Pediatric Hematology/Oncology and Immunopathology

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.

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.

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. Essential thrombocythemia (ET) is an orphan myeloproliferative disease with excessive platelet production associated with an increased risk of thrombosis and bleeding. Currently, there is a limited number of studies on the state of platelet hemostasis in children with ET.

Aim of this single-center prospective study was to characterize the morphological and functional properties of platelets in pediatric patients with ET.

Materials and methods. The study included 30 patients (10 boys and 20 girls) aged 3–17 years with an established diagnosis of ET. The control group consisted of 45 healthy volunteers (22 boys and 23 girls) aged 4–18 years. Flow cytometry with strong and weak activation, aggregometry, and immunofluorescence microscopy of blood smears were used to analyze platelet function.

Results. It was shown that platelets of patients with ET are characterized by a reduced size, while the number of platelet alpha and dense granules did not differ from the control group. Platelets of patients with ET showed moderate hyporeactivity in response to strong stimulation (by activation of glycoprotein IIbIIIa and secretion of dense granules). Platelet aggregation with collagen and adenosine diphosphate was also reduced in patients with ET, but these data did not correlate with the degree of platelet activation in flow cytometry.

Conclusion. Thus, characteristic morphological and functional changes in platelets were revealed in children with ET compared with the control group.

Introduction. Local inflammation commonly accompanies wounds, yet its impact on the dynamics of thrombus formation and hemostatic clot architecture remains poorly explored.

Aim: to investigate the influence of local inflammation on the dynamics of clot formation and hemostatic clot architecture.

Material and methods. In our models, we used 6–12-week-old ICR mice. Local inflammation was induced by a subcutaneous or intraperitoneal injection of hydroxyethyl cellulose gel containing lipopolysaccharide (LPS) (50 µg). Pathological thrombosis was assessed in a FeCl₃-induced carotid artery thrombosis model with fluorescence imaging. Hemostatic clots were assessed in a kidney bleeding model followed by histological staining for fibrin/fibrinogen, CD41, and nuclei.

Results. In the FeCl₃-induced arterial model, there were no significant differences between the control group and the local inflammation group (LPS group) in the time to initial thrombus formation (406 ± 189 s vs 522 ± 338 s; p > 0.05), the maximal thrombus height (560 ± 65 µm vs 650 ± 73 µm; p > 0.05), and the initial rate of clot growth (1 × 10^–4 ± 8 × 10^–5 mm²/s vs 4 × 10^–4 ± 6 × 10^–5 mm²/s; p > 0.05). However, the residual thrombus height was higher in the LPS group (250 ± 237 µm vs 595 ± 107 µm; p < 0.05). In the kidney bleeding model, the area of CD41 signal (3900 ± 1800 µm² vs 47 000 ± 44 000 µm²; p > 0.05) and the area of signal from fibrinogen (117 000 ± 33 000 µm² vs 120 000 ± 120 000 µm²; p > 0.05) did not differ between the control group and the LPS group, whereas the nuclear signal area was reduced in the LPS group (11 000 ± 9000 µm² vs 3200 ± 400 µm²; p < 0.05).

Conclusion. Local LPS-driven inflammation does not accelerate early FeCl₃-induced thrombus formation but is associated with increased thrombus persistence. In large tissue wounds, it does not measurably alter the fibrin-platelet component of the hemostatic clot while reducing nucleated cell accumulation.

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.

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 (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.

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.

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.

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.

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.