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Clinical possibilities of flow cytometry in hodgkin’s lymphoma 流式细胞术在霍奇金淋巴瘤中的临床应用前景
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-70-77
F. M. Abbasbeyli, A. A. Fedenko, P. A. Zeynalova, R. F. Zibirov, V. N. Grinevich, T. Yu. Mushkarina, A. A. Melnikova, M. A. Vernyuk, L. Yu. Grivtsova
Hodgkin’s lymphoma (HL) is a unique lymphoma of b-cell origin, the tumor cells of which have lost the expression of main b-cell antigens. The standard immunophenotype of the tumor substrate, according to immunohistochemical studies, is characterized by the expression of such markers as CD15, CD30 and PAX-5, while tumor cells have a negative expression of CD3, CD19 and in most cases also CD20 and CD45 (or express this antigen rather weakly). The knowledge gained in recent years has increased the effectiveness of diagnosis, prognosis and treatment of LH. Flow cytometry, as a method of immunophenotyping in classical LH, was practically not used due to the difficulty of distinguishing single reed–sternberg–berezovsky tumor cells (RSB) and the tumor microenvironment (reactive background), which is very rich in cellular elements and is represented by T cells, B cells, eosinophils, histiocytes and plasma cells. However, in the recent past, several studies have successfully attempted to identify rsb cells using multiparameter flow cytometry during aspiration with a thin needle or biopsy of lymph node tissue to confirm or supplement immunohistochemical staining during primary diagnosis. Taking into account the very characteristic immunophenotype of RSB cells, the flow cytometry may become an additional diagnostic method of classical LH in the future. In this review, we summarize the data on the possibility of using the flow cytometry as an additional clinical diagnostic option in the primary diagnosis of classical LH.
霍奇金淋巴瘤(HL)是一种独特的起源于b细胞的淋巴瘤,其肿瘤细胞失去了主要b细胞抗原的表达。根据免疫组织化学研究,肿瘤底物的标准免疫表型以CD15、CD30、PAX-5等标记物的表达为特征,而肿瘤细胞CD3、CD19为阴性表达,多数情况下也为CD20、CD45(或表达该抗原较弱)。近年来获得的知识提高了LH的诊断、预后和治疗的有效性。流式细胞术作为经典LH的免疫分型方法,由于难以区分单个的reedsternberg - berezovsky肿瘤细胞(RSB)和以T细胞、B细胞、嗜酸性粒细胞、组织细胞和浆细胞为代表的细胞元素非常丰富的肿瘤微环境(反应性背景),因此实际上并未使用。然而,在最近的过去,一些研究成功地尝试在细针抽吸或淋巴结组织活检期间使用多参数流式细胞术鉴定rsb细胞,以确认或补充初级诊断期间的免疫组织化学染色。考虑到RSB细胞特有的免疫表型,流式细胞术在未来可能成为经典LH的附加诊断方法。在这篇综述中,我们总结了在经典LH的初步诊断中使用流式细胞术作为附加临床诊断选择的可能性的数据。
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引用次数: 0
Experience of 2<sup>nd</sup> line therapy with eltrombopag in patients with immune thrombocytopenia 2&lt; supit&gt;和&lt;/ supit&gt;在免疫性血小板减少症患者中使用埃曲波帕进行一线治疗
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-65-69
S. G. Zakharov, T. A. Mitina, R. V. Vardanyan, Z. R. Tekeeva, I. N. Kontievskiy, Yu. Yu. Chuksina, A. V. Zakharova
Background. Immune thrombocytopenia (ITP), or idiopathic thrombocytopenic purpura, is a hematological autoimmune disease characterized by bleeding and an isolated decrease in platelet count <100 × 10 9 / l. The decision to start treatment for ITP depends on several factors. The ITP treatment strategy is based on the clinical symptoms, with a focus on reducing the risk of severe bleeding and increasing platelet counts. Aim. To evaluate the efficacy of 2 nd line therapy with the thrombopoietin receptor agonist eltrombopag in patients with ITP. Materials and methods. 490 patients with ITP are under observation at the center for orphan diseases of M. F. Vladimirskiy Moscow Regional Research Clinical Institute. The present study included 186 patients with primary ITP after 1 st line glucocorticosteroid therapy. eltrombopag, a thrombopoietin receptor agonist, was prescribed as the 2 nd line of therapy. Results. The median platelet count prior to eltrombopag therapy in all patients was 27.5 × 10 9 / l. after eltrombopag therapy, a significant (by 490 %) increase in platelet levels (median 135 × 10 9 / l) and a complete response according to clinical recommendations were noted. Conclusion. Glucocorticosteroids (prednisolone, dexamethasone) remain the drugs of choice for the 1 st line of therapy. Treatment with drugs of this group in most cases allows achieving an optimal platelet level and preventing bleeding. In case of inefficiency, intolerance, occurrence of side effects, the appointment of thrombopoietin receptor agonists eltrombopag or romiplostim is recommended. therapy with eltrombopag at a dose of 50 mg daily for several weeks has been able to achieve an increase in platelet levels, correct hemorrhagic syndrome, reduce the number of side effects during first-line glucocorticosteroid therapy, and improve the patient’s quality of life.
背景。免疫性血小板减少症(ITP),或特发性血小板减少性紫癜,是一种血液学自身免疫性疾病,其特征是出血和孤立性血小板计数减少(100 × 10 / l)。ITP治疗策略以临床症状为基础,重点是减少严重出血的风险和增加血小板计数。的目标。评价血小板生成素受体激动剂埃曲巴格二线治疗ITP患者的疗效。材料和方法。莫斯科地区临床研究所的孤儿病中心正在观察490名ITP患者。本研究纳入186例经一线糖皮质激素治疗的原发性ITP患者。血栓生成素受体激动剂埃曲巴格被列为第二线治疗药物。结果。所有患者在接受依曲波包治疗前的中位血小板计数为27.5 × 109 / l,接受依曲波包治疗后,血小板水平显著(490%)增加(中位135 × 109 / l),并根据临床推荐达到完全缓解。结论。糖皮质激素(强的松龙、地塞米松)仍然是一线治疗的首选药物。在大多数情况下,使用该组药物治疗可以达到最佳血小板水平并防止出血。在无效、不耐受、出现副作用的情况下,推荐使用血小板生成素受体激动剂埃曲巴格或罗米普罗stim。使用每日50mg的伊曲波巴治疗数周,可以提高血小板水平,纠正出血性综合征,减少一线糖皮质激素治疗期间的副作用,并改善患者的生活质量。
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引用次数: 0
Follicular lymphoma in children and adolescents: clinical, diagnostic and therapeutic features 儿童和青少年滤泡性淋巴瘤:临床、诊断和治疗特点
Q4 Medicine Pub Date : 2023-09-11 DOI: 10.17650/1818-8346-2023-18-3-18-25
T. T. Valiev, A. S. Volkova, M. A. Postoykina, D. S. Abramov, A. R. Karibova, A. A. Odzharova, Yu. E. Ryabukhina, P. A. Zeynalova
Ffollicular lymphoma (FL) is one of the most common non-Hodgkin’s lymphomas in adults, while it is a diagnosis of exclusion in adolescents and children. Clinical manifestations of FL in children are represented by long-term asymptomatic lymphadenopathy, less commonly by extranodal areas involvement. treatment standards for FL in children have not been developed and may vary from observational tactics (with the radical resection of a single focus during a biopsy) to the use of radiation therapy and polychemotherapy. Pediatric type follicular lymphoma was first identified as a distinct variant in 2008 in the world Health organization classification of hematopoietic and lymphoid tissue tumors. Clinical, morphological (cytological type 3A), Immunohistochemical (absence of bcl2 expression in the center of the follicle) and cytogenetic (absence of t(14;18)(q32;q21)) features served as the reason for separation into an independent nosological variant. Despite the term “pediatric”, cases of pediatric type FL have been described in adults over 30 years of age. Most often, the disease is diagnosed in the early stages (I, II) and is characterized by a favorable prognosis. In children and adolescents, FL occurs not only of the pediatric type. we present a clinical case of a typical “adult” type FL (grade 1–2) in a 17-year-old patient. the cHop therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab resulted in a complete remission, which lasted more than 2.5 years.
滤泡性淋巴瘤(FL)是成人中最常见的非霍奇金淋巴瘤之一,而在青少年和儿童中是一种排除性的诊断。儿童FL的临床表现为长期无症状的淋巴结病变,较少累及结外区域。儿童滤泡性淋巴瘤的治疗标准尚未制定,可能从观察策略(在活检期间根治性切除单个病灶)到使用放射治疗和综合化疗有所不同。2008年,在世界卫生组织的造血和淋巴组织肿瘤分类中,儿科型滤泡性淋巴瘤首次被确定为一种不同的变体。临床、形态学(3A型细胞学)、免疫组化(卵泡中心缺乏bcl2表达)和细胞遗传学(缺乏t(14;18)(q32;q21))特征是分离成独立的病原学变异的原因。尽管有“儿科”一词,但在30岁以上的成年人中也有儿科型FL的病例。大多数情况下,该疾病在早期阶段(I, II)被诊断出来,其特点是预后良好。在儿童和青少年中,FL不仅发生在儿科类型。我们报告一个17岁患者的典型“成人”型FL(1-2级)的临床病例。cHop治疗(环磷酰胺、阿霉素、长春新碱和强的松龙)联合利妥昔单抗可完全缓解,持续时间超过2.5年。
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引用次数: 0
Immune thrombocytopenia in the aspect of multiple primary neoplasms 免疫性血小板减少症在多发性原发肿瘤中的作用
Q4 Medicine Pub Date : 2023-09-11 DOI: 10.17650/1818-8346-2023-18-3-44-49
R. V. Vardanyan, S. G. Zakharov, T. A. Mitina, P. A. Zeynalova, Yu. Yu. Chuksina, A. V. Zakharova
Multiple primary malignant neoplasms (MPMNs) is a complex process in which the development of 2 or more neoplasms simultaneously or after a certain interval is observed. MPMNs develop independently from each other within one or more organs. Many etiopathogenetic factors can cause MPMNs. Numerous studies have been conducted to study the effect of T-cell immunity on the development of this pathology. Today, there is a steady upward trend in the prevalence of mpmns, which, on the one hand, is due to more effective methods of early diagnosis, an increase in patient overall survival, and early antitumor therapy (chemotherapy, radiation therapy), on the other hand, this trend may be associated with pathology of T-regulatory cellular immunity. T-regulatory cells play a strategic role in the development of immune homeostasis, and their function is closely related to the occurrence of a wide range of pathologies, including autoimmune diseases and malignant neoplasms. The article presents a clinical case of a patient with a confirmed diagnosis: mpmn, immune thrombocytopenia (idiopathic thrombocytopenic purpura). On prednisolone therapy, remission was achieved for 2 metachronous tumors and a complete hematological response for immune thrombocytopenia was obtained. there were no signs of hemorrhagic syndrome and complications during prednisone therapy. It is planned to continue monitoring the patient for metachronous tumors by a hematologist, an oncologist at the place of residence, as well as at the center for orphan diseases of the Moscow Regional Research Clinical Institute named after M. F. Vladimirsky with control of platelets and general condition.
多发原发恶性肿瘤(Multiple primary malignant neoms, MPMNs)是2个或2个以上肿瘤同时发生或在一定时间间隔后发生的复杂过程。MPMNs在一个或多个器官内相互独立地发育。许多致病因素可引起MPMNs。已经进行了大量的研究来研究t细胞免疫对这种病理发展的影响。今天,mpmns的患病率呈稳步上升的趋势,这一方面是由于更有效的早期诊断方法,患者总生存率的增加,以及早期抗肿瘤治疗(化疗,放疗),另一方面,这一趋势可能与t调节细胞免疫的病理有关。t调节细胞在免疫稳态的发展中起着战略性的作用,其功能与包括自身免疫性疾病和恶性肿瘤在内的多种病理的发生密切相关。本文提出了一个临床病例的病人确诊:mpmn,免疫性血小板减少症(特发性血小板减少性紫癜)。在强的松龙治疗下,2例异时性肿瘤获得缓解,免疫血小板减少症获得完全的血液学反应。在强的松治疗期间没有出血综合征和并发症的迹象。计划继续由一名血液学家、一名肿瘤学家在其居住地以及莫斯科地区临床研究所孤儿病中心对患者进行异时性肿瘤监测,控制血小板和一般情况。
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引用次数: 0
Use of locally produced anti-CD19 CAR-T cells in the treatment of relapsed/refractory B-cell lymphomas in adults 使用局部生产的抗cd19 CAR-T细胞治疗成人复发/难治性b细胞淋巴瘤
Q4 Medicine Pub Date : 2023-09-11 DOI: 10.17650/1818-8346-2023-18-3-26-34
N. E. Konoplya, O. A. Kalenik, I. N. Severin, A. A. Savritskaya, N. M. Bobrova, T. M. Doroshenko, A. S. Portyanko
Background. Patients with B-cell lymphoma have an extremely unfavorable prognosis after relapse or in case of refractoriness to the first and consecutive lines of immunochemotherapy with the anti-CD19 CAR-T cells being the only therapeutic option to such patients. the manual preparation of anti-CD19 CAR-T lymphocytes was reproduced in the N. N. Alexandrov republican research and practical center for oncology and medical radiology (Minsk). Their safety was demonstrated. Aim. To estimate safety, tolerability and efficacy of the in-house CAR-T cells, including objective response rate, progression-free and overall survival. Materials and methods. The second generation anti-CD19 chimeric antigen receptor contained an anti-CD19 antibody scFv fragment, CD28 transmembrane domain, 4-1BB and CD3z signaling domains. the coding sequence was cloned into the lentiviral vector S4. The cell product was obtained by expansion of CD4- and CD8-positive lymphocytes populations with IL-7 and IL-15 after initial activation and lentiviral transduction with vector S4. CAR-T cells were infused into 8 patients with refractory forms of B-cell lymphoma after the preliminary lymphodepleting chemotherapy. Persistence of CAR-T cells was assessed by flow cytometry. therapeutic efficiency was assessed by positron emission tomography-computed tomography with 18 F-fluorodeoxyglucose. Results. Expansion of CAR-T cells with resulting b-cell aplasia was observed in all patients. the median of observation was 113 days (range 22–529 days). objective response rate was 100 %, complete remission was observed in 6 patients, partial response – in 1 patient. One patient died because of complications before the clinical response. Overall survival was 88 ± 12 %. cytokine release syndrome and neurotoxicity were not observed in 6 out of 8 patients despite a high tumor burden. Conclusion. Our study demonstrated efficiency and safety of the in-house CAR-T cells for the treatment of patients with refractory B-cell lymphomas.
背景。b细胞淋巴瘤患者在复发后或在第一次和连续免疫化疗难治性的情况下预后极其不利,抗cd19 CAR-T细胞是这类患者唯一的治疗选择。人工制备抗cd19 CAR-T淋巴细胞在N. N.亚历山德罗夫共和国肿瘤和医学放射学研究和实践中心(明斯克)进行了复制。他们的安全得到了证明。的目标。评估内部CAR-T细胞的安全性、耐受性和有效性,包括客观缓解率、无进展和总生存期。材料和方法。第二代抗cd19嵌合抗原受体含有抗cd19抗体scFv片段、CD28跨膜结构域、4-1BB和CD3z信号域。将编码序列克隆到慢病毒载体S4中。细胞产物是通过IL-7和IL-15初始激活后扩增CD4和cd8阳性淋巴细胞群,并用载体S4慢病毒转导获得的。CAR-T细胞被输注到8例难治性b细胞淋巴瘤患者的初步淋巴细胞耗尽化疗后。通过流式细胞术评估CAR-T细胞的持久性。采用正电子发射断层扫描- 18f -氟脱氧葡萄糖计算机断层扫描评估治疗效果。结果。在所有患者中都观察到CAR-T细胞扩增导致b细胞发育不全。观察时间中位数为113天(22-529天)。客观有效率为100%,完全缓解6例,部分缓解1例。1例患者在临床反应前因并发症死亡。总生存率为88±12%。8例患者中有6例没有观察到细胞因子释放综合征和神经毒性,尽管肿瘤负担很高。结论。我们的研究证明了内部CAR-T细胞治疗难治性b细胞淋巴瘤的有效性和安全性。
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引用次数: 0
An integrated treatment approach in patient with metastatic colorectal cancer and concomitant late cardiovascular complications of chemoradiotherapy for Hodgkin’s lymphoma. Clinical case 转移性结直肠癌伴晚期心血管并发症霍奇金淋巴瘤放化疗的综合治疗方法临床病例
Q4 Medicine Pub Date : 2023-09-11 DOI: 10.17650/1818-8346-2023-18-3-35-43
Yu. E. Ryabukhina, P. A. Zeynalova, A. A. Akhobekov, D. A. Chekini, E. K. Ibragimov, Z. M. Cheishvili, T. I. Kopaliani, V. E. Gruzdev, A. G. Zhukov, T. T. Valiev
The high efficacy of the currently used combined chemoradiotherapy for Hodgkin’s lymphoma not only significantly increased overall survival, but also made it possible for most patients to achieve the same quality of life as in a healthy population. at the same time, the problem of identifying late treatment complications, in particular cardiovascular the high efficacy of the currently used combined chemoradiotherapy for Hodgkin’s lymphoma not only significantly increased overall survival, but also made it possible for most patients to achieve the same quality of life as in a healthy population. at the same time, the problem of identifying late treatment complications, in particular cardiovascular diseases, remains an urgent problem, the timely diagnosis of which is an important task. the development of a second malignant neoplasm and the appointment of drug antitumor therapy with cardiotoxic agents necessitate a multidisciplinary approach. In the presented clinical observation, such tactics of patient management made it possible not only to timely identify late cardiovascular complications of Hodgkin’s lymphoma chemoradiotherapy, but also to conduct treatment for the second malignant disease with cardiotoxic agents with a positive antitumor effect.
目前使用的联合放化疗治疗霍奇金淋巴瘤的高效率不仅显著提高了总生存率,而且使大多数患者有可能达到与健康人群相同的生活质量。同时,发现治疗后期并发症的问题,特别是心血管疾病,目前使用的联合放化疗治疗霍奇金淋巴瘤的高效率不仅显著提高了总生存率,而且使大多数患者有可能达到与健康人群相同的生活质量。与此同时,识别治疗后期并发症,特别是心血管疾病,仍然是一个紧迫的问题,及时诊断是一项重要任务。第二种恶性肿瘤的发展和心脏毒性药物抗肿瘤治疗的任命需要多学科的方法。在本研究的临床观察中,这样的患者管理策略不仅可以及时发现霍奇金淋巴瘤放化疗的晚期心血管并发症,而且可以使用具有积极抗肿瘤作用的心脏毒性药物对第二次恶性疾病进行治疗。
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Oncogematologiya
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