Pub Date : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-62-72
L. A. Vavilova, Y. Y. Dyakonova, O. Bydanov, N. Myakova, Y. Abugova, L. K. Anderzhanova, D. Evstratov, E. Kurnikova, A. Popov, Y. Olshanskaya, M. Maschan, L. Shelikhova, D. Litvinov, A. Popa, A. Karachunskiy
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite remarkable improvements in the treatment of pediatric acute lymphoblastic leukemia over last years, relapse still carries a poor prognosis with considerable morbidity and mortality. New immunotherapeutic approaches will change the way we treated our patients and the results we had. Blinatumomab is a bispecific T-cell-engaging antibody indicated for the treatment of relapsed/refractory B-cell lymphoblastic leukemia. The use of Blinatumomab in relapsed B-cell ALL has shown promising effects, especially as a bridging tool to hematopoietic stem cell transplantation. The therapy results for patients in the high risk group remain far from optimal due to refractoriness to chemotherapy, death from infectious complications, as well as acute chemotherapy toxicity. This article demonstrates the results of our experience of using Blinatumomab in children with the high-risk group relapsed B-cell ALL treated according to the ALL-REZ 2016 protocol. 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 efficacy and toxicity of innovational blocks with the use of fludarabine and clofarabine with subsequent Blinatumomab infusion are shown. And we present the efficacy of autologous CD3+ lymphocytes infusion once a week during the continuous blinatumomab therapy. Also we demonstrate the results of using Blinatumomab for the treatment of patients with refractory to the first line therapy relapsed B-lymphoblastic leukemia and patients with a second relapse of B-cell ALL. The first line therapy in these patients was carried out according to the ALL-REZ 2014 protocol. Our results show an improved reduction in minimal residual disease in patients with refractory relapsed B-cell ALL as well as an increased event free survival in children with the high-risk group relapsed B-cell ALL.
{"title":"The role of blinatumomab in the treatment of B-cell relapses of acute lymphoblastic leukemia in children: own experience","authors":"L. A. Vavilova, Y. Y. Dyakonova, O. Bydanov, N. Myakova, Y. Abugova, L. K. Anderzhanova, D. Evstratov, E. Kurnikova, A. Popov, Y. Olshanskaya, M. Maschan, L. Shelikhova, D. Litvinov, A. Popa, A. Karachunskiy","doi":"10.24287/1726-1708-2023-22-1-62-72","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-62-72","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite remarkable improvements in the treatment of pediatric acute lymphoblastic leukemia over last years, relapse still carries a poor prognosis with considerable morbidity and mortality. New immunotherapeutic approaches will change the way we treated our patients and the results we had. Blinatumomab is a bispecific T-cell-engaging antibody indicated for the treatment of relapsed/refractory B-cell lymphoblastic leukemia. The use of Blinatumomab in relapsed B-cell ALL has shown promising effects, especially as a bridging tool to hematopoietic stem cell transplantation. The therapy results for patients in the high risk group remain far from optimal due to refractoriness to chemotherapy, death from infectious complications, as well as acute chemotherapy toxicity. This article demonstrates the results of our experience of using Blinatumomab in children with the high-risk group relapsed B-cell ALL treated according to the ALL-REZ 2016 protocol. 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 efficacy and toxicity of innovational blocks with the use of fludarabine and clofarabine with subsequent Blinatumomab infusion are shown. And we present the efficacy of autologous CD3+ lymphocytes infusion once a week during the continuous blinatumomab therapy. Also we demonstrate the results of using Blinatumomab for the treatment of patients with refractory to the first line therapy relapsed B-lymphoblastic leukemia and patients with a second relapse of B-cell ALL. The first line therapy in these patients was carried out according to the ALL-REZ 2014 protocol. Our results show an improved reduction in minimal residual disease in patients with refractory relapsed B-cell ALL as well as an increased event free survival in children with the high-risk group relapsed B-cell ALL.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81195296","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-12-20
D. Osipova, E. Raykina, E. Lyudovskikh, D. Evseev, I. Kalinina, D. D. Baydildina, A. Popov, A. Semchenkova, E. A. Burtsev, G. Bronin, A. Maschan, M. Maschan
This article discusses the potential of droplet digital polymerase chain reaction (PCR) for the diagnostic detection and monitoring of the allelic load of the BRAF V600E mutation in circulating cell-free DNA and myeloid progenitor cell population in the bone marrow of patients with Langerhans cell histiocytosis (LCH). Droplet digital PCR may serve as a useful tool for the monitoring of minimal residual disease and improve our understanding of the pathogenesis of Langerhans cells histiocytosis. 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.
{"title":"The use of droplet digital polymerase chain reaction for the molecular diagnosis and monitoring of treatment response in patients with Langerhans cell histiocytosis with the BRAF V600E mutation","authors":"D. Osipova, E. Raykina, E. Lyudovskikh, D. Evseev, I. Kalinina, D. D. Baydildina, A. Popov, A. Semchenkova, E. A. Burtsev, G. Bronin, A. Maschan, M. Maschan","doi":"10.24287/1726-1708-2023-22-1-12-20","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-12-20","url":null,"abstract":"This article discusses the potential of droplet digital polymerase chain reaction (PCR) for the diagnostic detection and monitoring of the allelic load of the BRAF V600E mutation in circulating cell-free DNA and myeloid progenitor cell population in the bone marrow of patients with Langerhans cell histiocytosis (LCH). Droplet digital PCR may serve as a useful tool for the monitoring of minimal residual disease and improve our understanding of the pathogenesis of Langerhans cells histiocytosis. 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":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84567645","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-78-83
P. Zharkov, D. B. Florinskiy, O. Aleynikova, G. A. Novichkovа
Rare bleeding disorders account for about 3–5% of all inherited bleeding disorders. Due to the rarity and complexity of diagnosing these disorders, their prevalence estimates vary greatly. There is currently no national registry of rare inherited bleeding disorders and their prevalence across the country has not been studied yet. Aim: to estimate the prevalence of rare coagulation disorders among Russian children. For this multicenter study, we used retrospective anonymous patient data collected during clinical practice, so the approval of the ethics committee was not required. We analyzed completed questionnaires containing the number of patients with rare bleeding disorders aged from 0 to 18 years from 72 subjects of the Russian Federation. The survey had been conducted from April to June 2022. Our analysis included patients with deficiencies of factor I, II, V, VII, X, XI or XIII, as well as with combined factor deficiencies and unspecified hemorrhagic conditions. According to the reported data, the total number of children with rare bleeding disorders is 398. The most common disorder is deficiency of factor VII (52%, n = 210); it is followed by fibrinogen deficiency (16%, n = 63) and deficiency of factor X (12%, n = 48). Deficiencies of factors XI, V and XIII account for 9% (n = 35), 5% (n = 20), and 4.5% (n = 18) of all cases, respectively. Combined factor deficiency was diagnosed in 1.7% of patients (n = 7) and factor II deficiency was detected in only 1% of patients (n = 4). In order to determine the actual prevalence and incidence of rare coagulation disorders and their clinical manifestations and to identify the need for factor concentrates, it is necessary to establish a national registry of rare bleeding disorders, following the example of the national hemophilia registry.
{"title":"The prevalence of rare bleeding disorders among children in the Russian Federation","authors":"P. Zharkov, D. B. Florinskiy, O. Aleynikova, G. A. Novichkovа","doi":"10.24287/1726-1708-2023-22-1-78-83","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-78-83","url":null,"abstract":"Rare bleeding disorders account for about 3–5% of all inherited bleeding disorders. Due to the rarity and complexity of diagnosing these disorders, their prevalence estimates vary greatly. There is currently no national registry of rare inherited bleeding disorders and their prevalence across the country has not been studied yet. Aim: to estimate the prevalence of rare coagulation disorders among Russian children. For this multicenter study, we used retrospective anonymous patient data collected during clinical practice, so the approval of the ethics committee was not required. We analyzed completed questionnaires containing the number of patients with rare bleeding disorders aged from 0 to 18 years from 72 subjects of the Russian Federation. The survey had been conducted from April to June 2022. Our analysis included patients with deficiencies of factor I, II, V, VII, X, XI or XIII, as well as with combined factor deficiencies and unspecified hemorrhagic conditions. According to the reported data, the total number of children with rare bleeding disorders is 398. The most common disorder is deficiency of factor VII (52%, n = 210); it is followed by fibrinogen deficiency (16%, n = 63) and deficiency of factor X (12%, n = 48). Deficiencies of factors XI, V and XIII account for 9% (n = 35), 5% (n = 20), and 4.5% (n = 18) of all cases, respectively. Combined factor deficiency was diagnosed in 1.7% of patients (n = 7) and factor II deficiency was detected in only 1% of patients (n = 4). In order to determine the actual prevalence and incidence of rare coagulation disorders and their clinical manifestations and to identify the need for factor concentrates, it is necessary to establish a national registry of rare bleeding disorders, following the example of the national hemophilia registry.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"PC-22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84839051","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-122-125
E. Lyudovskikh, D. Evseev, D. Osipova, E. Raykina, I. Kalinina, D. Baidildina, A. Maschan, M. Maschan
Here we report a clinical case of a patient with BRAF-positive Langerhans cell histiocytosis treated with combination therapy including trametinib. As the patient was undergoing long-term therapy with a BRAF inhibitor, his underlying disease reactivated. Hence it was suggested that the child might have become resistant to the treatment as a result of a subclonal mutation. It was concluded that this event undermined the efficacy of long-term therapy with BRAF inhibitors and highlighted the need for further study of possible molecular genetic mechanisms involved in the pathogenesis of Langerhans cell histiocytosis, as well as the need for the development of new treatment approaches. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.
{"title":"Resistance to BRAF inhibitors in a patient with BRAF V600E-positive Langerhans cell histiocytosis","authors":"E. Lyudovskikh, D. Evseev, D. Osipova, E. Raykina, I. Kalinina, D. Baidildina, A. Maschan, M. Maschan","doi":"10.24287/1726-1708-2023-22-1-122-125","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-122-125","url":null,"abstract":"Here we report a clinical case of a patient with BRAF-positive Langerhans cell histiocytosis treated with combination therapy including trametinib. As the patient was undergoing long-term therapy with a BRAF inhibitor, his underlying disease reactivated. Hence it was suggested that the child might have become resistant to the treatment as a result of a subclonal mutation. It was concluded that this event undermined the efficacy of long-term therapy with BRAF inhibitors and highlighted the need for further study of possible molecular genetic mechanisms involved in the pathogenesis of Langerhans cell histiocytosis, as well as the need for the development of new treatment approaches. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91109234","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-73-77
N. Kriventsova, G. Tereshchenko
Aplastic anemia is a life-threatening condition characterized by the suppression of all hematopoietic lineages in the bone marrow. Empty intertrabecular spaces are replaced by adipose tissue. With modern MR techniques for assessing fat fraction, it has become possible to capture these changes. The fat fraction is estimated as the ratio of the signal intensity from fat to the sum of the fat and water signals. Aim of the study: to assess the diagnostic value of bone marrow fat fraction quantification in patients aged < 18 years with aplastic anemia. 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 of the Ministry of Healthcare of the Russian Federation. The study included 66 participants aged under 18 years. A control group consisted of 33 healthy subjects with a mean age of 13.03 ± 2.83 years. A group of interest included 33 children with a confirmed diagnosis of aplastic anemia, with a mean age of 12.31 ± 4.39 years. The study was carried out at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Healthcare of the Russian Federation; all scanning was performed on a Philips Achieva 3.0T MRI scanner using the mDixon-quant sequence in the iliac bones and lumbar vertebrae. Our results showed that bone marrow fat fraction was significantly higher in the aplastic anemia group than in the controls. In the patients with aplastic anemia, the mean fat fraction values in the iliac bones and in the L4, L5 vertebrae were 82.62 ± 10.92% and 73.52 ± 17.52%, respectively. In the control group, the mean fat fraction values for these sites were 51.04 ± 11.41% and 31.43 ± 10.61%, respectively. We found a significant difference in fat fraction values for the same sites between the groups (p < 0.01). Bone marrow fat fraction quantification by MRI allows for the detection of decreased cellularity of the marrow in patients under 18 years of age with aplastic anemia compared to healthy children.
{"title":"Bone marrow cellularity assessment using magnetic resonance imaging in children with aplastic anemia","authors":"N. Kriventsova, G. Tereshchenko","doi":"10.24287/1726-1708-2023-22-1-73-77","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-73-77","url":null,"abstract":"Aplastic anemia is a life-threatening condition characterized by the suppression of all hematopoietic lineages in the bone marrow. Empty intertrabecular spaces are replaced by adipose tissue. With modern MR techniques for assessing fat fraction, it has become possible to capture these changes. The fat fraction is estimated as the ratio of the signal intensity from fat to the sum of the fat and water signals. Aim of the study: to assess the diagnostic value of bone marrow fat fraction quantification in patients aged < 18 years with aplastic anemia. 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 of the Ministry of Healthcare of the Russian Federation. The study included 66 participants aged under 18 years. A control group consisted of 33 healthy subjects with a mean age of 13.03 ± 2.83 years. A group of interest included 33 children with a confirmed diagnosis of aplastic anemia, with a mean age of 12.31 ± 4.39 years. The study was carried out at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Healthcare of the Russian Federation; all scanning was performed on a Philips Achieva 3.0T MRI scanner using the mDixon-quant sequence in the iliac bones and lumbar vertebrae. Our results showed that bone marrow fat fraction was significantly higher in the aplastic anemia group than in the controls. In the patients with aplastic anemia, the mean fat fraction values in the iliac bones and in the L4, L5 vertebrae were 82.62 ± 10.92% and 73.52 ± 17.52%, respectively. In the control group, the mean fat fraction values for these sites were 51.04 ± 11.41% and 31.43 ± 10.61%, respectively. We found a significant difference in fat fraction values for the same sites between the groups (p < 0.01). Bone marrow fat fraction quantification by MRI allows for the detection of decreased cellularity of the marrow in patients under 18 years of age with aplastic anemia compared to healthy children.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75107093","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-32-38
E. Volchkov, Y. Abugova, I. Mamedov, D. Abramov, M. Senchenko, L. K. Anderzhanova, A. Komkov, V. Fominykh, Y. Olshanskaya, N. Myakova, G. Novichkova
The effectiveness of treatment for children with B-cell non-Hodgkin lymphomas (B-NHL) has reached 85–90% after the introduction of modern risk-adapted treatment regimens that involve risk group stratification based on tumor stage. Bone marrow involvement is traditionally evaluated using quantitative morphological analysis of tumor cells which has, however, a lower sensitivity compared to molecular genetic methods. In our study, we used next generation sequencing (NGS) to identify tumor-specific V-(D)/J-rearrangements of immunoglobulin genes which can be used as a marker for the evaluation of minimal disseminated disease (MDD) in children with B-NHL. 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. Here we demonstrated that NGS allows detection of bone marrow involvement at a sensitivity of 10–6 in patients with Burkitt lymphoma, in whom standard morphological analysis failed to reveal the presence of tumor cells. The detection of molecular MDD can improve tumor staging and risk stratification in children with B-cell non-Hodgkin lymphomas.
{"title":"The evaluation of minimal disseminated disease in the bone marrow of children with Burkitt lymphoma using next generation sequencing","authors":"E. Volchkov, Y. Abugova, I. Mamedov, D. Abramov, M. Senchenko, L. K. Anderzhanova, A. Komkov, V. Fominykh, Y. Olshanskaya, N. Myakova, G. Novichkova","doi":"10.24287/1726-1708-2023-22-1-32-38","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-32-38","url":null,"abstract":"The effectiveness of treatment for children with B-cell non-Hodgkin lymphomas (B-NHL) has reached 85–90% after the introduction of modern risk-adapted treatment regimens that involve risk group stratification based on tumor stage. Bone marrow involvement is traditionally evaluated using quantitative morphological analysis of tumor cells which has, however, a lower sensitivity compared to molecular genetic methods. In our study, we used next generation sequencing (NGS) to identify tumor-specific V-(D)/J-rearrangements of immunoglobulin genes which can be used as a marker for the evaluation of minimal disseminated disease (MDD) in children with B-NHL. 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. Here we demonstrated that NGS allows detection of bone marrow involvement at a sensitivity of 10–6 in patients with Burkitt lymphoma, in whom standard morphological analysis failed to reveal the presence of tumor cells. The detection of molecular MDD can improve tumor staging and risk stratification in children with B-cell non-Hodgkin lymphomas.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"227 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74467915","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-165-177
A. Popov, T. Verzhbitskaya, L. Movchan, I. A. Demina, E. Mikhailova, A. Semchenkova, Zh. V. Permikin, T. Shman, A. Karachunskiy, G. Novichkova
Flow cytometry is one of the key technologies for acute leukemia (AL) diagnostics. Nevertheless, lack of technological standards hampers implementation of immunophenotyping data in treatment protocols. Earlier our group published the acute lymphoblastic leukemia diagnostic standards. In this paper, we present the updated guidelines for initial immunophenotyping of ALs. This wellharmonized approach includes recommendations for monoclonal antibodies choice, sample preparation, cytometer setup, data analysis and interpretation as well as for the report writing. These guidelines allows application of diagnostic flow cytometric studies in all types of AL.
{"title":"Flow cytometry in acute leukemia diagnostics. Guidelines of Russian-Belarusian multicenter group for pediatric leukemia studies","authors":"A. Popov, T. Verzhbitskaya, L. Movchan, I. A. Demina, E. Mikhailova, A. Semchenkova, Zh. V. Permikin, T. Shman, A. Karachunskiy, G. Novichkova","doi":"10.24287/1726-1708-2023-22-1-165-177","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-165-177","url":null,"abstract":"Flow cytometry is one of the key technologies for acute leukemia (AL) diagnostics. Nevertheless, lack of technological standards hampers implementation of immunophenotyping data in treatment protocols. Earlier our group published the acute lymphoblastic leukemia diagnostic standards. In this paper, we present the updated guidelines for initial immunophenotyping of ALs. This wellharmonized approach includes recommendations for monoclonal antibodies choice, sample preparation, cytometer setup, data analysis and interpretation as well as for the report writing. These guidelines allows application of diagnostic flow cytometric studies in all types of AL.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82647965","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-22-31
A. N. Galimov, E. Lepik, A. Kozlov, A. G. Gevorgian, I. Kazantsev, T. Yukhta, V. Baikov, A. Shvetsov, I. Nikolaev, P. Tolkunova, N. Mikhaylova, K. Lepik, Y. Punanov, A. Kulagin, L. Zubarovskaya
Anaplastic large cell lymphoma (ALCL) expressing the anaplastic lymphoma kinase (ALK) (ALK+ ALCL) is a rare type of lymphoma which comprises 10-15% of all non-Hodgkin lymphomas in children and 2–3% in young adults. Relapsed/refractory disease occurs even more rarely (25–40% of all cases). There is as yet no standard treatment for relapsed/refractory ALK+ ALCL. Patients with ALK+ ALCL usually present at advanced stages of the disease with extranodal involvement (skin, soft tissues, bones, lungs, liver, spleen and bone marrow) and B symptoms. ALK-positive ALCL affects males more often than females. There are two morphological variants: the common type (65% of cases) and the non-common type which is associated with a poorer prognosis. ALK+ ALCLs are often associated with t(2;5) and t(1;2), resulting in the formation of the NPM-ALK and the TPM3-ALK fusion proteins, respectively. Data about the treatment of relapsed/refractory ALK+ ALCL are limited. Earlier, targeted therapies (brentuximab vedotin (BV), ALK inhibitors) and risk-adapted chemotherapy followed by hematopoietic stem cell transplantation (HSCT) for remission consolidation were shown to be highly effective. A total of 15 patients with relapsed/refractory ALK+ ALCL were treated at the R.M. Gorbacheva Research Institute starting from 2002. Fourteen (93%) patients had ALK-positive ALCL of common morphology and one (7%) patient had the non-common variant (histiocytic). The study was approved by the Independent Ethics Committee and the Scientific Council of the Pavlov University. The expression of CD3 on tumor cells was assessed (CD3 positive: n = 4 (27%), CD3 negative: n = 8 (53%), no data: n = 3 (20%). The median age at the diagnosis was 26 years (11 months– 37 years). The median follow-up from the diagnosis was 9 years (1–19 years). Nine (60%) patients were aged > 18 years and six (40%) patients were aged < 18 years. There were 10 (67%) males and 5 (33%) females. At onset, 2 (13%) patients were diagnosed with early-stage disease (stage II), while the others were diagnosed with advanced-stage disease: 2 (13%) patients had stage III disease and 11 (74%) had stage IV disease. Staging was performed according to the St. Jude staging system (in children) and the Ann Arbour staging classification (in adults). Thirteen (86%) patients had extranodal involvement. Four (27%) patients had refractory disease (progression within the first three months or the absence of complete remission after the first-line treatment) and the rest 11 (73%) patients had recurrent ALK-positive ALCL. Six patients developed early relapse (< 12 months after remission was achieved); 5 patients had late relapse (after > 12 months of remission); local (1 site) and systemic relapses were diagnosed in 7 and 4 patients, respectively. Our patients received from 2 to 7 lines of treatment (the median is 4). In the first line of therapy, the patients were treated according to NHL-BFM based regimens (n = 9; 60%), the CHOP (n = 5; 33%), a
{"title":"The treatment of relapsed/refractory anaplastic large cell lymphoma expressing the anaplastic lymphoma kinase: a single-center experience","authors":"A. N. Galimov, E. Lepik, A. Kozlov, A. G. Gevorgian, I. Kazantsev, T. Yukhta, V. Baikov, A. Shvetsov, I. Nikolaev, P. Tolkunova, N. Mikhaylova, K. Lepik, Y. Punanov, A. Kulagin, L. Zubarovskaya","doi":"10.24287/1726-1708-2023-22-1-22-31","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-22-31","url":null,"abstract":"Anaplastic large cell lymphoma (ALCL) expressing the anaplastic lymphoma kinase (ALK) (ALK+ ALCL) is a rare type of lymphoma which comprises 10-15% of all non-Hodgkin lymphomas in children and 2–3% in young adults. Relapsed/refractory disease occurs even more rarely (25–40% of all cases). There is as yet no standard treatment for relapsed/refractory ALK+ ALCL. Patients with ALK+ ALCL usually present at advanced stages of the disease with extranodal involvement (skin, soft tissues, bones, lungs, liver, spleen and bone marrow) and B symptoms. ALK-positive ALCL affects males more often than females. There are two morphological variants: the common type (65% of cases) and the non-common type which is associated with a poorer prognosis. ALK+ ALCLs are often associated with t(2;5) and t(1;2), resulting in the formation of the NPM-ALK and the TPM3-ALK fusion proteins, respectively. Data about the treatment of relapsed/refractory ALK+ ALCL are limited. Earlier, targeted therapies (brentuximab vedotin (BV), ALK inhibitors) and risk-adapted chemotherapy followed by hematopoietic stem cell transplantation (HSCT) for remission consolidation were shown to be highly effective. A total of 15 patients with relapsed/refractory ALK+ ALCL were treated at the R.M. Gorbacheva Research Institute starting from 2002. Fourteen (93%) patients had ALK-positive ALCL of common morphology and one (7%) patient had the non-common variant (histiocytic). The study was approved by the Independent Ethics Committee and the Scientific Council of the Pavlov University. The expression of CD3 on tumor cells was assessed (CD3 positive: n = 4 (27%), CD3 negative: n = 8 (53%), no data: n = 3 (20%). The median age at the diagnosis was 26 years (11 months– 37 years). The median follow-up from the diagnosis was 9 years (1–19 years). Nine (60%) patients were aged > 18 years and six (40%) patients were aged < 18 years. There were 10 (67%) males and 5 (33%) females. At onset, 2 (13%) patients were diagnosed with early-stage disease (stage II), while the others were diagnosed with advanced-stage disease: 2 (13%) patients had stage III disease and 11 (74%) had stage IV disease. Staging was performed according to the St. Jude staging system (in children) and the Ann Arbour staging classification (in adults). Thirteen (86%) patients had extranodal involvement. Four (27%) patients had refractory disease (progression within the first three months or the absence of complete remission after the first-line treatment) and the rest 11 (73%) patients had recurrent ALK-positive ALCL. Six patients developed early relapse (< 12 months after remission was achieved); 5 patients had late relapse (after > 12 months of remission); local (1 site) and systemic relapses were diagnosed in 7 and 4 patients, respectively. Our patients received from 2 to 7 lines of treatment (the median is 4). In the first line of therapy, the patients were treated according to NHL-BFM based regimens (n = 9; 60%), the CHOP (n = 5; 33%), a","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84119355","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-110-121
G. Movsisyan, A. D. Komarova, K. Kulikov, I. Kalinina, M. Lokhmatov, V. Oldakovskiy, R. Tepaev, E. Roslavtseva, A. Potapov, N. Shchigoleva, A. I. Materikin, K. Savostyanov
Exudative enteropathy is a clinical syndrome characterized by excessive loss of proteins through the gastrointestinal tract and is a rare complication of various gastrointestinal diseases. One of the rarest causes of protein malabsorption is Langerhans cell histiocytosis, which occurs as a result of inflammatory neoplasia of myeloid precursor cells caused by mutations in the mitogenactivated protein kinase pathway. Abnormal proliferation and accumulation of Langerhans cells in the intestinal wall leads to a violation of the outflow of lymph, and causes clinical manifestations characteristic of enteropathy. Given that the lesion of the gastrointestinal tract with histiocytosis from Langerhans cells occurs in 2–3% of cases, and the clinical signs are not highly specific, timely diagnosis is difficult. Delayed verification of the diagnosis and late initiation of adequate treatment are risk factors for multisystem lesions and lead to an unfavorable outcome. The literature describes a few observations of the onset or manifestation of the disease with symptoms of protein malabsorption. We present a rare clinical case of diagnosing histiocytosis from Langerhans cells in a young child with severe manifestations of exudative enteropathy at the onset. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.Refractory gastrointestinal symptoms require mandatory endoscopic and histological examination to identify rare causes of malabsorption. Timely initiation of targeted therapy with vemurafenib in combination with subsequent chemotherapy provided the child with a favorable prognosis and stable remission of the disease.
{"title":"Langerhans cell histiocytosis: a rare cause of exudative enteropathy in a young child","authors":"G. Movsisyan, A. D. Komarova, K. Kulikov, I. Kalinina, M. Lokhmatov, V. Oldakovskiy, R. Tepaev, E. Roslavtseva, A. Potapov, N. Shchigoleva, A. I. Materikin, K. Savostyanov","doi":"10.24287/1726-1708-2023-22-1-110-121","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-110-121","url":null,"abstract":"Exudative enteropathy is a clinical syndrome characterized by excessive loss of proteins through the gastrointestinal tract and is a rare complication of various gastrointestinal diseases. One of the rarest causes of protein malabsorption is Langerhans cell histiocytosis, which occurs as a result of inflammatory neoplasia of myeloid precursor cells caused by mutations in the mitogenactivated protein kinase pathway. Abnormal proliferation and accumulation of Langerhans cells in the intestinal wall leads to a violation of the outflow of lymph, and causes clinical manifestations characteristic of enteropathy. Given that the lesion of the gastrointestinal tract with histiocytosis from Langerhans cells occurs in 2–3% of cases, and the clinical signs are not highly specific, timely diagnosis is difficult. Delayed verification of the diagnosis and late initiation of adequate treatment are risk factors for multisystem lesions and lead to an unfavorable outcome. The literature describes a few observations of the onset or manifestation of the disease with symptoms of protein malabsorption. We present a rare clinical case of diagnosing histiocytosis from Langerhans cells in a young child with severe manifestations of exudative enteropathy at the onset. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.Refractory gastrointestinal symptoms require mandatory endoscopic and histological examination to identify rare causes of malabsorption. Timely initiation of targeted therapy with vemurafenib in combination with subsequent chemotherapy provided the child with a favorable prognosis and stable remission of the disease.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78679795","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 : 2023-02-14DOI: 10.24287/1726-1708-2023-22-1-139-146
E. K. Mgdsyan, D. Yukhacheva, E. A. Malakhova, D. Pershin, A. М. Kieva, E. Raikina, N. Kondratieva, E. Alekseeva, Y. Rodina, A. Shcherbina
X-linked agammaglobulinemia (XLA), or Bruton’s agammaglobulinemia, – is a primary immunodeficiency, caused by defects in the BTK gene encoding Bruton’s tyrosine kinase. The BTK defects lead to the arrest of B-lymphocyte development and, as a result, agammaglobulinemia. The disease manifests with recurrent infections starting in infancy. The gold standard of XLA treatment – intravenous or subcutaneous immunoglobulin substitution – proved effective in various multicenter studies and increases the quality of life of XLA patients. However, there are cases of delayed disease verification, and untimely delayed treatment, which leads to severe, recurrent infections and life-threatening conditions. We present a review of the literature and case report of an XLA patient with ecthyma gangrenosum. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.
{"title":"X-linked agammaglobulinemia: a review of literature and a case report","authors":"E. K. Mgdsyan, D. Yukhacheva, E. A. Malakhova, D. Pershin, A. М. Kieva, E. Raikina, N. Kondratieva, E. Alekseeva, Y. Rodina, A. Shcherbina","doi":"10.24287/1726-1708-2023-22-1-139-146","DOIUrl":"https://doi.org/10.24287/1726-1708-2023-22-1-139-146","url":null,"abstract":"X-linked agammaglobulinemia (XLA), or Bruton’s agammaglobulinemia, – is a primary immunodeficiency, caused by defects in the BTK gene encoding Bruton’s tyrosine kinase. The BTK defects lead to the arrest of B-lymphocyte development and, as a result, agammaglobulinemia. The disease manifests with recurrent infections starting in infancy. The gold standard of XLA treatment – intravenous or subcutaneous immunoglobulin substitution – proved effective in various multicenter studies and increases the quality of life of XLA patients. However, there are cases of delayed disease verification, and untimely delayed treatment, which leads to severe, recurrent infections and life-threatening conditions. We present a review of the literature and case report of an XLA patient with ecthyma gangrenosum. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82603711","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：