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Clinical features of multiple myeloma with bone plasmacytomas 多发性骨髓瘤合并骨浆细胞瘤的临床特点
Q4 Medicine Pub Date : 2023-03-14 DOI: 10.17650/1818-8346-2023-18-1-48-56
E. A. Mamaeva, M. V. Soloveva, M. Solovev, A. Kovrigina, T. P. Danilina, L. Mendeleeva
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引用次数: 0
Clinical case of a 44-year-old patient with newly diagnosed peripheral T-cell lymphoma unspecified (Lennert’s lymphoma) and Loeffler’s endocarditis 44岁新诊断外周t细胞淋巴瘤(Lennert淋巴瘤)合并Loeffler心内膜炎的临床病例
Q4 Medicine Pub Date : 2023-03-14 DOI: 10.17650/1818-8346-2023-18-1-39-47
Yu. E. Ryabukhina, O. L. Timofeeva, A. A. Akhobekov, P. A. Zeynalova, F. М. Abbasbeyli, G. Allakhverdieva, A. G. Zhukov, V. V. Fedotov, L. A. Shestakova
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引用次数: 0
Features of acute megakaryoblastic leukemia diagnosis in a child with Down syndrome 唐氏综合征患儿急性巨核母细胞白血病的诊断特点
Q4 Medicine Pub Date : 2023-03-14 DOI: 10.17650/1818-8346-2023-18-1-31-38
N. Guskova, O. Selyutina, I. Lysenko, Y. Kozel, O. V. Kozyuk, V. V. Dmitrieva, M. A. Baranenkova, A. Nozdricheva
{"title":"Features of acute megakaryoblastic leukemia diagnosis in a child with Down syndrome","authors":"N. Guskova, O. Selyutina, I. Lysenko, Y. Kozel, O. V. Kozyuk, V. V. Dmitrieva, M. A. Baranenkova, A. Nozdricheva","doi":"10.17650/1818-8346-2023-18-1-31-38","DOIUrl":"https://doi.org/10.17650/1818-8346-2023-18-1-31-38","url":null,"abstract":"","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"237 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75099421","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}
引用次数: 0
Treatment outcomes for acute T-lymphoblastic leukemias/lymphomas: data from the ALL-2016 multicenter prospective randomized trial 急性t淋巴细胞白血病/淋巴瘤的治疗结果:来自ALL-2016多中心前瞻性随机试验的数据
Q4 Medicine Pub Date : 2023-03-13 DOI: 10.17650/1818-8346-2023-18-1-20-30
O. Aleshina, I. Galtseva, E. Kotova, G. I. Isinova, T. Obukhova, V. Dvirnik, A. Sudarikov, M. Grishunina, O. Samoilova, K. Kaplanov, V. Lapin, S. Bondarenko, E. Fokina, N. Minaeva, T. Konstantinova, Y. Sveshnikova, E. Zinina, A. Antipova, O. Baranova, E. Borisenkova, Y. Davydova, N. M. Kapranov, S. Kulikov, Y. Chabaeva, V. Troitskaya, E. Parovichnikova
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引用次数: 1
Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience 低甲基化药物联合BCL-2抑制剂治疗复发性急性髓性白血病:S.P. Botkin医院经验
Q4 Medicine Pub Date : 2023-03-13 DOI: 10.17650/1818-8346-2023-18-1-12-19
M. Granatkin, E. Nikitin, M. Kislova, E. Mikhailov, V. Doronin, S. Minenko, M. Okuneva, A. V. Antonova, N. V. Degtyareva, M. Pochtar, S. A. Lugovskaya, Y. Kobzev, V. Ptushkin, E. Rimashevskaya
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引用次数: 0
Свободно циркулирующая ДНК в плазме у пациентов с диффузной В-крупноклеточной лимфомой и В-клеточной лимфомой высокой степени злокачественности (‘double hit’/’triple hit’) 大细胞淋巴瘤和恶性淋巴瘤患者血浆中自由流动的dna。
Q4 Medicine Pub Date : 2023-03-03 DOI: 10.21320/2500-2139-2023-16-2-200-208
Светлана Юрьевна Смирнова, Е. Е. Никулина, Н. Г. Габеева, Д. А. Королева, С. А. Татарникова, А. К. Смольянинова, Э. Г. Гемджян, Е. Е. Звонков, А. Б. Судариков
Aim. To study plasma cell-free DNA (pcfDNA) concentration and B-cell clonality in patients with diffuse large B-cell (DLBCL) and B-cell high-grade lymphomas prior to and at different stages of chemotherapy as well as the correlation between the data obtained and clinical and laboratory parameters. Materials & Methods. The study enrolled 23 DLBCL patients and 7 healthy donors (HD). Plasma was prepared from whole blood by centrifugation, pcfDNA was isolated with the commercial kit Qiagen (Germany). The concentration of pcfDNA was determined using fluorometer Qubit (USA). В-cell clonality was estimated by immunoglobulin gene analysis (BIOMED-2 protocol) in the tumor tissue and bone marrow core biopsy specimens obtained on diagnosis date as well as in the pcfDNA at 5 end points: prior to chemotherapy and after cycles 1, 2, 3, and 4. Results. Prior to therapy, all DLBCL patients showed significantly higher pcfDNA concentration than HD. Immunochemotherapy cycle 1 resulted in considerable increase in pcfDNA concentration. After cycle 2 and subsequent cycles, pcfDNA concentration gradually decreased. After cycle 4, the mean pcfDNA concentration was comparable with that of HD. In 95 % of patients В-cell clonality in pcfDNA corresponded to that identified in the tumor specimen. After immunochemotherapy cycle 1, В-cell clonality was detected in 50 % of patients, after cycle 2 it was shown by 15 %. Only 1 female patient retained В-cell clonality after therapy cycles 3 and 4. In HD, no В-cell clonality in pcfDNA was identified. Prior to therapy, the analysis revealed no correlation of either pcfDNA concentration or В-cell clonality in pcfDNA with age, sex, tumor spread, presence or absence of extranodal lesions, proliferation index Ki-67, and lactate dehydrogenase concentration. Conclusion. In patients with malignant hematological tumors, pcfDNA seems to be an interesting, easily accessible biological material deserving further investigation. Any studies of pcfDNA require long-term dynamical analysis and standardized methods of collection, storage and processing of the data obtained. In the long run, with more and more information, pcfDNA can become an important diagnostic marker of tumor heterogeneity and a reliable relapse predictor.
的目标。研究弥漫性大b细胞(DLBCL)和b细胞高级别淋巴瘤患者化疗前和化疗不同阶段的血浆游离DNA (pcfDNA)浓度和b细胞克隆性,以及所获得的数据与临床和实验室参数的相关性。 材料,方法。该研究招募了23名DLBCL患者和7名健康供体(HD)。全血离心制备血浆,用Qiagen(德国)商用试剂盒分离pcfDNA。pcfDNA浓度采用Qubit(美国)荧光仪测定。通过免疫球蛋白基因分析(BIOMED-2方案)在诊断日期获得的肿瘤组织和骨髓核心活检标本以及5个终点的pcfDNA中估计В-cell克隆性:化疗前和周期1,2,3和4后。 结果。治疗前,所有DLBCL患者的pcfDNA浓度均明显高于HD。免疫化疗周期1导致pcfDNA浓度显著增加。周期2及后续周期后,pcfDNA浓度逐渐降低。第4周期后,pcfDNA的平均浓度与HD相当。95%的患者В-cell pcfDNA的克隆性与肿瘤标本中的克隆性一致。免疫化疗第1周期后,50%的患者检测到В-cell克隆,第2周期后,15%的患者显示出克隆。只有1名女性患者在治疗周期3和4后保留В-cell克隆。HD患者未发现pcfDNA В-cell克隆。治疗前,分析显示pcfDNA浓度或В-cell pcfDNA克隆与年龄、性别、肿瘤扩散、有无结外病变、增殖指数Ki-67和乳酸脱氢酶浓度均无相关性。结论。在恶性血液肿瘤患者中,pcfDNA似乎是一种有趣的、容易获得的生物材料,值得进一步研究。任何对pcfDNA的研究都需要长期的动态分析和收集、存储和处理所获得数据的标准化方法。从长远来看,随着信息的越来越多,pcfDNA可以成为肿瘤异质性的重要诊断指标和可靠的复发预测指标。
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 Materials & Methods. The study enrolled 23 DLBCL patients and 7 healthy donors (HD). Plasma was prepared from whole blood by centrifugation, pcfDNA was isolated with the commercial kit Qiagen (Germany). The concentration of pcfDNA was determined using fluorometer Qubit (USA). В-cell clonality was estimated by immunoglobulin gene analysis (BIOMED-2 protocol) in the tumor tissue and bone marrow core biopsy specimens obtained on diagnosis date as well as in the pcfDNA at 5 end points: prior to chemotherapy and after cycles 1, 2, 3, and 4.
 Results. Prior to therapy, all DLBCL patients showed significantly higher pcfDNA concentration than HD. Immunochemotherapy cycle 1 resulted in considerable increase in pcfDNA concentration. After cycle 2 and subsequent cycles, pcfDNA concentration gradually decreased. After cycle 4, the mean pcfDNA concentration was comparable with that of HD. In 95 % of patients В-cell clonality in pcfDNA corresponded to that identified in the tumor specimen. After immunochemotherapy cycle 1, В-cell clonality was detected in 50 % of patients, after cycle 2 it was shown by 15 %. Only 1 female patient retained В-cell clonality after therapy cycles 3 and 4. In HD, no В-cell clonality in pcfDNA was identified. Prior to therapy, the analysis revealed no correlation of either pcfDNA concentration or В-cell clonality in pcfDNA with age, sex, tumor spread, presence or absence of extranodal lesions, proliferation index Ki-67, and lactate dehydrogenase concentration.
 Conclusion. In patients with malignant hematological tumors, pcfDNA seems to be an interesting, easily accessible biological material deserving further investigation. Any studies of pcfDNA require long-term dynamical analysis and standardized methods of collection, storage and processing of the data obtained. In the long run, with more and more information, pcfDNA can become an important diagnostic marker of tumor heterogeneity and a reliable relapse predictor.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135339669","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}
引用次数: 0
Classical Hodgkin Lymphoma: Tumor Structure and Prognostic Value of the Immune Microenvironment 经典霍奇金淋巴瘤:肿瘤结构和免疫微环境的预后价值
Q4 Medicine Pub Date : 2023-03-03 DOI: 10.21320/2500-2139-2023-16-3-242-262
Артем Александрович Гусак, К. В. Лепик, Л. В. Федорова, В. В. Маркелов, В. В. Байков
Classical Hodgkin lymphoma (cHL) is a unique malignant lymphoid neoplasm characterized by tumor (Hodgkin and Reed-Sternberg) cells in the inflammatory and immunosuppressive microenvironment. The cHL microenvironment is a complex dynamic environment with immune cells, stromal elements, and extracellular matrix components, all of them interacting with each other and with tumor cells. This interaction basically underlies both disease progression and response to therapy. Currently, there is a growing interest in studying the structure and functions of cHL microenvironment, its prognostic value, and the potential of its components to be used as new therapeutic targets. During the last decade, the outcomes of refractory cHL treatment have considerably improved, in particular due to the administration of such PD-1 inhibitors as nivolumab and pembrolizumab. High cHL sensitivity to anti-PD-1 therapy can be accounted for by the PD-1/PD-L1-associated niche being formed in the tumor tissue as a result of intensive PD-L1 expression by tumor cells and macrophages as well as the expression of its PD-1 receptor by T-cells and M2-macrophages. More and more information becomes available about the possible mechanisms of antitumor response in anti-PD-1 treated cHL patients which seems to contradict the traditional understanding of CD8-mediated response in solid tumors. Cytotoxic effects of anti-PD-1 therapy in cHL tissues are likely to result from the interaction between tumor cells, macrophages, and CD4-positive Т-lymphocytes. This review discusses structural and regulatory relationships between tumor cells and microenvironment components, deals with new therapy approaches using various microenvironment components as targets, and summarizes currently available knowledge on prognosis based on the study of cHL microenvironment.
经典霍奇金淋巴瘤(Classical Hodgkin lymphoma, cHL)是一种独特的恶性淋巴样肿瘤,以肿瘤(Hodgkin和Reed-Sternberg)细胞处于炎症和免疫抑制微环境为特征。cHL微环境是一个复杂的动态环境,免疫细胞、基质成分、细胞外基质成分相互作用,并与肿瘤细胞相互作用。这种相互作用基本上是疾病进展和治疗反应的基础。目前,人们对cHL微环境的结构和功能、预后价值以及其成分作为新的治疗靶点的潜力的研究越来越感兴趣。在过去的十年中,难治性cHL治疗的结果有了很大的改善,特别是由于使用了nivolumab和pembrolizumab等PD-1抑制剂。cHL对抗PD-1治疗的高敏感性可能是由于肿瘤细胞和巨噬细胞强烈表达PD-L1,以及t细胞和m2巨噬细胞表达PD-1受体,从而在肿瘤组织中形成了PD-1/PD-L1相关生态位。越来越多的关于抗pd -1治疗的cHL患者抗肿瘤反应的可能机制的信息似乎与传统的cd8介导的实体肿瘤反应的理解相矛盾。抗pd -1治疗在cHL组织中的细胞毒性作用可能是肿瘤细胞、巨噬细胞和cd4阳性Т-lymphocytes之间相互作用的结果。本文综述了肿瘤细胞与微环境成分之间的结构和调控关系,探讨了以各种微环境成分为靶点的新治疗方法,并总结了目前基于cHL微环境研究的预后知识。
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引用次数: 0
Динамика выявления РНК вируса SARS-CoV-2 у пациентов и сотрудников ФГБУ «НМИЦ гематологии» Минздрава России в первые 2 года пандемии новой коронавирусной инфекции COVID-19 俄罗斯卫生部门患者和工作人员SARS-CoV-2的rna检测动态
Q4 Medicine Pub Date : 2023-03-03 DOI: 10.21320/2500-2139-2023-16-2-186-191
Оксана Газимагомедовна Старкова, Д. С. Тихомиров, А. Ю. Крылова, И. О. Снежко, Е. Н. Овчинникова, О. А. Алешина, Т. А. Туполева, Т. В. Гапонова
Background. COVID-19 required fundamental changes in healthcare management, also in medical care for oncological and hematological patients. Visits to healthcare organizations were minimized, 75 % of doctor appointments were converted to telemedicine consultations. The solutions aimed at preventing further spread of COVID-19 included establishing of observational units, distinguishing between patient and employee flows, regular SARS-CoV-2 RNA testing, reducing hospital stays and transferring patients with positive COVID-19 tests to the remodeled hospitals specializing in the novel coronavirus infection, as well as providing only emergency medical treatment and, as far as feasible, converting systemic chemotherapy to per os treatment, etc. Aim. To assess SARS-CoV-2 RNA detection dynamics at the National Research Center for Hematology from April 2020 to January 2022 during the implementation of epidemic control measures. Materials & Methods. The study was based on SARS-CoV-2 RNA testing of naso- and oropharyngeal samples obtained from patients and employees of the National Research Center for Hematology (hereafter referred to as Center). Besides, bronchoalveolar lavage fluid, lung tissue biopsies, and sputum were examined for SARS-CoV-2 RNA. The study was performed at the Center’s Virusology Department with the use of Sintol reagent kit “ПЦР-РВ-2019-nCov”. Results. The study was based on 107,470 tests: 58,141 (54 %) of employees and 45,126 (46 %) of patients; 35,508 (33 %) of men and 71,962 (67 %) of women. In 1318 cases SARS-CoV-2 RNA was detected which accounted for 1.15 % of total test number. In the groups of employees/patients, virus detection rate was 1.42 %/1.09 % (p < 0.001), and in male/female groups it was 1.3 %/1.2 %, respectively (p = 0.154). The rate of infection in the groups of tumor and non-tumor hematological patients, as proved by SARS-CoV-2 RNA testing, was 1.24 % and 0.92 %, respectively (p = 0.147). In employees and patients of the Center, a wave-like virus detection rate was observed. The largest number of infections was registered in April-June 2020 (79 patients and 170 employees), October-December 2020 (126 patients and 190 employees), and January 2022 (59 patients and 203 employees), which corresponded to the first, second, and fifth COVID-19 waves in Russia. Conclusion. The analysis of data obtained at the National Research Center for Hematology demonstrated a wave-like SARS-CoV-2 RNA detection rate in employees and patients of the Center, which corresponded to the general trend in Russia. The SARS-CoV-2 RNA detection rate did not depend on sex of subjects under study and was not significantly different in the groups of tumor and non-tumor hematological patients. Although the patients in hematological hospital are more exposed to the risk of severe infectious complications, they showed laboratory markers for COVID-19 less frequently than the Center employees.
背景。COVID-19要求医疗保健管理以及肿瘤和血液患者的医疗护理发生根本性变化。对医疗机构的访问减少到最低限度,75%的医生预约被转换为远程医疗咨询。防止新冠病毒进一步传播的解决方案包括:建立观察单位,区分患者和员工流动,定期进行SARS-CoV-2 RNA检测,缩短住院时间,将COVID-19检测阳性的患者转移到改造后的新型冠状病毒感染专科医院,只提供紧急医疗治疗,并尽可能将全身化疗转为全身治疗等;的目标。评估2020年4月至2022年1月国家血液学研究中心实施疫情控制措施期间SARS-CoV-2 RNA检测动态。材料,方法。该研究基于对从国家血液学研究中心(以下简称中心)的患者和员工获得的鼻和口咽样本进行的SARS-CoV-2 RNA检测。此外,对支气管肺泡灌洗液、肺组织活检和痰液进行了SARS-CoV-2 RNA检测。本研究在中心病毒学部进行,使用Sintol试剂盒“ПЦР-РВ-2019-nCov”。 结果。该研究基于107,470项测试:58141名(54%)员工和45126名(46%)患者;35,508名(33%)男性和71,962名(67%)女性。1318例检测到SARS-CoV-2 RNA,占总检测数的1.15%。在员工/患者组中,病毒检出率为1.42% / 1.09% (p <0.001),男女组分别为1.3% / 1.2% (p = 0.154)。经SARS-CoV-2 RNA检测,肿瘤和非肿瘤血液病患者的感染率分别为1.24%和0.92% (p = 0.147)。在该中心的员工和患者中,观察到波浪状病毒检出率。感染人数最多的是2020年4月至6月(79名患者和170名员工)、2020年10月至12月(126名患者和190名员工)和2022年1月(59名患者和203名员工),这与俄罗斯的第一波、第二波和第五波COVID-19相对应。结论。对国家血液学研究中心获得的数据进行分析后发现,该中心员工和患者的SARS-CoV-2 RNA检出率呈波浪状,这与俄罗斯的总体趋势相吻合。SARS-CoV-2 RNA检出率不依赖于研究对象的性别,在肿瘤和非肿瘤血液病患者组中无显著差异。尽管血液科医院的患者更容易出现严重的感染并发症,但他们出现COVID-19实验室标志物的频率低于中心员工。
{"title":"Динамика выявления РНК вируса SARS-CoV-2 у пациентов и сотрудников ФГБУ «НМИЦ гематологии» Минздрава России в первые 2 года пандемии новой коронавирусной инфекции COVID-19","authors":"Оксана Газимагомедовна Старкова, Д. С. Тихомиров, А. Ю. Крылова, И. О. Снежко, Е. Н. Овчинникова, О. А. Алешина, Т. А. Туполева, Т. В. Гапонова","doi":"10.21320/2500-2139-2023-16-2-186-191","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-2-186-191","url":null,"abstract":"Background. COVID-19 required fundamental changes in healthcare management, also in medical care for oncological and hematological patients. Visits to healthcare organizations were minimized, 75 % of doctor appointments were converted to telemedicine consultations. The solutions aimed at preventing further spread of COVID-19 included establishing of observational units, distinguishing between patient and employee flows, regular SARS-CoV-2 RNA testing, reducing hospital stays and transferring patients with positive COVID-19 tests to the remodeled hospitals specializing in the novel coronavirus infection, as well as providing only emergency medical treatment and, as far as feasible, converting systemic chemotherapy to per os treatment, etc.&#x0D; Aim. To assess SARS-CoV-2 RNA detection dynamics at the National Research Center for Hematology from April 2020 to January 2022 during the implementation of epidemic control measures.&#x0D; Materials &amp; Methods. The study was based on SARS-CoV-2 RNA testing of naso- and oropharyngeal samples obtained from patients and employees of the National Research Center for Hematology (hereafter referred to as Center). Besides, bronchoalveolar lavage fluid, lung tissue biopsies, and sputum were examined for SARS-CoV-2 RNA. The study was performed at the Center’s Virusology Department with the use of Sintol reagent kit “ПЦР-РВ-2019-nCov”.&#x0D; Results. The study was based on 107,470 tests: 58,141 (54 %) of employees and 45,126 (46 %) of patients; 35,508 (33 %) of men and 71,962 (67 %) of women. In 1318 cases SARS-CoV-2 RNA was detected which accounted for 1.15 % of total test number. In the groups of employees/patients, virus detection rate was 1.42 %/1.09 % (p < 0.001), and in male/female groups it was 1.3 %/1.2 %, respectively (p = 0.154). The rate of infection in the groups of tumor and non-tumor hematological patients, as proved by SARS-CoV-2 RNA testing, was 1.24 % and 0.92 %, respectively (p = 0.147). In employees and patients of the Center, a wave-like virus detection rate was observed. The largest number of infections was registered in April-June 2020 (79 patients and 170 employees), October-December 2020 (126 patients and 190 employees), and January 2022 (59 patients and 203 employees), which corresponded to the first, second, and fifth COVID-19 waves in Russia.&#x0D; Conclusion. The analysis of data obtained at the National Research Center for Hematology demonstrated a wave-like SARS-CoV-2 RNA detection rate in employees and patients of the Center, which corresponded to the general trend in Russia. The SARS-CoV-2 RNA detection rate did not depend on sex of subjects under study and was not significantly different in the groups of tumor and non-tumor hematological patients. Although the patients in hematological hospital are more exposed to the risk of severe infectious complications, they showed laboratory markers for COVID-19 less frequently than the Center employees.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"284 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135339819","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}
引用次数: 0
Эффективность и токсичность индукционной терапии у пациентов с впервые диагностированным системным AL-амилоидозом: результаты проспективного одноцентрового клинического исследования 第一次诊断为系统性淀粉样变性患者的诱导疗法效率和毒性:前期单中心临床试验的结果
Q4 Medicine Pub Date : 2023-03-03 DOI: 10.21320/2500-2139-2023-16-2-166-173
И. Г. Рехтина, Виктория Александровна Хышова, М. В. Соловьев, Л. П. Менделеева
Aim. To assess the outcomes of induction therapy in patients with newly diagnosed systemic AL Amyloidosis (AL-А). Materials & Methods. The prospective single-center clinical study enrolled 60 patients (32 women and 28 men) with newly diagnosed systemic AL-A stage I/IIIA. The median age was 59 years (range 34–74 years). In 57 patients, BorСyDex (bortezomib, cyclophosphamide, dexamethasone) was used as first-line therapy. RCd regimen (lenalidomide, cyclophosphamide, dexamethasone) was administered to 3 patients. Patients with the lack of efficacy or pronounced toxicity (n = 24) received second-line induction therapy with lenalidomide or melphalan combined with dexamethasone. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was administered to 11 (18 %) patients. Results. Hematologic targeted response (complete remission [CR] and very good partial remission [VGPR]) to BorCyDex was achieved in 62 % of patients. As a result of all lines of induction therapy, including auto-HSCT, targeted response increased to 69 %, specifically in 7/51 (14 %) patients with stringent CR (sCR), 8/51 (16 %) patients with CR, and 20/51 (39 %) patients with VGPR. Renal response after BorCyDex was registered in 10/38 (26 %) patients, 6/31 (19 %) patients showed heart response, and in 4/5 (80 %) patients liver response was reported. All therapy lines with auto-HSCT led to organ response (in ≥ 1 organ) in 15/46 (32 %) patients. Clinical response was shown by all patients with achieved sCR, by 67 % of patients with CR, and 47 % with VGPR (p = 0.04). With lower hematologic response rates, no clinical improvement was observed. With follow-up duration of 36 months, the median disease-free survival (without signs of hematologic and clinical progression) was not achieved. The 3-year overall survival was 80 %. Mortality during induction therapy was 10 % (6 patients died, including 2 patients with COVID-19). The planned 6 courses of BorCyDex could be completed only in 13 (23 %) out of 55 patients. During the induction therapy using BorCyDex, 4 patients died. The treatment was discontinued in 7/55 (12 %) patients due to its inefficacy and in 22/55 (39 %) patients because of severe peripheral and autonomic polyneuropathy. Nine (16 %) out of 55 patients with the achieved hematologic response showed excessive NT-proBNP elevation, which was accompanied by cardiovascular complications and provided ground for chemotherapy withdrawal. Conclusion. Low organ recovery rate remains the most challenging issue for AL-A treatment. Hematologic response depth (achieved CR) is a critical factor in achieving clinical effect. The obtained data confirmed high toxicity of BorCyDex regimen in AL-A patients. Despite the advances in AL-А therapy which are associated with the use of proteasome inhibitors, treatment of this disease calls for new and more effective approaches.
的目标。评估诱导治疗对新诊断的全身性AL淀粉样变性(AL-А)患者的疗效。 材料,方法。这项前瞻性单中心临床研究纳入了60例新诊断的系统性AL-A I/IIIA期患者(32名女性和28名男性)。中位年龄为59岁(范围34-74岁)。57例患者使用BorСyDex(硼替佐米、环磷酰胺、地塞米松)作为一线治疗。3例患者采用来那度胺、环磷酰胺、地塞米松RCd方案。无效或明显毒性的患者(n = 24)接受来那度胺或美法兰联合地塞米松的二线诱导治疗。11例(18%)患者接受自体造血干细胞移植(auto-HSCT)大剂量化疗。结果。62%的患者获得了BorCyDex的血液学靶向缓解(完全缓解[CR]和非常好的部分缓解[VGPR])。包括自体造血干细胞移植在内的所有诱导疗法的结果是,靶向反应增加到69%,特别是在7/51(14%)严重CR (sCR)患者,8/51 (16%)CR患者和20/51 (39%)VGPR患者中。10/38例(26%)患者在服用BorCyDex后出现肾脏反应,6/31例(19%)患者出现心脏反应,4/5例(80%)患者出现肝脏反应。所有auto-HSCT治疗线在15/46(32%)患者中导致器官反应(≥1个器官)。所有达到sCR的患者,67%的CR患者和47%的VGPR患者均有临床反应(p = 0.04)。由于血液学反应率较低,没有观察到临床改善。随访36个月,中位无病生存期(无血液学和临床进展迹象)未达到。3年总生存率为80%。诱导治疗期间的死亡率为10%(6例死亡,包括2例COVID-19患者)。55例患者中只有13例(23%)完成了计划的6个疗程的BorCyDex治疗。BorCyDex诱导治疗期间死亡4例。7/55(12%)的患者因治疗无效而停止治疗,22/55(39%)的患者因严重的周围和自主神经病变而停止治疗。55例获得血液学缓解的患者中有9例(16%)出现NT-proBNP过高升高,并伴有心血管并发症,为化疗停药提供了依据。结论。器官恢复率低仍然是AL-A治疗中最具挑战性的问题。血液学反应深度(达到的CR)是取得临床效果的关键因素。获得的数据证实了BorCyDex方案对AL-A患者的高毒性。尽管AL-А治疗的进展与蛋白酶体抑制剂的使用有关,但这种疾病的治疗需要新的更有效的方法。
{"title":"Эффективность и токсичность индукционной терапии у пациентов с впервые диагностированным системным AL-амилоидозом: результаты проспективного одноцентрового клинического исследования","authors":"И. Г. Рехтина, Виктория Александровна Хышова, М. В. Соловьев, Л. П. Менделеева","doi":"10.21320/2500-2139-2023-16-2-166-173","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-2-166-173","url":null,"abstract":"Aim. To assess the outcomes of induction therapy in patients with newly diagnosed systemic AL Amyloidosis (AL-А).&#x0D; Materials &amp; Methods. The prospective single-center clinical study enrolled 60 patients (32 women and 28 men) with newly diagnosed systemic AL-A stage I/IIIA. The median age was 59 years (range 34–74 years). In 57 patients, BorСyDex (bortezomib, cyclophosphamide, dexamethasone) was used as first-line therapy. RCd regimen (lenalidomide, cyclophosphamide, dexamethasone) was administered to 3 patients. Patients with the lack of efficacy or pronounced toxicity (n = 24) received second-line induction therapy with lenalidomide or melphalan combined with dexamethasone. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was administered to 11 (18 %) patients.&#x0D; Results. Hematologic targeted response (complete remission [CR] and very good partial remission [VGPR]) to BorCyDex was achieved in 62 % of patients. As a result of all lines of induction therapy, including auto-HSCT, targeted response increased to 69 %, specifically in 7/51 (14 %) patients with stringent CR (sCR), 8/51 (16 %) patients with CR, and 20/51 (39 %) patients with VGPR. Renal response after BorCyDex was registered in 10/38 (26 %) patients, 6/31 (19 %) patients showed heart response, and in 4/5 (80 %) patients liver response was reported. All therapy lines with auto-HSCT led to organ response (in ≥ 1 organ) in 15/46 (32 %) patients. Clinical response was shown by all patients with achieved sCR, by 67 % of patients with CR, and 47 % with VGPR (p = 0.04). With lower hematologic response rates, no clinical improvement was observed. With follow-up duration of 36 months, the median disease-free survival (without signs of hematologic and clinical progression) was not achieved. The 3-year overall survival was 80 %. Mortality during induction therapy was 10 % (6 patients died, including 2 patients with COVID-19). The planned 6 courses of BorCyDex could be completed only in 13 (23 %) out of 55 patients. During the induction therapy using BorCyDex, 4 patients died. The treatment was discontinued in 7/55 (12 %) patients due to its inefficacy and in 22/55 (39 %) patients because of severe peripheral and autonomic polyneuropathy. Nine (16 %) out of 55 patients with the achieved hematologic response showed excessive NT-proBNP elevation, which was accompanied by cardiovascular complications and provided ground for chemotherapy withdrawal.&#x0D; Conclusion. Low organ recovery rate remains the most challenging issue for AL-A treatment. Hematologic response depth (achieved CR) is a critical factor in achieving clinical effect. The obtained data confirmed high toxicity of BorCyDex regimen in AL-A patients. Despite the advances in AL-А therapy which are associated with the use of proteasome inhibitors, treatment of this disease calls for new and more effective approaches.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"538 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135339917","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}
引用次数: 0
Экспрессия генов семейства WNT у больных множественной миеломой с различным ответом на противоопухолевую терапию 多发性骨髓瘤患者对抗肿瘤治疗有不同反应的WNT基因表达
Q4 Medicine Pub Date : 2023-03-03 DOI: 10.21320/2500-2139-2023-16-3-294-302
Натэлла Иосифовна Енукашвили, Л. А. Белик, И. И. Кострома, Н. Ю. Семенова, В. А. Балашова, Д. В. Барам, С. В. Грицаев, С. С. Бессмельцев, С. В. Сидоркевич, И. С. Мартынкевич
Aim. To compare the expression levels of the WNT family genes in mesenchymal stromal cells (MSC) of the bone marrow (BM) hematopoietic niche in multiple myeloma (MM) patients vs. healthy donors. Materials & Methods. The study enrolled 12 MM patients aged 49–71 years (the median age 61 years) after standard induction bortezomib therapy. The treatment efficacy was assessed in accordance with the criteria of International Myeloma Working Group (IMWG). Patients were stratified in groups with complete and partial response (CPR; group 1, n = 9) and no response (group 2, n = 3). Besides, a group of primary untreated patients was formed (n = 2). The control group included healthy donors of BM (n = 3). The levels of the WNT and CTNNB1 gene expression were assessed by real-time PCR on cDNA isolated from MSC. Results. In the group of 2 primary patients, two genes (WNT2B and WNT9B) considerably differed in the degree of expression. In non-responders (n = 3), the WNT2B expression could not be determined, whereas the WNT15 expression appeared to be increased. In group CPR (n = 9), mRNA level of the WNT5A gene increased after therapy, whereas the WNT3A gene expression returned to the normal level. The WNT7B gene transcription level did not differ in the control and comparison groups. In group CPR, a significant expression increase in the β-catenin-coding CTNNB1 gene was detected. Conclusion. The differences identified in the expression of the WNT2B, WNT9B, and CTNNB1 genes suggest the possibility of their use as prognostic molecular markers in MM.
的目标。比较多发性骨髓瘤(MM)患者骨髓(BM)造血生态位间充质基质细胞(MSC)中WNT家族基因的表达水平。 材料,方法。该研究招募了12名接受标准诱导硼替佐米治疗的MM患者,年龄49-71岁(中位年龄61岁)。按照国际骨髓瘤工作组(IMWG)的标准评估治疗效果。患者被分为完全缓解和部分缓解组(CPR;1组,n = 9)和无反应组(2组,n = 3),另设未治疗组(n = 2),对照组为健康BM供者(n = 3),采用MSC分离cDNA实时荧光定量PCR检测WNT和CTNNB1基因表达水平。结果。在2例原发患者中,两个基因(WNT2B和WNT9B)的表达程度存在显著差异。在无应答者(n = 3)中,无法确定WNT2B的表达,而WNT15的表达似乎有所增加。在CPR组(n = 9),治疗后WNT5A基因mRNA水平升高,而WNT3A基因表达恢复正常水平。WNT7B基因转录水平在对照组和对照组中没有差异。在CPR组中,β-连环蛋白编码基因CTNNB1的表达显著增加。 结论。WNT2B、WNT9B和CTNNB1基因表达的差异表明,它们有可能作为MM的预后分子标志物。
{"title":"Экспрессия генов семейства WNT у больных множественной миеломой с различным ответом на противоопухолевую терапию","authors":"Натэлла Иосифовна Енукашвили, Л. А. Белик, И. И. Кострома, Н. Ю. Семенова, В. А. Балашова, Д. В. Барам, С. В. Грицаев, С. С. Бессмельцев, С. В. Сидоркевич, И. С. Мартынкевич","doi":"10.21320/2500-2139-2023-16-3-294-302","DOIUrl":"https://doi.org/10.21320/2500-2139-2023-16-3-294-302","url":null,"abstract":"Aim. To compare the expression levels of the WNT family genes in mesenchymal stromal cells (MSC) of the bone marrow (BM) hematopoietic niche in multiple myeloma (MM) patients vs. healthy donors.&#x0D; Materials &amp; Methods. The study enrolled 12 MM patients aged 49–71 years (the median age 61 years) after standard induction bortezomib therapy. The treatment efficacy was assessed in accordance with the criteria of International Myeloma Working Group (IMWG). Patients were stratified in groups with complete and partial response (CPR; group 1, n = 9) and no response (group 2, n = 3). Besides, a group of primary untreated patients was formed (n = 2). The control group included healthy donors of BM (n = 3). The levels of the WNT and CTNNB1 gene expression were assessed by real-time PCR on cDNA isolated from MSC.&#x0D; Results. In the group of 2 primary patients, two genes (WNT2B and WNT9B) considerably differed in the degree of expression. In non-responders (n = 3), the WNT2B expression could not be determined, whereas the WNT15 expression appeared to be increased. In group CPR (n = 9), mRNA level of the WNT5A gene increased after therapy, whereas the WNT3A gene expression returned to the normal level. The WNT7B gene transcription level did not differ in the control and comparison groups. In group CPR, a significant expression increase in the β-catenin-coding CTNNB1 gene was detected.&#x0D; Conclusion. The differences identified in the expression of the WNT2B, WNT9B, and CTNNB1 genes suggest the possibility of their use as prognostic molecular markers in MM.","PeriodicalId":36905,"journal":{"name":"Klinicheskaya Onkogematologiya/Clinical Oncohematology","volume":"25 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135339918","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}
引用次数: 0
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Klinicheskaya Onkogematologiya/Clinical Oncohematology
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