Pediatric Hematology/Oncology and Immunopathology最新文献

{"title":"Clinical features and treatment of hemophilia B","authors":"N. I. Zozulya, T. A. Andreeva, P. A. Zharkov, V. Vdovin","doi":"10.24287/1726-1708-2024-23-1-192-199","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-192-199","url":null,"abstract":"   Hemophilia B – a deficiency of blood coagulation factor IX (FIX) – is one of the most common hereditary coagulopathies along with hemophilia A and von Willebrand disease. As in hemophilia A, patients with hemophilia B require prophylactic treatment to prevent the development of bleeding and arthropathy, and there is a number of unsolved problems in their treatment. At the same time, the arsenal of drugs for the treatment of hemophilia B is significantly smaller compared to hemophilia A, and therefore the emergence of new drugs for the treatment of FIX deficiency is of great practical importance for doctors and patients. The article provides information about the pathogenesis and clinical course of hemophilia B, discusses the most promising areas in the treatment of this disease, such as innovative recombinant FIX molecules, rebalancing and gene therapy. In addition, we outlined clinical and laboratory criteria indicating the necessity to change treatment in patients with hemophilia B as well as presented clinical cases of patients who were switched to long-acting FIX products. The patients' parents gave their consent to the use of their children's data for research purposes and in publications.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" 33","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140687464","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}

{"title":"Immune checkpoint inhibitor therapy in children and adolescents with refractory/relapsed Hodgkin lymphoma: a case series","authors":"E. A. Tuzova, D. Evstratov, A. V. Pshonkin, M. N. Korsantiya, I. Fisyun, D. Litvinov, N. Myakova","doi":"10.24287/1726-1708-2024-23-1-159-164","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-159-164","url":null,"abstract":"   Ten-year progression-free survival in children, adolescents and young adults with relapsed/refractory Hodgkin lymphoma (r/r HL) does not exceed 50 %. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs), such as nivolumab and pembrolizumab, are successfully used for the treatment of adults with r/r HL. In this study, we analyzed our experience of ICI treatment of children and adolescents with r/r HL. This study was retrospective and included patients with r/r HL under 18 years of age, who received ICI therapy. Twenty patients were included. All of them had been treated with BV, 35 % (n = 7) of patients had undergone auto-HSCT before treatment with ICIs. Among all patients, 45% (n = 9) received ICIs for the first refractory relapse, 40 % (n = 8) due to refractory disease progression and 15 % (n = 3) received therapy for the second relapse. Two patients received ICIs in combination with other drugs, the response to therapy in 2 patients was unknown. Nine (56 %) of 16 patients achieved a metabolic response, one patient had no evidence of vital tumor cells based on the results of a biopsy of a lesion positive on positron emission tomography, thus a response was achieved in 10 (63%) patients. The survival rate analysis included 20 patients. Median follow-up from ICIs initiation was 1.2 years (interquartile range: 0.7–1.5 years). The probability of 1-year overall survival (OS) rate reaches 69 % (95 % confidence interval (CI) 46.4–91.6), 2-year OS – 60.4 % (95 % CI 35.1–85.7), 3-year OS – 40.3 % (95 % CI 4–76.6). In this study, we demonstrated the effectiveness of the treatment with ICIs as an element of therapy in children and adolescents with r/r HL, who had not responded to previous lines of therapy, including BV. The patients' parents gave consent to the use of their children's data, including photographs, for research purposes and in publications.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140686785","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}

{"title":"Modern aspects of hemophilia A diagnosis","authors":"A. V. Poletaev, E. Seregina, P. A. Zharkov","doi":"10.24287/1726-1708-2024-23-1-200-210","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-200-210","url":null,"abstract":"   The evolution of hemophilia treatment is rapidly developing. Both new factor replacement and non-factor therapy have appeared in recent years. One of the most important problems of factor replacement therapy is the relatively short half-life of coagulation factor VIII (FVIII), with an average of about 8–12 hours in adults, ranging in individual patients between 6 and 24 hours, and even shorter in younger children. This forces patients, especially children, to administer the drug quite often (3–4 times a week), reducing the quality of life and adherence to treatment. The appearance of recombinant FVIII products with an increased half-life allows to reduce the number of infusions per week, improving the quality of life of patients without compromising the safety and efficacy of treatment. However, the structure of these products leads to the changes in the results of laboratory tests of FVIII activity carried out to monitor the efficacy of treatment. In this article, we will consider the current methods of laboratory control of products with an increased half-life of FVIII currently available in Russia. We want to assess the discrepancy between the one-stage clotting method and chromogenic method for each FVIII product, as well as the laboratory's capabilities in monitoring non-factor and combined therapy for hemophilia A.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688659","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}

{"title":"Tolerability and toxicity of induction chemoimmunotherapy with dinutuximab beta in newly diagnosed patients with high-risk neuroblastoma","authors":"T. Shamanskaya, D. Y. Kachanov, N. S. Ivanov, L. L. Rabaeva, M. Yadgarov, O. S. Zatsarinnaya, D. Т. Utalieva, D. Litvinov, A. G. Rumyantsev, G. Novichkova","doi":"10.24287/1726-1708-2024-23-1-108-118","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-108-118","url":null,"abstract":"   Monoclonal antibodies (mAbs) directed against GD2 are used as part of post-consolidation treatment for high-risk neuroblastoma (NB) patients with minimal residual tumor after induction therapy. It has been reported that a good end-of-induction response is associated with better event-free survival and overall survival rates. The use of mAbs in combination with chemotherapy has been shown to be effective in treating patients with relapsed NB in several international studies. Thus, the need to achieve a good end-of-induction response in high-risk NB and the feasibility of combining chemotherapy with mAbs serve as a rationale for employing immunotherapy during induction treatment of newly diagnosed patients with NB. Here, we present the results of the first Russian single-center study on the use of chemoimmunotherapy (CIT) during induction treatment in newly diagnosed patients with high-risk NB. In this prospective study carried out at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between January and August 2023, we enrolled 5 high-risk stage 4 NB patients aged > 18 months. This study was approved by the Institutional Review Board and the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Healthcare of the Russian Federation (Protocol No. 10э/9-22 dated 10. 12. 2022). Therapy was carried out according to the modified GPOH NB2004 protocol. Starting from the 3rd course of induction, patients received 4 alternating courses of chemotherapy in combination with anti-G mAbs ch14.18/CHO (dinutuximab beta) at a dose of 10 mg/m2/day administered as a continuous infusion over 5 days. Toxicity was assessed as per the CTCAE 5.0 (Common Terminology Criteria for Adverse Events, version 5.0). A total of 20 courses of CIT were given. All patients completed induction therapy, with 3/5 (60%) achieving at least a partial response. There were no cases of unexpected severe toxicity or death. There were no pauses in the administration of mAb throughout all the CIT cycles, and all the patients received dinutuximab beta at full dose. Grade 3/4 toxicity was predominantly hematological. Non-hematological toxicity of grade ≥ III/IV included hypokalemia in 5/20 (25 %) courses, hypertension in 4/20 (20 %) courses and diarrhea in 3/20 (15 %) courses (due to viral infection). The need for opioid analgesics decreased with each successive course of treatment. The selected CIT regimen combining induction chemotherapy as per the GPOH NB2004 protocol and dinutuximab beta demonstrated safety and acceptable toxicity in newly diagnosed patients with high-risk stage 4 NB older than 18 months. Further multicenter cooperative studies will allow for the development of the optimal induction regimen consisting of chemotherapy and mAbs for improved survival in patients with high-risk NB.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"12 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140693006","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}

{"title":"Flow cytometric and cytomorphological definition of remission achievement in children with acute myeloid leukemia","authors":"E. Mikhailova, A. N. Dagestani, S. Kashpor, S. Plyasunova, T. Konyukhova, M. Dubrovina, K. Voronin, I. Kalinina, E. Zerkalenkova, Y. Olshanskaya, A. V. Popa, A. A. Maschan, G. Novichkova, A. Popov","doi":"10.24287/1726-1708-2024-23-1-73-85","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-73-85","url":null,"abstract":"   The achievement of clinical and hematological remission at the end of induction therapy is one of the key treatment response parameters in pediatric acute myeloid leukemia (AML). Besides conventional cytomorphological evaluation of bone marrow (BM) blast count, minimal residual disease (MRD) measurement has been widely applied in routine clinical practice in recent years.   The aim of the study was to compare the results of flow cytometric MRD evaluation with the results of cytomorphological BM investigation when assessing the achievement of remission at the end of induction in children with AML.   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. We analyzed BM samples obtained from 402 children with AML, who had been treated according to the AML-MRD-2018 protocol and undergone simultaneous cytometric and cytomorphological BM investigation at the end of induction. A myelogram count was performed on 500 nucleated cells per BM smear. MRD was measured by 10-color flow cytometry with the 0.1 % cut-off for reliable MRD-positivity. The threshold of 5 % blasts was used as the criterion of complete remission (CR). Overall concordance of the two methods was 83.3 % for the CR status confirmation: in 335 out of 402 patients, the presence or absence of CR was stated using both techniques. Half of the 67 discordant samples were obtained from patients with a significant monocytic component of the leukemic population: 14 (20.9 %) with AML M4 and 20 (29.9 %) with AML M5. Among all FAB subtypes, the highest concordance rate was noted in patients with M1 variant (91.7 %), while the worst comparability – in children with megakarioblastic leukemia (M7 type, 72.7 %). Failure to achieve CR by cytomorphology did not influence the outcome of the patients who achieved CR as confirmed by immunophenotyping. At the same time, for flow cytometric BM investigation, achieving MRD negativity (< 0.1%) was the most significant favorable outcome predictor even at this rather early stage. Moreover, relapse incidence in children who were in CR but MRD positive (≥ 0.1 %) was higher than in patients who did not achieve CR at the end of induction according to flow cytometry (MRD ≥ 5 %), especially in the intermediate-risk group. This difference can be explained by more intensive chemotherapy (FLAI instead of HAM cycle) given to patients who did not achieve CR at the end of induction, and patients in the intermediate-risk group were additionally re-stratified to a high-risk group with subsequent hematopoietic stem cell transplantation. Flow cytometric and cytomorphological BM examination for the CR status confirmation at the end of induction in children with AML demonstrated a relatively high concordance rate (83.3 %). CR achievement by cytomorphology does not influence final outcome, although for the flow cytometry conventional threshold of 5","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140690266","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}

{"title":"Pharmacokinetic parameters of simoctocog alfa in children with hemophilia A without inhibitors in real clinical practice","authors":"P. A. Zharkov, D. B. Florinskiy, E. Shiller","doi":"10.24287/1726-1708-2024-23-1-86-91","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-86-91","url":null,"abstract":"   In our country, experience in using simoctocog alfa in children with hemophilia A (HA) without inhibitors in real clinical practice is scarce and limited to few case reports without pharmacokinetic analysis.   Aim of the study: to investigate the pharmacokinetics of simoctocog alfa in children with HA in real clinical practice.   We carried out a retrospective analysis of data from medical records of children with HA treated with simoctocog alfa at a single healthcare center in the Russian Federation. For pharmacokinetic characterization of simoctocog alfa, we also measured the following parameters using the Sysmex 2000 Hematology System: factor VIII activity before the administration of simoctocog alfa, and then 4 hours and 24 hours after the infusion (one-stage clotting assay performed with Pathromtin SL reagent). All measured values were entered into the WAPPS-Hemo platform for the estimation of pharmacokinetic parameters, which were then used to calculate the expected activity of the deficient factor. Ethics committee approval was not required for this study because it involved the use of aggregated retrospective data from routine clinical practice that were fully anonymized. The study included 8 patients with severe and moderate HA. The median age at the time of pharmacokinetic study was 9 years 6 months. In most patients, 1 IU/kg of simoctocog alfa led to an increase in factor VIII activity of more than 1 %; the maximum and the minimum values were 1.7 % and 0.82 %, respectively. Four patients received adequate doses of factor concentrate (43–50 IU/kg), 1 patient received factor concentrate at an insufficient dose (22 IU/kg), and 3 patients received high doses of simoctocog alfa (60 IU/kg, 71 IU/kg and 95 IU/kg). The median ‘balanced’ half-life estimate for FVIII was 11.75 hours. The median ‘balanced’ estimates of time to reach 5 % FVIII activity (0.05 IU/mL), 2 % activity (0.02 IU/mL) (n = 5) and 1 % activity (0.01 IU/mL) (n = 3) were 53.5 hours, 71.5 hours and 82.5 hours, respectively. Our results obtained in clinical settings demonstrate that simoctocog alfa can be effectively used for prophylaxis in children with HA without inhibitors. It can be administered every other day to achieve high residual activity (at least 5 %) or every third day in patients with FVIII residual activity of at least 1 % in order to reduce the number of injections.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" 57","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140692008","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}

{"title":"Statistically significant improvement in hemophilia A control: a retrospective analysis of the effectiveness and safety of emicizumab in children with severe and inhibitor forms of hemophilia A","authors":"V. Petrov, I. Lavrentyeva, V. Vdovin, P. Svirin","doi":"10.24287/1726-1708-2024-23-1-99-107","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-99-107","url":null,"abstract":"   Hemophilia A presents a serious problem, especially in its severe and inhibitor forms, leading to severe bleeding and complications. The importance of studying the effectiveness and safety of new treatment approaches, particularly emicizumab, is undeniable for improving the quality of life of patients.   Aim: to evaluate the effectiveness and safety of emicizumab in the prevention of bleeding in children with severe and inhibitor forms of hemophilia A.   Ethical approval was not required since the study only involved the use of generalized retrospective data obtained during routine clinical practice. All data were depersonalized. A retrospective analysis of medical records of 45 children treated at the Morozov Children's Hospital from 2006 to 2022 was carried out. The study included two cohorts: those with severe hemophilia A and those with inhibitor forms. The analysis included an assessment of the frequency of bleeding and hemarthrosis episodes, hospital admissions, and adverse reactions. The analysis included data from 45 patients with hemophilia A who underwent treatment with emicizumab from 2018 to 2022. Of these, 30 children had a severe form of hemophilia A, and 15 had an inhibitor form. The median follow-up period for a severe form was 17 months, ranging from 12 to 23 months, while for an inhibitor form, it was 32 months, with a range of 11 to 51 months. In the group with severe hemophilia A, a statistically significant (p < 0.001) reduction in the frequency of all types of bleeding was observed: 96.7 % of children had no episodes of hemarthrosis during emicizumab therapy, compared to 46.7 % of patients previously treated with FVIII concentrates. No spontaneous hemarthrosis was registered. Similar results were observed in the group with an inhibitor form of hemophilia A: 93.3 % of children had no hemarthrosis episodes while using emicizumab compared to 13.3% during previous treatment with bypassing agents. Over the entire follow-up period, there were 3 bleedings in the cohort of children with severe hemophilia A and 1 bleeding in the cohort of children with inhibitor hemophilia A. Prior to the use of emicizumab, out of 391 bleeding episodes that occurred in 45 children, 218 were spontaneous. Adverse events were recorded in 7 children, manifesting as erythema at the injection site after the first or first and second emicizumab injections and resolving spontaneously. There were no other adverse events; 90 % of children with severe hemophilia A and 73.3 % of children with inhibitor hemophilia A did not report any adverse events during the use of emicizumab. Emicizumab demonstrates high effectiveness and safety in the treatment of children with severe hemophilia A, both with and without inhibitors. The drug significantly reduces the frequency of bleeding episodes and improves the quality of life of patients.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":" 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140690756","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}

{"title":"The use of blinatumomab in children with de novo Ph-negative B-lineage acute lymphoblastic leukemia and slow clearance of minimal residual disease","authors":"A. Popov, Y. Rumyantseva, E. Mikhailova, O. Bydanov, E. Zerkalenkova, Y. Olshanskaya, T. Verzhbitskaya, Zh. V. Permikin, G. Tsaur, S. Lagoyko, L. Zharikova, N. Myakova, N. Ponomareva, E. Boychenko, L. Fechina, G. Novichkova, A. Karachunskiy","doi":"10.24287/1726-1708-2024-23-1-63-72","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-63-72","url":null,"abstract":"   Children with acute lymphoblastic leukemia (ALL) and slow clearance of minimal residual disease (MRD) demonstrate a significantly worse outcome as compared to those with fast response to chemotherapy. Bispecific monoclonal antibody blinatumomab is the key drug for CD19-directed immunotherapy which opens wide opportunities for the elimination of MRD in patients with B-cell precursor ALL (BCP-ALL).   Aim of the study – to evaluate the effectiveness of blinatumomab for MRD elimination in children with BCP-ALL and slow MRD clearance treated by the “ALL-MB 2015” 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. Patients from the “ALL-MB 2015” trial who demonstrated slow MRD clearance at the end of induction were included in the current study. MRD monitoring was performed by multicolor flow cytometry modified with respect to possible CD19 loss during targeted treatment. Threshold of 0.001% was used for MRD positivity definition. Between February 2020 and August 2023, 228 children with de novo Ph-negative KMT2A-negative BCP-ALL were defined as slow MRD responders according to the criteria of the “Moscow-Berlin” group. Fifty of them were treated with blinatumomab because of slow MRD clearance. Blinatumomab course was given immediately after induction in 23 children, after Consolidation I – in 14 patients, after Consolidation II – in 11 patients, while two children received immunotherapy prior to maintenance. After completion of blinatumomab course, 23 patients continued protocol treatment, 21 received maintenance only, two were treated with high-risk blocks and four received hematopoietic stem cell transplantation. Only 2 of 50 (4.0 %) patients remained MRD-positive after completion of blinatumomab course. By the end of December 2023, only two adverse events were registered: one relapse and one remission death. Two-year event-free survival was 94.7 % (standard error 3.6 %), while cumulative incidence of relapse was 2.6 % (standard error 2.7 %). Outcome in these 50 patients was much better in comparison with 178 children with a slow MRD response who did not receive blinatumomab. The use of blinatumomab in children with de novo Ph-negative BCP-ALL with slow MRD clearance allows achieving MRD-negative remission in nearly all cases. Although a longer follow-up is necessary for the reliable conclusion of CD19-directed therapy effectiveness, the promising results are obtained in the current study in this unfavorable patient group.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"22 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140696410","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}

{"title":"The impact of immunoarchitectural patterns on clinical presentation and response to therapy in children with nodular lymphocyte predominant Hodgkin lymphoma","authors":"M. A. Senchenko, D. Abramov, N. Myakova, D. M. Konovalov","doi":"10.24287/1726-1708-2024-23-1-25-36","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-25-36","url":null,"abstract":"   In recent years, there has been a trend towards de-escalation of therapy in patients with early stages of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) which enables reduction in the frequency of late effects of chemo- and radiation therapy while still maintaining their effectiveness. Patients with stage I NLPHL only require excisional biopsy of lymph nodes. If complete remission cannot be achieved by surgery alone or if patients have stage II NLPHL, 3 cycles of low-dose CVP (cyclophosphamide, vinblastine, prednisolone) chemotherapy are administered. In some cases, patients show incomplete response to therapy with subsequent progression of the disease. Hence, the search for factors of unfavorable clinical course of NLPHL still continues, with an immunoarchitectural pattern potentially being one of them.   Here, we aimed to compare clinical features, treatment responses and relapse rates in patients with NLPHL based on the type of an immunoarchitectural pattern.   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. In our study, we included a cohort of 49 patients (39 boys, 10 girls) aged 2 to 18 years (median age: 10 years) with diagnosed NLPHL who were divided into 2 groups based on histological features of the disease: typical patterns (n = 21, 42.9 %) and atypical patterns (n = 28, 57.1 %). The two groups were compared using the exact Fisher test. Thirty-three patients had early stage I–II disease at baseline, 14 patients had stage III disease, and 2 patients were diagnosed with stage IV lymphoma affecting the liver and lungs in one case and bones in the other. Clinical characteristics (such as disease stage, B symptoms, the involvement of mediastinal and intra-abdominal lymph nodes) didn’t vary much between the groups, the only exception being the presence/absence of bulky disease (≥ 6 cm) (p = 0.0064). A higher rate of partial response to therapy and disease progression frequency were revealed in the group of atypical patterns (typical: n = 1/21, 4.8 % vs atypical: n = 14/28, 50 %; p = 0.00061). This group was also characterized by a higher relapse rate (typical patterns: n = 1/21, 4.8 % vs atypical: n = 5/28, 17.9 %; p = 0.219). The overall survival rate was 100%, with a median follow-up of 28 (3–108) months. In our study, we revealed a higher incidence of adverse outcomes in the patients with atypical NLPHL patterns compared to the group with typical patterns. The prognostic value of immunoarchitectural patterns needs to be explored more thoroughly, as they have the potential to become one of the criteria for risk stratification of patients with NLPHL.","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"32 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140701970","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}

{"title":"Bispecific monoclonal antibody blinatumomab in the first-line therapy of B-lineage acute lymphoblastic leukemia in children and adolescents: interim results of the Russian Ministry of Health approbation protocol","authors":"A. Karachunskiy, Y. Rumyantseva, L. Zharikova, O. Bydanov, S. Lagoyko, A. Popov, E. Mikhailova, Y. Olshanskaya, E. Zerkalenkova, N. Myakova, D. Litvinov, M. I. Abu-Dzhabal, L. Khachatryan, A. V. Pshonkin, N. Ponomareva, Y. Dinikina, T. T. Valiev, S. R. Varfolomeeva, G. Novichkova","doi":"10.24287/1726-1708-2024-23-1-14-24","DOIUrl":"https://doi.org/10.24287/1726-1708-2024-23-1-14-24","url":null,"abstract":"   The bispecific monoclonal antibody blinatumomab (CD19/CD3) is widely and successfully used to treat children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Advances have also led to the use of immunotherapy in children with primary BCP-ALL. This paper presents the effectiveness of a single blinatumomab course instead of consolidation chemotherapy and with short maintenance therapy in primary BCP-ALL patients. 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. Between February 2020 and November 2022, 165 children with non-high-risk BCP-ALL (according to clinical stratification criteria defined in the study) were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received conventional risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved complete morphological remission at the end of induction received 15 µg/m2/day of blinatumomab immediately after induction for 4 weeks, followed by 12 months of maintenance therapy. Minimal residual disease (MRD) was measured using multicolor flow cytometryat the end of induction, then immediately after blinatumomab course, and then four times during maintenance therapy at threemonth intervals. All 165 patients successfully completed induction therapy and achieved complete hematological remission. All had their MRD measured at the end of induction. One hundred thirty-six (82.2%) patients were MRD-negative, and the remaining 29 patients showed various levels of MRD positivity. MRD was assessed in all 164 patients who completed the blinatumomab course. One patient had blinatumomab discontinued due to acute neurotoxicity and was subsequently treated according to the intermediate-risk ALL-MB 2015 protocol. All but one patient achieved MRD negativity after blinatumomab course, regardless of MRD value at the end of induction. One adolescent girl with a high MRD level after induction remained MRD positive after blinatumomab course and further received high-risk therapy with allogeneic hematopoietic stem cell transplantation. At the time of analysis, 162 children had completed all therapy, including 12 months of maintenance. MRD was examined in 151 of them, and all were MRD negative. Over a 4-year study period with a median follow-up of 2.5 years, 10 relapses were registered: 4 in the standard-risk group and 6 in the intermediate-risk group. The 4-year event-free survival was 89.1 ± 3.7 % for all patients, 92.0 ± 4.2 % and 82.8 ± 8.1 % for the standard and intermediate risk groups, respectively. At the time of analysis, all patients were alive; no deaths were registered. Although the presented results are preliminary and more time is needed for definitive conclusions, a 4-week 15 µg/m2/day blinatumomab course immediately after induction followed by 12 months of maintenance therapy is effective in ach","PeriodicalId":38370,"journal":{"name":"Pediatric Hematology/Oncology and Immunopathology","volume":"176 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140706590","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}