed only in 2 cases. In 2 patients, the mutant allele frequency remained unchanged compared with that before cytoreductive therapy. Two patients treated with IFN-a also showed a decrease in allele burden. The median VAF (variant allele frequency) before the initiation of cytoreductive therapy with PEG-IFN-a was 12.8% (8.7–30.5%), and after treatment during 3–100 months (median 42 months) – 10.5% (6.5–25.2%) (p = 0.02). During HC therapy, an increase in VAF was observed in 3 out of 8 patients, in 1 case VAF remained unchanged, and only 4 children showed a decrease in VAF. During PEG-IFN-a therapy, adverse side effects in the form of influenza-like illness were observed only in 1 (8.3%) out of 12 patients, whereas during IFN-a therapy – in both patients (100%). In all cases, side effects did not exceed Grade 2 according to the CTCAE v.6.0 and did not require discontinuation of therapy. As regards the patients treated with HC, adverse side effects in the form of nausea were observed in 1 (12.5%) out of 8 patients. Conclusion. When indicated, it is reasonable to use PEG-IFN-a as first-line therapy due to its high efficacy and favorable tolerability and safety profile.
Introduction. Establishing the cause of hereditary hemolytic anemia (HHA) is necessary not only for an accurate diagnosis but also for choosing a treatment strategy. Deficiencies of red blood cell glycolytic enzymes, primarily pyruvate kinase (PK), but also less common deficiencies of glucose phosphate isomerase (GPI) and hexokinase (HK), are among the causes of HHA. According to international standards, confirmation of a deficiency of a glycolytic enzyme is the presence of mutations in the gene encoding the enzyme and direct measurement of its decreased activity in red blood cells. However, genetic testing is currently not always available in Russia, and results are typically delayed. Regarding the determination of the activity of these enzymes, testing for their activity has not yet been introduced into clinical practice in Russia. Aim: this study focuses on the development of methods for analyzing the activity of glycolytic enzymes (PK, GPI, and HK). Their implementation in clinical practice will help improve the accuracy of differential diagnosis of HHA caused by enzymopathies. Materials and methods. Blood from healthy donors and patients with HHA of various etiologies was analyzed. Activity results were expressed as international units per gram of hemoglobin (IU/g Hb). PK, GPI, and HK activities were measured in erythrocyte hemolysates by spectrophotometric methods using coupled biochemical reactions resulting in a change in the optical density of the reaction sample at a wavelength of 340 nm. Results. Methods for analyzing the enzymatic activity of PK, GPI, and HK in erythrocytes were developed, taking into account all conditions affecting the accuracy of the analysis. The activities of these enzymes were measured in red blood cells of the patients with different hemolytic anemias and donors: PK – n = 452 and n = 95, HK – n = 113 and n = 53, and GPI – n = 7 and n = 30, respectively. The reference intervals of normal values of these activities in erythrocytes were calculated (medians and regions including 2.5% to 97.5% of all the measured values): PK – 10.85 (8.41; 16.42) IU/g Hb (n = 95), HK – 0.90 (0.68; 1.11) IU/g Hb (n = 53), GPI – 44.22 (34.31; 62.35) IU/g Hb (n = 30). It was shown that the activity of these enzymes in the erythrocytes of the patients with a genetically proven defect in the structure of these enzymes and no recent donor red blood cell transfusions was reduced. Conclusion. The developed biochemical methods for measuring the activity of glycolytic enzymes (PK, GPI, and HK) are highly sensitive and specific. Their use significantly facilitates the differential diagnosis of HHA caused by glycolytic enzyme deficiencies, bringing this diagnostic approach into line with international standards.
Aim: to analyze current data on the safety of nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol in children with oncological and hematological diseases considering the specific risks of this patient population. Materials and methods. We conducted a systematic literature review in PubMed, Cochrane Library, Web of Science and eLIBRARY databases, from 2020 to 2025, using the following keywords: “pediatric oncology”, “pediatric hematology”, “nonsteroidal anti-inflammatory drugs”, “paracetamol”, “acetaminophen”, “safety”, “thrombocytopenia”, “febrile neutropenia”, “drug interactions”, “pain”. Results. The main risks of using NSAIDs and paracetamol in pediatric hematology/oncology were identified: hemorrhagic complications in patients with thrombocytopenia (individuals with platelet count 50 × 10⁹/L have a 2.5–4.0-fold increased risk), drug interactions with chemotherapy agents (especially with methotrexate), paracetamol-induced hepatotoxicity (elevated levels of alanine aminotransferase/aspartate aminotransferase in 15–25% of patients), renal toxicity of NSAIDs (acute kidney injury in 8–12% of patients). Safe dosages were established and clinical monitoring guidelines were developed. Paracetamol remains the treatment of choice in thrombocytopenia because it does not cause platelet aggregation. Conclusion. The use of NSAIDs and paracetamol in pediatric hematology/oncology requires an individualized approach that would take into account patient’s hemostatic parameters, hepatic and renal function, ongoing chemotherapy and potential drug interactions. There is a need for further studies of the long-term safety of these drugs in this cohort of patients and for the development of clear clinical guidelines for their use.
Introduction. Osteosarcoma of the maxillofacial region is an extremely rare variant of osteosarcoma, accounting for no more than 6–9% of all cases. Unlike tumors located in the bones of the extremities, osteosarcoma of the maxillofacial region is characterized by a lower tendency for distant metastasis. Due to the specific location of the primary lesion in the maxillofacial region, namely the proximity to vital structures, radical surgical intervention is associated with a number of difficulties; however, it is a key element of treatment that determines the prognosis of the disease. Materials and methods. The study included patients under the age of 18 years with a verified osteosarcoma of the maxillofacial region, registered between 2012 and 2024 at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Healthcare of the Russian Federation. Treatment for high-grade osteosarcoma patients was conducted according to the MAP regimen (based on the EURAMOS-1 protocol). Treatment for low-grade osteosarcoma patients was limited to surgical resection of the primary lesion. Results. The study included 11 patients (6 boys and 5 girls) with a median age of 11 years. Seven tumors (63.6%) were located in the mandible and four tumors in the maxilla (36.4%). A histological examination revealed 9 (81.9%) cases of high-grade osteosarcoma and 2 (18.1%) cases of low-grade osteosarcoma. The stage distribution was as follows: stage IA, 18.1%; stage IIA, 63.6%; stage IIB, 9.0%; stage III, 9.0%. Local surgical control was performed in all the patients: R0 resection was achieved in 9 (81.9%) cases and R1 in 2 (18.1%) cases. The median follow-up was 7 years. The event-free survival was 91% at 1 year and 64% at 3 years and at 5 years. The overall survival was 100% at 1 year, 82% at 3 years, and 73% at 5 years. Conclusion. The cornerstone of treatment for patients diagnosed with osteosarcoma is radical surgery. In patients, for whom radical resection is not feasible, survival approaches zero.
Introduction. The (1;19)(q23;p13) translocation, which generates the TCF3::PBX1 fusion gene, is detected in 3–5% of patients with acute lymphoblastic leukemia (ALL). In cases of relapse, the disease often demonstrates aggressive and refractory behavior, including the development of extramedullary sites. Defining the optimal sequence and combination of therapeutic approaches in this genetic subgroup requires further investigation and standardization on the basis of accumulated clinical data. Aim: to describe the clinical patterns of ALL relapse in children with the (1;19)(q23;p13) translocation and to analyze outcomes according to relapse site and disease course. Materials and methods. We conducted a retrospective descriptive analysis of seven pediatric ALL relapse cases harboring the (1;19)(q23;p13) translocation. We analyzed the clinical manifestations of relapses, the sequence of salvage therapy, and outcomes at last follow-up. For a more detailed analysis, two cases with opposite outcomes were selected: one with a durable second remission and another with a progressive, incurable disease. Results. At the time of analysis, sustained remission was achieved in only 1 out of 7 patients. In 3 cases, treatment options were exhausted and these patients were transitioned to a palliative level of care. At the time of manuscript preparation, 2 patients were undergoing hematopoietic stem cell transplantation, and 1 patient was receiving maintenance therapy. Conclusion. This case series highlights the need for individualized management of relapsed ALL in this genetic subgroup, including targeted and cell therapies, local control strategies, and updating risk stratification models.
This article is a review of the current literature on the molecular and genetic features of mature B-cell non-Hodgkin lymphomas (B-NHL) in children. This group of lymphoproliferative neoplasms is characterized by relative similarity in morphological and immunophenotypic features while exhibiting pronounced heterogeneity at the molecular and genetic level. Recent studies have enabled the identification of distinct biological subtypes of B-NHL, which has significantly changed approaches to their diagnosis and treatment. Our review examines the classification features of B-NHL in children, as well as key molecular genetic abnormalities and oncogenic signaling pathways responsible for the development of this group of diseases. This article also highlights the need for pediatric-specific studies of B-NHL and the development of specialized diagnostic and therapeutic approaches is emphasized.
Introduction. Since 2017, the Russian Primary Immunodeficiency Registry managed by the National Association of Experts in Primary Immunodeficiencies (NAEPID) has been systematically collecting data on patients with inborn errors of immunity (IEI) making it possible to assess the effectiveness of diagnosis and treatment of these patients. The aim of the study was to analyze data from the Registry and to report changes in key epidemiological parameters collected over a period from 2015 to 2025, with an assessment of the impact of modern diagnostic tools and active educational efforts of the NAEPID. Materials and methods. We conducted a retrospective study using anonymized data of patients included in the NAEPID Registry before 30.06.2025. We analyzed changes in prevalence and mortality rates over time by taking into account demographic characteristics and type of condition. Results. Our analysis included data from 6026 patients: 5499 (91.3%) alive and 527 deceased (8.7%). Over the past 10 years, mortality has declined by 60%, from 16.3 to 6.5 per 1000 children. However, the mortality profile by age and type of disease remained stable, with the majority of fatal cases (up to 54%) occurring in the first five years of life among patients with combined IEI. In 2024, IEI prevalence reached 3.76 per 100 000, which is 2.8 times higher than in 2020, with regional variability from 2.17 to 4.27 per 100 000. Over the past five years, the number of newly diagnosed adults has been steadily increasing, accounting for 16–22% of all new cases annually. Following the inclusion of IEI in the newborn screening (NBS) program, the percentage of cases detected through NBS comprised 19% of all new IEI diagnoses and 35% and 33% of pediatric cases diagnosed in 2023 and 2024, respectively. Over the last five years, the number of children diagnosed with IEI before one year of age has risen significantly (1.7-fold; p 0.001) due to new possibilities in diagnosing severe combined immunodeficiency, agammaglobulinemia, and some combined IEIs with syndromic features in the first weeks of life. Conclusion. Despite a decade-long trend of steady growth of newly diagnosed cases of IEI, a decline in mortality, and better diagnosis and treatment, particularly for severe combined immunodeficiency and agammaglobulinemia, there are still a number of issues that require further investigation.
