Pub Date : 2024-07-23DOI: 10.24287/1726-1708-2024-23-2-208-220
O. Goronkova, A. Pavlova, E. Raykina
This article presents a brief overview of publications on pediatric aplastic anemia (AA) and closely related conditions. Here we consider the pathophysiology of AA, which includes three main mechanisms of bone marrow destruction resulting in aplasia: direct injury, immune mediated destruction and bone marrow failure resulting from inherited and clonal disorders. New aspects of inherited bone marrow failure syndromes, inborn errors of immunity and myelodysplastic syndromes are highlighted as the most common conditions included in the spectrum of differential diagnosis of AA in children. A comprehensive algorithm for the diagnosis of AA in children is presented, including standard laboratory tests and additional modern molecular and genetic techniques that contribute to a better understanding of this heterogeneous group of diseases and determine approaches to the choice of therapy. The purpose of the review is to provide pediatricians and pediatric hematologists with an updated information of this rare, heterogeneous condition based on an analysis of the latest literature data.
本文简要概述了有关小儿再生障碍性贫血（AA）及密切相关疾病的出版物。在此，我们探讨了再生障碍性贫血的病理生理学，包括骨髓破坏导致再生障碍的三种主要机制：直接损伤、免疫介导的破坏以及遗传性和克隆性疾病导致的骨髓衰竭。遗传性骨髓衰竭综合征、先天性免疫错误和骨髓增生异常综合征是儿童AA鉴别诊断中最常见的疾病。文中介绍了诊断儿童 AA 的综合算法，包括标准实验室检测和其他现代分子与遗传技术，这些技术有助于更好地了解这组异质性疾病，并确定治疗方法的选择。这篇综述的目的是在分析最新文献数据的基础上，为儿科医生和儿科血液病专家提供有关这种罕见、异质性疾病的最新信息。
{"title":"Aplastic anemia in children: the current concept of differential diagnosis","authors":"O. Goronkova, A. Pavlova, E. Raykina","doi":"10.24287/1726-1708-2024-23-2-208-220","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-208-220","url":null,"abstract":"This article presents a brief overview of publications on pediatric aplastic anemia (AA) and closely related conditions. Here we consider the pathophysiology of AA, which includes three main mechanisms of bone marrow destruction resulting in aplasia: direct injury, immune mediated destruction and bone marrow failure resulting from inherited and clonal disorders. New aspects of inherited bone marrow failure syndromes, inborn errors of immunity and myelodysplastic syndromes are highlighted as the most common conditions included in the spectrum of differential diagnosis of AA in children. A comprehensive algorithm for the diagnosis of AA in children is presented, including standard laboratory tests and additional modern molecular and genetic techniques that contribute to a better understanding of this heterogeneous group of diseases and determine approaches to the choice of therapy. The purpose of the review is to provide pediatricians and pediatric hematologists with an updated information of this rare, heterogeneous condition based on an analysis of the latest literature data.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"60 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141813069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.24287/1726-1708-2024-23-2-222-230
A. N. Sveshnikova, E. A. Adamanskaya, Yu.-D. D. Korobkina, M. A. Panteleev
The formation of extracellular DNA traps by neutrophils, or NETs (neutrophil extracellular traps) plays an essential role in many pathological processes related to hematological, oncological, and immunological diseases. This mechanism of the programmed cell death of neutrophils and other leukocytes appears to be also involved in the pathogenesis of thrombosis and thrombotic complications of a variety of disorders. In this review, we discuss the pathways of intracellular signaling leading to neutrophil activation in thrombosis and hemostasis. Even though the biochemical reactions in a cell are quite well investigated, the regulation of activity of specific proteins involved in NETosis, such as NADPH oxidase (NOX) and protein-arginine deiminase (PAD4), requires further investigation. Current approaches to the pharmacological modulation of NETosis are also specifically addressed here.
嗜中性粒细胞形成的细胞外 DNA 陷阱或 NET（嗜中性粒细胞细胞外陷阱）在许多与血液病、肿瘤和免疫学疾病相关的病理过程中起着至关重要的作用。中性粒细胞和其他白细胞的这种程序性细胞死亡机制似乎也参与了多种疾病的血栓形成和血栓并发症的发病机制。在这篇综述中，我们将讨论在血栓形成和止血过程中导致中性粒细胞活化的细胞内信号传导途径。尽管细胞内的生化反应已被研究得相当透彻，但参与中性粒细胞增多症的特定蛋白质（如 NADPH 氧化酶（NOX）和蛋白-精氨酸脱氨酶（PAD4））的活性调节还需要进一步研究。本文还特别探讨了目前对 NETosis 进行药理调节的方法。
{"title":"Intracellular signaling involved in the programmed neutrophil cell death leading to the release of extracellular DNA traps in thrombus formation","authors":"A. N. Sveshnikova, E. A. Adamanskaya, Yu.-D. D. Korobkina, M. A. Panteleev","doi":"10.24287/1726-1708-2024-23-2-222-230","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-222-230","url":null,"abstract":"The formation of extracellular DNA traps by neutrophils, or NETs (neutrophil extracellular traps) plays an essential role in many pathological processes related to hematological, oncological, and immunological diseases. This mechanism of the programmed cell death of neutrophils and other leukocytes appears to be also involved in the pathogenesis of thrombosis and thrombotic complications of a variety of disorders. In this review, we discuss the pathways of intracellular signaling leading to neutrophil activation in thrombosis and hemostasis. Even though the biochemical reactions in a cell are quite well investigated, the regulation of activity of specific proteins involved in NETosis, such as NADPH oxidase (NOX) and protein-arginine deiminase (PAD4), requires further investigation. Current approaches to the pharmacological modulation of NETosis are also specifically addressed here.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"67 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141812708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.24287/1726-1708-2024-23-2-192-197
A. Balandina, A. D. Kuprash, N. S. Nikitin, T. A. Kovalenko, A. Ignatova, F. Ataullakhanov, M. A. Panteleev
A thrombus is a heterogeneous structure consisting of platelets in different functional states. Flow cytometry is one of the most promising tools for the diagnosis of platelet state. However, its optimization and standardization are the subjects of heated debate. How to properly activate and label platelets in order to assess their functional status? In this work, we would like to briefly highlight this issue and propose the hypothesis that several levels/types of platelet activation correspond to various positions in the thrombus and various physiological meanings. One should use this entire necessary and sufficient set of activation levels in order to draw a conclusion about how the patient’s platelets “feel”.
{"title":"The structure of hemostatic aggregate and the assessment of platelet functional activity using flow cytometry","authors":"A. Balandina, A. D. Kuprash, N. S. Nikitin, T. A. Kovalenko, A. Ignatova, F. Ataullakhanov, M. A. Panteleev","doi":"10.24287/1726-1708-2024-23-2-192-197","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-192-197","url":null,"abstract":"A thrombus is a heterogeneous structure consisting of platelets in different functional states. Flow cytometry is one of the most promising tools for the diagnosis of platelet state. However, its optimization and standardization are the subjects of heated debate. How to properly activate and label platelets in order to assess their functional status? In this work, we would like to briefly highlight this issue and propose the hypothesis that several levels/types of platelet activation correspond to various positions in the thrombus and various physiological meanings. One should use this entire necessary and sufficient set of activation levels in order to draw a conclusion about how the patient’s platelets “feel”.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"18 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141814574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.24287/1726-1708-2024-23-2-140-144
A. A. Kuznetsova, I. I. Kireev, S. Obydennyi
Platelets are the second most abundant human blood cells. They have an important function to form blood clots at sites of vascular injury to prevent bleeding. Abnormalities of platelet structure can lead to various dysfunctions and life-threatening situations. In some hereditary platelet disorders, morphological examination of platelets with transmission electron microscopy (TEM) may be required. TEM is technically complex, and its use is limited due to the need for expensive equipment and trained personnel. In our study, we assessed the morphometric parameters of platelets obtained from 20 healthy donors using TEM. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.
血小板是人体第二大血细胞。它们的重要功能是在血管损伤部位形成血凝块，防止出血。血小板结构异常可导致各种功能障碍和危及生命的情况。在某些遗传性血小板疾病中，可能需要用透射电子显微镜（TEM）对血小板进行形态学检查。透射电子显微镜技术复杂，由于需要昂贵的设备和训练有素的人员，其使用受到限制。在我们的研究中，我们使用 TEM 评估了 20 名健康捐献者血小板的形态参数。这项研究获得了德米特里-罗加乔夫国家小儿血液学、肿瘤学和免疫学医学研究中心独立伦理委员会和科学委员会的批准。
{"title":"A morphometric analysis of platelets using transmission electron microscopy","authors":"A. A. Kuznetsova, I. I. Kireev, S. Obydennyi","doi":"10.24287/1726-1708-2024-23-2-140-144","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-140-144","url":null,"abstract":"Platelets are the second most abundant human blood cells. They have an important function to form blood clots at sites of vascular injury to prevent bleeding. Abnormalities of platelet structure can lead to various dysfunctions and life-threatening situations. In some hereditary platelet disorders, morphological examination of platelets with transmission electron microscopy (TEM) may be required. TEM is technically complex, and its use is limited due to the need for expensive equipment and trained personnel. In our study, we assessed the morphometric parameters of platelets obtained from 20 healthy donors using TEM. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141816297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.24287/1726-1708-2024-23-2-145-151
D. S. Prudinnik, L. Koleva, E. Bovt, N. S. Kushnir, A. S. Suvorova, I. A. Dolgikh, S. S. Shakhidjanov, V. Vitvitsky, F. Ataullakhanov, E. Sinauridze, S. Plyasunova, N. S. Smetanina
The differential diagnosis of hereditary spherocytosis is a great challenge because of the similar clinical and laboratory signs it shares with other hereditary hemolytic anemias as well as due to the limited availability of molecular genetic testing. The development of easy-to-perform laboratory tests for the differential diagnosis of hereditary hemolytic anemias remains as relevant as ever. Here, a method of measuring red blood cell filterability for the diagnosis of hereditary spherocytosis is proposed for the first time. The aim of our study was to compare red blood cell filterability measurement with other diagnostic tests for hereditary spherocytosis as well as to assess its specificity and sensitivity. We included 30 patients (18 girls and 12 boys, with the median age of 8.6 years) with hereditary spherocytosis and 15 patients (9 girls and 6 boys, with the median age of 10 years) with other hereditary hemolytic anemias (pyruvate kinase deficiency (n = 14) and stomatocytosis (n = 1)). The diagnostic work-up for hereditary hemolytic anemia included a complete blood count test using an automated hematology analyzer, an osmotic resistance analysis before and after 24 hours of incubation at 37°С, erythrocytometry with sphericity index calculation, EMA test (eosin-5-maleimide binding assay) and red blood cell filterability measurement using artificial filters with cylindrical pores 3-5 μm in diameter. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The parents of all of the enrolled children signed a voluntary informed consent form for peripheral blood collection and diagnostic testing. In all the cases of hereditary spherocytosis diagnosed in accordance with the relevant clinical recommendations, red blood cell filterability was very low (0–0.31 units). It was higher only in 3 instances, reaching 0.47, 0.64 and 0.82 units, but in two of these cases there were no genetic data available, and the remaining patient was found to harbor the SPTA1 c.433999C>T mutation which was characterized both as spherocytosis and elliptocytosis. Red blood cell filterability in the group of the patients with other hemolytic anemias equalled 0.55 to 0.86 units (with the median of 0.77 units). The sensitivity of the RBC filterability measurement method in diagnosing hereditary spherocytosis was 93% (with 100% specificity), while the EMA test had a sensitivity of 89% and specificity of 95%. Our comparative study showed that red blood cell filterability measurement and the EMA test have similar sensitivity and specificity in diagnosing hereditary spherocytosis but the former is much cheaper and easier to perform since it does not require expensive equipment and can be carried out at any laboratory.
{"title":"Red blood cell filterability measurement in the diagnosis of hereditary spherocytosis","authors":"D. S. Prudinnik, L. Koleva, E. Bovt, N. S. Kushnir, A. S. Suvorova, I. A. Dolgikh, S. S. Shakhidjanov, V. Vitvitsky, F. Ataullakhanov, E. Sinauridze, S. Plyasunova, N. S. Smetanina","doi":"10.24287/1726-1708-2024-23-2-145-151","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-145-151","url":null,"abstract":"The differential diagnosis of hereditary spherocytosis is a great challenge because of the similar clinical and laboratory signs it shares with other hereditary hemolytic anemias as well as due to the limited availability of molecular genetic testing. The development of easy-to-perform laboratory tests for the differential diagnosis of hereditary hemolytic anemias remains as relevant as ever. Here, a method of measuring red blood cell filterability for the diagnosis of hereditary spherocytosis is proposed for the first time. The aim of our study was to compare red blood cell filterability measurement with other diagnostic tests for hereditary spherocytosis as well as to assess its specificity and sensitivity. We included 30 patients (18 girls and 12 boys, with the median age of 8.6 years) with hereditary spherocytosis and 15 patients (9 girls and 6 boys, with the median age of 10 years) with other hereditary hemolytic anemias (pyruvate kinase deficiency (n = 14) and stomatocytosis (n = 1)). The diagnostic work-up for hereditary hemolytic anemia included a complete blood count test using an automated hematology analyzer, an osmotic resistance analysis before and after 24 hours of incubation at 37°С, erythrocytometry with sphericity index calculation, EMA test (eosin-5-maleimide binding assay) and red blood cell filterability measurement using artificial filters with cylindrical pores 3-5 μm in diameter. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The parents of all of the enrolled children signed a voluntary informed consent form for peripheral blood collection and diagnostic testing. In all the cases of hereditary spherocytosis diagnosed in accordance with the relevant clinical recommendations, red blood cell filterability was very low (0–0.31 units). It was higher only in 3 instances, reaching 0.47, 0.64 and 0.82 units, but in two of these cases there were no genetic data available, and the remaining patient was found to harbor the SPTA1 c.433999C>T mutation which was characterized both as spherocytosis and elliptocytosis. Red blood cell filterability in the group of the patients with other hemolytic anemias equalled 0.55 to 0.86 units (with the median of 0.77 units). The sensitivity of the RBC filterability measurement method in diagnosing hereditary spherocytosis was 93% (with 100% specificity), while the EMA test had a sensitivity of 89% and specificity of 95%. Our comparative study showed that red blood cell filterability measurement and the EMA test have similar sensitivity and specificity in diagnosing hereditary spherocytosis but the former is much cheaper and easier to perform since it does not require expensive equipment and can be carried out at any laboratory.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"26 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141814387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.24287/1726-1708-2024-23-2-158-166
Y. Skvortsova
Chronic graft-versus-host disease (GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) caused by immune dysregulation leading to multisystem involvement resulting in tissue sclerosis. This is a long-term complication that can significantly affect the quality of life of HSCT recipients due to secondary immunodeficiency associated with combined immunosuppressive therapy, impaired organ function and even disability. In addition to active prophylaxis for chronic GVHD, regular follow-up of patients is necessary for early detection of signs and symptoms of GVHD to enable timely and effective treatment. Here, we present a brief overview of novel approaches to diagnosis, classification, and staging of chronic GVHD, as well as current prophylaxis and treatment options.
{"title":"Chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation","authors":"Y. Skvortsova","doi":"10.24287/1726-1708-2024-23-2-158-166","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-158-166","url":null,"abstract":"Chronic graft-versus-host disease (GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) caused by immune dysregulation leading to multisystem involvement resulting in tissue sclerosis. This is a long-term complication that can significantly affect the quality of life of HSCT recipients due to secondary immunodeficiency associated with combined immunosuppressive therapy, impaired organ function and even disability. In addition to active prophylaxis for chronic GVHD, regular follow-up of patients is necessary for early detection of signs and symptoms of GVHD to enable timely and effective treatment. Here, we present a brief overview of novel approaches to diagnosis, classification, and staging of chronic GVHD, as well as current prophylaxis and treatment options.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"16 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141814586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-21DOI: 10.24287/1726-1708-2024-23-2-107-115
A. O. Vereshchagina, G. Solopova, T. Bykova, M. Popova, D. N. Balashov, N. V. Suvorova, E. V. Rozanceva, P. A. Levin, L. Zubarovskaya, G. Novichkova
The clinical course of the novel coronavirus disease (COVID-19) in patients with oncological and hematological diseases after hematopoietic stem cell transplantation (HSCT), are of special interest. To further investigate the problem, a two-center study was undertaken at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the R.M. Gorbacheva National Research Institute for Pediatric Oncology, Hematology and Transplantation between January 2020 and January 2023. This was a retrospective-prospective, non-randomized, non-interventional study that included children aged 0–19 years with oncological and hematological diseases and primary immunodeficiencies who had undergone allogeneic HSCT and subsequently contracted COVID-19. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. COVID-19 cases were confirmed by polymerase chain reaction testing and classified as asymptomatic, mild, moderate, severe, and critical. The study included 105 patients with a median age of 9 years; male patients were predominant (the male-to-female ratio was 1.8:1). The primary diseases were hematological malignancies (73%), benign hematological diseases (14%) and primary immunodeficiencies (13%). The most common clinical symptoms of COVID-19 were fever, gastrointestinal symptoms, and respiratory symptoms; 40% of COVID-19 cases were asymptomatic. Lymphopenia was found to be a risk factor for severe COVID-19. The patients without immune reconstitution had a longer persistence of the COVID-19 virus than those with immune reconstitution (17 days versus 13 days), however, no significant differences were obtained (p = 0.7). There were also no significant differences in the severity and outcomes of COVID-19 between the patients with immune reconstitution and those without reconstitution. There was no effect of therapy on the duration of COVID-19, and there was no association between the type of treatment and the duration of the disease. The overall survival rate in the allo-HSCT recipients who had been diagnosed with COVID-19 was 88%, which was lower than in the non-recipients (88% vs 94%; p = 0,077).
{"title":"The clinical course of the novel coronavirus disease in children after allogeneic hematopoietic stem cell transplantation","authors":"A. O. Vereshchagina, G. Solopova, T. Bykova, M. Popova, D. N. Balashov, N. V. Suvorova, E. V. Rozanceva, P. A. Levin, L. Zubarovskaya, G. Novichkova","doi":"10.24287/1726-1708-2024-23-2-107-115","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-107-115","url":null,"abstract":"The clinical course of the novel coronavirus disease (COVID-19) in patients with oncological and hematological diseases after hematopoietic stem cell transplantation (HSCT), are of special interest. To further investigate the problem, a two-center study was undertaken at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the R.M. Gorbacheva National Research Institute for Pediatric Oncology, Hematology and Transplantation between January 2020 and January 2023. This was a retrospective-prospective, non-randomized, non-interventional study that included children aged 0–19 years with oncological and hematological diseases and primary immunodeficiencies who had undergone allogeneic HSCT and subsequently contracted COVID-19. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. COVID-19 cases were confirmed by polymerase chain reaction testing and classified as asymptomatic, mild, moderate, severe, and critical. The study included 105 patients with a median age of 9 years; male patients were predominant (the male-to-female ratio was 1.8:1). The primary diseases were hematological malignancies (73%), benign hematological diseases (14%) and primary immunodeficiencies (13%). The most common clinical symptoms of COVID-19 were fever, gastrointestinal symptoms, and respiratory symptoms; 40% of COVID-19 cases were asymptomatic. Lymphopenia was found to be a risk factor for severe COVID-19. The patients without immune reconstitution had a longer persistence of the COVID-19 virus than those with immune reconstitution (17 days versus 13 days), however, no significant differences were obtained (p = 0.7). There were also no significant differences in the severity and outcomes of COVID-19 between the patients with immune reconstitution and those without reconstitution. There was no effect of therapy on the duration of COVID-19, and there was no association between the type of treatment and the duration of the disease. The overall survival rate in the allo-HSCT recipients who had been diagnosed with COVID-19 was 88%, which was lower than in the non-recipients (88% vs 94%; p = 0,077).","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"90 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141818723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-21DOI: 10.24287/1726-1708-2024-23-2-116-127
T. Z. Aliev, K. Kirgizov, E. Machneva, I. Kostareva, K. Sergeenko, D. S. Smirnova, N. Burlaka, Yu. V. Lozovan, I. Y. Trushkova, A. Elfimova, K. V. Mitrakov, T. I. Potemkina, M. D. Malova, R. R. Fatkhullin, N. Stepanyan, D. A. Kapkova, G. Sagoyan, A. M. Suleymanova, N. Matinyan, G. Muftakhova, A. P. Kazantsev, O. M. Romantsova, M. Rubanskaya, T. Ushakova, A. Rodina, V. V. Zhogov, V. S. Vanesyan, Y. Skvortsova, I. Kazantsev, A. S. Slinin, T. Gorbunova, T. T. Valiev, V. G. Polyakov, S. Varfolomeeva
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
{"title":"Complications of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation in children with solid malignant neoplasms: a single-center experience","authors":"T. Z. Aliev, K. Kirgizov, E. Machneva, I. Kostareva, K. Sergeenko, D. S. Smirnova, N. Burlaka, Yu. V. Lozovan, I. Y. Trushkova, A. Elfimova, K. V. Mitrakov, T. I. Potemkina, M. D. Malova, R. R. Fatkhullin, N. Stepanyan, D. A. Kapkova, G. Sagoyan, A. M. Suleymanova, N. Matinyan, G. Muftakhova, A. P. Kazantsev, O. M. Romantsova, M. Rubanskaya, T. Ushakova, A. Rodina, V. V. Zhogov, V. S. Vanesyan, Y. Skvortsova, I. Kazantsev, A. S. Slinin, T. Gorbunova, T. T. Valiev, V. G. Polyakov, S. Varfolomeeva","doi":"10.24287/1726-1708-2024-23-2-116-127","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-2-116-127","url":null,"abstract":"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","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141818593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.24287/1726-1708-2024-23-1-211-218
A. N. Sveshnikova, E. A. Adamanskaya, M. A. Panteleev
The formation of DNA extracellular traps of neutrophils (NET-osis) is a mechanism of programmed cell death of leukocytes, which initially has antibacterial and antifungal functions. The ability of neutrophils to become activated upon contact with activated platelets and, in turn, to activate the contact coagulation pathway via DNA traps plays a central role in venous thrombosis and disseminated intravascular coagulation in COVID-19. At the same time, the intracellular signaling that controls NET-osis is extremely poorly understood even for the simplest cases, when this process is caused by lipopolysaccharides of the bacterial cell wall. In this review, we consider the case of NET-osis in thrombosis, for which there are even more questions. We focused on the conditions for NET-osis observation and features in different scenarios.
中性粒细胞 DNA 细胞外陷阱（NET-osis）的形成是白细胞程序性细胞死亡的一种机制，最初具有抗菌和抗真菌功能。中性粒细胞与活化血小板接触后会被激活，进而通过 DNA 陷阱激活接触性凝血途径，这在 COVID-19 静脉血栓形成和弥散性血管内凝血中起着核心作用。与此同时，人们对控制 NET-osis 的细胞内信号传导知之甚少，即使是最简单的由细菌细胞壁脂多糖引起的情况也是如此。在这篇综述中，我们探讨了血栓形成过程中的 NET-osis 情况，对此存在更多疑问。我们重点讨论了观察 NET-osis 的条件和不同情况下的特征。
{"title":"Conditions for the implementation of the phenomenon of programmed death of neutrophils with the appearance of DNA extracellular traps during thrombus formation","authors":"A. N. Sveshnikova, E. A. Adamanskaya, M. A. Panteleev","doi":"10.24287/1726-1708-2024-23-1-211-218","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-211-218","url":null,"abstract":" The formation of DNA extracellular traps of neutrophils (NET-osis) is a mechanism of programmed cell death of leukocytes, which initially has antibacterial and antifungal functions. The ability of neutrophils to become activated upon contact with activated platelets and, in turn, to activate the contact coagulation pathway via DNA traps plays a central role in venous thrombosis and disseminated intravascular coagulation in COVID-19. At the same time, the intracellular signaling that controls NET-osis is extremely poorly understood even for the simplest cases, when this process is caused by lipopolysaccharides of the bacterial cell wall. In this review, we consider the case of NET-osis in thrombosis, for which there are even more questions. We focused on the conditions for NET-osis observation and features in different scenarios.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140683892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.24287/1726-1708-2024-23-1-219-230
I. A. Demina, E. Mikhailova, A. Semchenkova, T. Verzhbitskaya, Zh. V. Permikin, S. Kashpor, E. Zerkalenkova, G. Tsaur, Y. Olshanskaya, L. Fechina, A. Karachunskiy, G. Novichkova, A. Popov
Acute leukemias of ambiguous lineage (ALAL) are rare acute leukemias (AL) that exhibit specific features of more than one hematopoietic lineage or show no distinct evidence of lineage differentiation. Immunophenotyping plays a key role in the diagnosis and classification of ALAL. Despite the availability of diagnostic criteria for ALAL proposed by different expert groups, the accurate diagnosis of ALAL representing a rare and heterogeneous group of diseases remains a challenge. In this paper, we present a brief analysis of 97 pediatric ALAL cases. Such a large cohort of cases with ALAL (ALALs comprising less than 1 % of all pediatric AL) was obtained as a result of the centralized diagnosis of AL. With regard to the obtained results, we have developed the guidelines for the interpretation of the results of immunophenotyping in the diagnosis of ALAL and for the integration of findings from flow cytometry, cytomorphology and genetic testing for the accurate diagnosis and classification of this group of AL.
血系不清的急性白血病（ALAL）是一种罕见的急性白血病（AL），表现出一种以上造血血系的特异性特征，或没有明显的血系分化证据。免疫分型在 ALAL 的诊断和分类中起着关键作用。尽管不同的专家组提出了 ALAL 的诊断标准，但如何准确诊断 ALAL 这一罕见的异质性疾病仍是一项挑战。本文简要分析了 97 例小儿 ALAL 病例。如此庞大的 ALAL 病例群（ALAL 病例不到所有小儿 ALAL 病例的 1%）是 AL 集中诊断的结果。根据所获得的结果，我们制定了在诊断 ALAL 时解释免疫分型结果的指南，以及整合流式细胞术、细胞形态学和基因检测结果以准确诊断和分类这类 ALAL 的指南。
{"title":"Immunophenotyping in the diagnosis of acute leukemias of ambiguous lineage. The results of centralized diagnosis and practical guidelines","authors":"I. A. Demina, E. Mikhailova, A. Semchenkova, T. Verzhbitskaya, Zh. V. Permikin, S. Kashpor, E. Zerkalenkova, G. Tsaur, Y. Olshanskaya, L. Fechina, A. Karachunskiy, G. Novichkova, A. Popov","doi":"10.24287/1726-1708-2024-23-1-219-230","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-219-230","url":null,"abstract":" Acute leukemias of ambiguous lineage (ALAL) are rare acute leukemias (AL) that exhibit specific features of more than one hematopoietic lineage or show no distinct evidence of lineage differentiation. Immunophenotyping plays a key role in the diagnosis and classification of ALAL. Despite the availability of diagnostic criteria for ALAL proposed by different expert groups, the accurate diagnosis of ALAL representing a rare and heterogeneous group of diseases remains a challenge. In this paper, we present a brief analysis of 97 pediatric ALAL cases. Such a large cohort of cases with ALAL (ALALs comprising less than 1 % of all pediatric AL) was obtained as a result of the centralized diagnosis of AL. With regard to the obtained results, we have developed the guidelines for the interpretation of the results of immunophenotyping in the diagnosis of ALAL and for the integration of findings from flow cytometry, cytomorphology and genetic testing for the accurate diagnosis and classification of this group of AL.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" January","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140682931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：