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Toxicity of L-asparaginase drugs in acute lymphoblastic leukemia treatment l -天冬酰胺酶药物治疗急性淋巴细胞白血病的毒性研究
Q4 Medicine Pub Date : 2023-09-13 DOI: 10.17650/1818-8346-2023-18-3-134-139
T. T. Valiev
Currently no therapy of acute lymphoblastic leukemia is conceivable without L-asparaginase drugs, with its antileukemic effect by extracellular asparagine depletion, thus preventing its admission to leukemic cell. Besides high antitumor effect, L-asparaginase drugs have side and toxic effects, such as hypersensitivity reactions, thrombosis, pancreatitis / pancreatic necrosis, and hepatotoxicity. For L-asparaginase safety profile improvement a technology of pegylation was lay down and PEG-aspargase drug produced. This drug has less toxic effects and recommended as first-line therapy of acute lymphoblastic leukemia. Drug monitoring for assessment the effectiveness and toxicity of L-asparaginase is optimal. Such therapy individualization helps for L-asparaginase dose finding and decrease frequency and severity of side effects.
目前,没有l -天冬酰胺酶药物治疗急性淋巴细胞白血病是不可想象的,其抗白血病作用是通过细胞外天冬酰胺的消耗,从而防止其进入白血病细胞。l -天冬酰胺酶药物除具有较高的抗肿瘤作用外,还存在过敏反应、血栓形成、胰腺炎/胰腺坏死、肝毒性等毒副作用。为了提高l -天冬酰胺酶的安全性,提出了聚乙二醇化技术,并生产了聚乙二醇-天冬酰胺酶药物。该药毒性作用小,推荐作为急性淋巴细胞白血病的一线治疗药物。对l -天冬酰胺酶的有效性和毒性进行药物监测是最理想的。这种个体化治疗有助于发现l -天冬酰胺酶的剂量,减少副作用的发生频率和严重程度。
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引用次数: 0
Minor histocompatibility antigens represented in HLA-A*02:01 and their search strategies HLA-A*02:01所代表的次要组织相容性抗原及其搜索策略
Q4 Medicine Pub Date : 2023-09-13 DOI: 10.17650/1818-8346-2023-18-3-115-124
D. S. Romanyuk, A. M. Pilunov, G. A. Efimov, A. V. Bogolyubova, E. N. Parovichnikova
Minor histocompatibility antigens (MiHAs) are polymorphic peptides on the cell surface derived from self-proteins that are capable to induce an immune response during allogeneic hematopoietic stem cells transplantation. Their presentation occurs in the context of the certain major histocompatibility complex (HLA – human leucocyte antigen) alleles. One of the most common HLA alleles is HLA-A*02:01. Accordingly, for a significant number of donors and recipients pairs, it is possible to use the MiHAs presented in the HLA-A*02:01 as a target for relapsed leukemia therapy. This review discusses the main known MiHAs presented in the context of HLA-A*02:01, their characteristics and approaches used for identification. The described approaches may be used to search for new MiHAs for immunotherapy.
次要组织相容性抗原(MiHAs)是细胞表面由自身蛋白衍生的多态肽,能够在异基因造血干细胞移植过程中诱导免疫反应。它们的表现发生在某些主要组织相容性复合体(HLA -人类白细胞抗原)等位基因的背景下。HLA- a *02:01是最常见的HLA等位基因之一。因此,对于相当数量的供体和受体,可以使用HLA-A*02:01中提出的MiHAs作为复发性白血病治疗的靶点。本文综述了HLA-A*02:01中已知的主要miha、它们的特点和鉴定方法。所描述的方法可用于寻找用于免疫治疗的新的miha。
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引用次数: 0
Treatment of oncological and hematological diseases in HIV infection HIV感染后肿瘤和血液病的治疗
Q4 Medicine Pub Date : 2023-09-13 DOI: 10.17650/1818-8346-2023-18-3-125-133
S. V. Lushchevich, V. D. Litvinov
Oncological and hematological diseases associated with HIV infection continue to cause discussions among foreign and domestic researchers, clinicians, doctors, medical workers. The ongoing world globalization and modernization, environmental degradation have a detrimental effect on the health of citizens, which can be seen in virus mutations, high morbidity and a decrease in the social level in the Russian Federation and in the world. Oncological and hematological diseases associated with HIV infection are growing in the Russian Federation, but scientists do not stop at the results achieved, improving methods, treatment and therapy. As part of this study a statistical analysis of oncological and hematological diseases associated with HIV infection for 3 years (2019–2021) in Russia is carried out in order to trace the percentage of the medicine’s level, treatment’s effectiveness and deaths. A detailed analysis shows the decrease in deaths from HIV infection which pays attention the work of specialists in the Russian Federation. The purpose of this study is to identify a key method for the treatment of oncological and hematological diseases in HIV infection in Russia. The objective is to study the effectiveness of existing methods of treatment. Research methods – clinical, functional, microbiological and morphological.
与HIV感染相关的肿瘤和血液病继续引起国内外研究人员、临床医生、医生和医务工作者的讨论。正在进行的世界全球化和现代化、环境退化对公民的健康产生不利影响,这可以从俄罗斯联邦和全世界的病毒变异、高发病率和社会水平下降中看出。在俄罗斯联邦,与艾滋病毒感染有关的肿瘤和血液病正在增加,但科学家们并没有止步于取得的成果,不断改进方法、治疗和疗法。作为本研究的一部分,对俄罗斯与艾滋病毒感染相关的肿瘤和血液疾病进行了为期3年(2019-2021年)的统计分析,以追踪药物水平、治疗效果和死亡的百分比。一项详细的分析表明,感染艾滋病毒的死亡率有所下降,这引起了俄罗斯联邦专家的注意。本研究的目的是确定一个关键的方法治疗肿瘤和血液系统疾病在俄罗斯的艾滋病毒感染。目的是研究现有治疗方法的有效性。研究方法-临床,功能,微生物和形态学。
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引用次数: 0
Resolution of the Expert council “Unsolved problems of targeted therapy for paroxysmal nocturnal hemoglobinuria in Russia” 专家委员会关于“俄罗斯突发性夜间血红蛋白尿靶向治疗未解决问题”的决议
Q4 Medicine Pub Date : 2023-09-13 DOI: 10.17650/1818-8346-2023-18-3-140-144
A. D. Kulagin, E. A. Lukina, V. V. Ptushkin, M. P. Kostinov, E. G. Arshanskaya, T. N. Babaeva, T. I. Ksenzova, Z. T. Fidarova, M. V. Marchenko
On June 24, 2023, an Expert Council was held in St. Petersburg, during which leading experts in the field of hematology discussed current achievements and answered a number of unresolved issues of targeted therapy of paroxysmal nocturnal hemoglobinuria (APG) in order to further improve treatment results in Russia. During the Expert Council, the following aspects of targeted APG therapy were considered: • criteria for the suboptimal response of patients with APG to therapy with inhibitors of the 5th component of complement (C5); • efficacy and safety of the use of pegcetacoplan in APG in patients with insufficient efficacy of inhibitors of the C5 component of complement; • vaccination issues before starting therapy with complement inhibitors and the possibility of conducting treatment with pegcetacoplan at home.
2023年6月24日,专家委员会在圣彼得堡召开,血液学领域的顶尖专家讨论了目前的成果,并回答了一些尚未解决的阵发性夜间血红蛋白尿(APG)靶向治疗的问题,以进一步提高俄罗斯的治疗效果。在专家委员会期间,考虑了靶向APG治疗的以下方面:•APG患者对补体第5组分抑制剂(C5)治疗的次优反应标准;•补体C5成分抑制剂疗效不足的APG患者使用pegcetacoplan的有效性和安全性;•开始补体抑制剂治疗前的疫苗接种问题,以及在家中使用pegcetacoplan进行治疗的可能性。
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引用次数: 0
Risk factors for a differentiation syndrome in patients with acute promyelocytic leukemia 急性早幼粒细胞白血病患者分化证的危险因素
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-50-56
A. A. Semenova, V. V. Troitskaya, I. V. Galtseva, E. N. Parovichnikova
Differentiation syndrome (DS) is a severe complication of acute promyelocytic leukemia and its treatment, which is one of the causes of high early mortality. the similarity of clinical manifestations of DS and other complications that may develop during acute promyelocytic leukemia therapy makes it difficult to diagnose ds. at the same time, untimely initiation of DS therapy with glucocorticosteroids can lead to the patient’s death. The only generally accepted risk factor for ds is initial leukocytosis. Specific markers confirming ds have not yet been found. A number of studies show that in patients with diagnosed DS, the expression of CD56, CD54, CD2, CD15, CD13, markers of immature granulocytes, β2-integrins was more often found on blast cells. exposure to tretinoin increased the expression of chemokine receptors, chemokines, and cytokines by blast cells and vascular endothelium. The influence exerted by atypical promyelocytes, due to their biological characteristics, on the coagulation system suggests an association between hemostasis state and ds development. However, the value of the above markers as predictors or signs of DS still needs to be tested, especially when it comes to non-chemotherapeutic treatment of acute promyelocytic leukemia with arsenic trioxide.
分化证(DS)是急性早幼粒细胞白血病及其治疗的严重并发症,是早期死亡率高的原因之一。由于DS的临床表现与急性早幼粒细胞白血病治疗过程中可能出现的其他并发症的相似性,使得DS的诊断变得困难。同时,不及时地开始使用糖皮质激素进行退行性椎体变性治疗可能导致患者死亡。唯一被普遍接受的ds危险因素是初始白细胞增多。目前尚未发现证实ds的特定标记物。多项研究表明,在诊断为DS的患者中,CD56、CD54、CD2、CD15、CD13、未成熟粒细胞标志物、β2-整合素的表达更多见于胚细胞。接触维甲酸增加了母细胞和血管内皮中趋化因子受体、趋化因子和细胞因子的表达。非典型早幼粒细胞由于其生物学特性对凝血系统的影响表明,止血状态与ds的发展之间存在关联。然而,上述指标作为DS的预测指标或体征的价值仍有待检验,特别是在急性早幼粒细胞白血病非化疗应用三氧化二砷治疗时。
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引用次数: 0
Telomere length of various blood and bone marrow cells in patients with aplastic anemia 再生障碍性贫血患者各种血液和骨髓细胞的端粒长度
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-57-64
A. V. Luchkin, E. A. Mikhailova, I. V. Galtseva, Z. T. Fidarova, A. V. Abramova, Yu. O. Davydova, N. M. Kapranov, K. A. Nikiforova, S. M. Kulikov, E. N. Parovichnikova
Background. Aplastic anemia proceeds with bone marrow failure and is associated with immunological suppression of normal blood stem cells’ proliferation, which lead to bone marrow aplasia. autoimmune aggression and internal defects of blood stem cell that cause abnormal hematopoiesis are being actively studied. An important role in the pathogenesis of the aplastic anemia is played by instability of telomere length (TL). determination of the initial TL makes it possible to clearly differentiate between the aplastic anemia and dyskeratosis congenita. also, it helps to identify the group of patients with short telomeres for prediction of therapy response. Aim. To investigation the TL of various blood and bone marrow cells in patients with aplastic anemia before treatment. Materials and methods. The group of patients with aplastic anemia was investigated (n = 45). blood donors (n = 32) and bone marrow donors (n = 10) of different ages were included in the reference group. adult patients with dyskeratosis congenita (n = 5) were included in the comparison group. Relative and absolute tl was identified in peripheral blood and bone marrow mononuclear cells, monocytes, lymphocytes by flow-FISH technique (combination of flow cytometry and fluorescence in situ hybridization). Results. Relative and absolute TL was comparable in different blood and bone marrow cells in patients with aplastic anemia before treatment. TL in peripheral blood and bone marrow mononuclear cells wasn’t significantly differed in groups of patients with aplastic anemia and healthy donors. Telomeres in patients with dyskeratosis congenita were identified as “ultrashort” and were significantly shorter than in patients with aplastic anemia. Conclusion. Determination of TL in patients with aplastic anemia is modern examination method, which is a necessary step of differential diagnosis between aplastic anemia and dyskeratosis congenita, which is the disease from group of constitutional bone marrow aplasia. It is preferred to identify the TL in adult patients with aplastic anemia by the flow-FISH. It is necessary to investigate the TL to predict treatment response and to identify risks of developing adverse experiences, which include relapse and clonal evolution.
背景。再生障碍性贫血以骨髓衰竭为进展,并与正常造血干细胞增殖的免疫抑制有关,从而导致骨髓发育不全。自身免疫攻击和造血干细胞内部缺陷导致造血功能异常的研究正在积极进行。端粒长度不稳定在再生障碍性贫血的发病机制中起着重要作用。测定初始TL可以明确区分再生障碍性贫血和先天性角化不良。此外,它还有助于识别端粒短的患者群体,以预测治疗反应。的目标。目的探讨再生障碍性贫血患者治疗前各种血液及骨髓细胞的TL。材料和方法。对再生障碍性贫血患者组进行调查(n = 45)。参照组为不同年龄的献血者(n = 32)和骨髓献血者(n = 10)。成人先天性角化不良患者(n = 5)作为对照组。采用流式细胞术和荧光原位杂交相结合的flow- fish技术,对外周血和骨髓单核细胞、单核细胞、淋巴细胞进行相对和绝对tl鉴定。结果。治疗前再生障碍性贫血患者不同血液和骨髓细胞的相对和绝对TL具有可比性。再生障碍性贫血患者与健康供者外周血、骨髓单个核细胞TL差异无统计学意义。先天性角化不良患者的端粒被鉴定为“超短”,明显短于再生障碍性贫血患者。结论。再生障碍性贫血患者TL的测定是一种现代检查方法,是鉴别再生障碍性贫血与先天性角化不良(体质性骨髓发育不全组)的必要步骤。血流- fish是鉴别成人再生障碍性贫血患者TL的首选方法。有必要对TL进行研究,以预测治疗反应,并确定发生不良经历的风险,包括复发和克隆进化。
{"title":"Telomere length of various blood and bone marrow cells in patients with aplastic anemia","authors":"A. V. Luchkin, E. A. Mikhailova, I. V. Galtseva, Z. T. Fidarova, A. V. Abramova, Yu. O. Davydova, N. M. Kapranov, K. A. Nikiforova, S. M. Kulikov, E. N. Parovichnikova","doi":"10.17650/1818-8346-2023-18-3-57-64","DOIUrl":"https://doi.org/10.17650/1818-8346-2023-18-3-57-64","url":null,"abstract":"Background. Aplastic anemia proceeds with bone marrow failure and is associated with immunological suppression of normal blood stem cells’ proliferation, which lead to bone marrow aplasia. autoimmune aggression and internal defects of blood stem cell that cause abnormal hematopoiesis are being actively studied. An important role in the pathogenesis of the aplastic anemia is played by instability of telomere length (TL). determination of the initial TL makes it possible to clearly differentiate between the aplastic anemia and dyskeratosis congenita. also, it helps to identify the group of patients with short telomeres for prediction of therapy response. Aim. To investigation the TL of various blood and bone marrow cells in patients with aplastic anemia before treatment. Materials and methods. The group of patients with aplastic anemia was investigated (n = 45). blood donors (n = 32) and bone marrow donors (n = 10) of different ages were included in the reference group. adult patients with dyskeratosis congenita (n = 5) were included in the comparison group. Relative and absolute tl was identified in peripheral blood and bone marrow mononuclear cells, monocytes, lymphocytes by flow-FISH technique (combination of flow cytometry and fluorescence in situ hybridization). Results. Relative and absolute TL was comparable in different blood and bone marrow cells in patients with aplastic anemia before treatment. TL in peripheral blood and bone marrow mononuclear cells wasn’t significantly differed in groups of patients with aplastic anemia and healthy donors. Telomeres in patients with dyskeratosis congenita were identified as “ultrashort” and were significantly shorter than in patients with aplastic anemia. Conclusion. Determination of TL in patients with aplastic anemia is modern examination method, which is a necessary step of differential diagnosis between aplastic anemia and dyskeratosis congenita, which is the disease from group of constitutional bone marrow aplasia. It is preferred to identify the TL in adult patients with aplastic anemia by the flow-FISH. It is necessary to investigate the TL to predict treatment response and to identify risks of developing adverse experiences, which include relapse and clonal evolution.","PeriodicalId":37536,"journal":{"name":"Oncogematologiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135885705","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
Glomerular filtration rate dynamics in patients with diffuse large B-cell lymphoma during induction immunopolychemotherapy 弥漫性大b细胞淋巴瘤患者诱导免疫多化疗期间肾小球滤过率的动态变化
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-78-83
A. S. Nozdricheva, I. B. Lysenko, N. K. Guskova, M. A. Konovalchik, A. A. Maslov, E. V. Shalashnaya
Aim. To study the glomerular filtration rate (GFR) dynamics during induction immunopolychemotherapy (PCT) in patients with newly diagnosed diffuse large B-cell lymphoma. Materials and methods. The study included 39 patients with newly diagnosed diffuse large b-cell lymphoma who received specialized treatment in oncohematology department of national medical research centre for oncology (Rostov-on-Don). Patients underwent induction pct according to the R-CHOP (rituximab, doxorubicin, cyclophosphamide, vincristine, prednisolone) regimen with accompanying therapy (allopurinol). blood sampling was carried out at 0, 24, 48, 72, 120 hours and 21 days of the 1 st PCT cycle. GFR was calculated using the SKD-epicre formula (chronic Kidney disease epidemiology collaboration creatinine-based). statistical data processing was carried out using the IBM SPSS statistics 23 program. Results. According to the gfr level before the start of chemotherapy (0 hours), the patients were divided into two groups: group a with GFR > 90 ml / min / 1.73 m 2 and group b with GFR < 90 ml / min / 1.73 m 2 . In group a, there were no significant dynamic changes in the GFR level during PCT. Group B patients reacted more acutely to the administration of pct, which was manifested in an even greater decrease in the gfr level at 48 hours of PCT, and at 120 hours of PCT, the GFR approached the optimal values. on the 21 st day from the start of the 1 st pct course, the studied indicator returned to its initial values at 0 hour. further, the patients of these groups were divided into subgroups depending on the disease stage: group a consisted of 12 people with stages I–II and 15 people with stages III–IV. In group B, there were an equal number of patients with stages I–II and III–IV – 6 people. In group a, in patients with stages I–II and III–IV before the start of PCT (0 hours) and during PCT, there were no differences in the GFR level dynamics. In group B, patients with stages I-II and III–IV had similar GFR before the start of PCT, and during treatment, they reflected the previously noted general group trend in GFR level dynamics. Conclusion. The study found that in patients with initially low GFR level, a further, even more pronounced decrease in GFR during pct is observed. at the same time, the absence of significant differences in GFR level depending on disease stage allows us to conclude that the leading role is not so much the stage of the disease and tumor volume, but rather the initial functional status of the kidneys in the development of renal dysfunction in patients with diffuse large B-cell lymphoma during R-CHOP therapy.
的目标。探讨新诊断弥漫性大b细胞淋巴瘤患者诱导免疫多化疗(PCT)期间肾小球滤过率(GFR)的动态变化。材料和方法。本研究纳入39例新诊断的弥漫性大b细胞淋巴瘤患者,这些患者在国家肿瘤医学研究中心(顿河畔罗斯托夫)的肿瘤血液科接受了专门治疗。患者根据R-CHOP(利妥昔单抗、阿霉素、环磷酰胺、长春新碱、强的松龙)方案进行诱导pct,并辅以别嘌呤醇治疗。在第1个PCT周期的第0、24、48、72、120小时和21天进行血样采集。GFR采用SKD-epicre公式(慢性肾脏疾病流行病学合作组织以肌酐为基础)计算。统计数据处理采用IBM SPSS statistics 23程序。结果。根据化疗开始前(0小时)gfr水平将患者分为两组:a组gfr + gt;90 ml / min / 1.73 m2和b组GFR <90ml / min / 1.73 ma组患者在PCT期间GFR水平没有明显的动态变化,B组患者对PCT的反应更为剧烈,表现为GFR水平在PCT后48小时下降幅度更大,在PCT后120小时GFR接近最佳值。在第1个PCT课程开始后的第21天,所研究的指标在0小时恢复到其初始值。此外,这些组的患者根据疾病分期分为亚组:a组包括12名I-II期患者和15名III-IV期患者。在B组中,I-II期和III-IV期患者人数相同- 6人。在a组中,在PCT开始前(0小时)和PCT期间的I-II期和III-IV期患者,GFR水平动态无差异。在B组中,I-II期和III-IV期患者在PCT开始前的GFR相似,并且在治疗期间,它们反映了先前注意到的GFR水平动态的总体组趋势。结论。研究发现,在最初GFR水平较低的患者中,在pct期间观察到GFR进一步,甚至更明显的下降。同时,由于GFR水平在疾病分期上没有显著差异,我们可以得出结论,在弥漫性大b细胞淋巴瘤患者R-CHOP治疗期间肾功能障碍的发展中,主导作用与其说是疾病分期和肿瘤体积,不如说肾脏的初始功能状态。
{"title":"Glomerular filtration rate dynamics in patients with diffuse large B-cell lymphoma during induction immunopolychemotherapy","authors":"A. S. Nozdricheva, I. B. Lysenko, N. K. Guskova, M. A. Konovalchik, A. A. Maslov, E. V. Shalashnaya","doi":"10.17650/1818-8346-2023-18-3-78-83","DOIUrl":"https://doi.org/10.17650/1818-8346-2023-18-3-78-83","url":null,"abstract":"Aim. To study the glomerular filtration rate (GFR) dynamics during induction immunopolychemotherapy (PCT) in patients with newly diagnosed diffuse large B-cell lymphoma. Materials and methods. The study included 39 patients with newly diagnosed diffuse large b-cell lymphoma who received specialized treatment in oncohematology department of national medical research centre for oncology (Rostov-on-Don). Patients underwent induction pct according to the R-CHOP (rituximab, doxorubicin, cyclophosphamide, vincristine, prednisolone) regimen with accompanying therapy (allopurinol). blood sampling was carried out at 0, 24, 48, 72, 120 hours and 21 days of the 1 st PCT cycle. GFR was calculated using the SKD-epicre formula (chronic Kidney disease epidemiology collaboration creatinine-based). statistical data processing was carried out using the IBM SPSS statistics 23 program. Results. According to the gfr level before the start of chemotherapy (0 hours), the patients were divided into two groups: group a with GFR > 90 ml / min / 1.73 m 2 and group b with GFR < 90 ml / min / 1.73 m 2 . In group a, there were no significant dynamic changes in the GFR level during PCT. Group B patients reacted more acutely to the administration of pct, which was manifested in an even greater decrease in the gfr level at 48 hours of PCT, and at 120 hours of PCT, the GFR approached the optimal values. on the 21 st day from the start of the 1 st pct course, the studied indicator returned to its initial values at 0 hour. further, the patients of these groups were divided into subgroups depending on the disease stage: group a consisted of 12 people with stages I–II and 15 people with stages III–IV. In group B, there were an equal number of patients with stages I–II and III–IV – 6 people. In group a, in patients with stages I–II and III–IV before the start of PCT (0 hours) and during PCT, there were no differences in the GFR level dynamics. In group B, patients with stages I-II and III–IV had similar GFR before the start of PCT, and during treatment, they reflected the previously noted general group trend in GFR level dynamics. Conclusion. The study found that in patients with initially low GFR level, a further, even more pronounced decrease in GFR during pct is observed. at the same time, the absence of significant differences in GFR level depending on disease stage allows us to conclude that the leading role is not so much the stage of the disease and tumor volume, but rather the initial functional status of the kidneys in the development of renal dysfunction in patients with diffuse large B-cell lymphoma during R-CHOP therapy.","PeriodicalId":37536,"journal":{"name":"Oncogematologiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135885559","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
Genetic landscape of acute myeloid leukemias with leukocytosis 急性髓系白血病伴白细胞增多症的遗传景观
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-102-114
K. A. Pekhova, Yu. V. Sidorova, N. A. Severina, O. A. Glinshchikova, I. S. Fevraleva, B. V. Biderman, Yu. A. Chabaeva, S. M. Kulikov, I. A. Luk’yanova, A. I. Kashlakova, T. N. Obukhova, V. N. Dvirnyk, A. B. Sudarikov
Background. Tumor cell proliferation in acute myeloid leukemia (AML) may manifest with high leukocyte counts. In our work, we evaluate the association of high leukocyte counts with individual mutations, as well as their total contribution to the development of leukocytosis in AML. The results obtained should improve our understanding of pathogenic mechanisms leading to the leukocytosis in AML. Aim. To study the genetic landscape of AML with leukocytosis. Materials and methods. The laboratory data of 214 AML patients admitted to the National Medical Research Center for Hematology (Moscow) from 2010 to 2022 were retrospectively examined. Real-time PCR, capillary electrophoresis and NGS (next generation sequencing) methods were used to detect mutations of FLT3, NPM1, CEBPA, IDH1/2, DNMT3A, TET2 genes, and CBFB::MYH11, RUNX1::RUNX1T1 chimeric gene transcripts. Results. Mutations of the FLT3 gene (odds ratio 5.45; p < 0.0001), inv(16)/ CBFB::MYH11 (odds ratio 10.03; p = 0.0009) are most associated with leukocyte counts higher than 30 × 10 9 / L in the debut of AML. Translocation t(8;21) /RUNX1::RUNX1T1 and adverse cytogenetic aberrations, such as -5/del(5q); -7 / del(7q); -17 / abn(17p), complex and monosomic karyotype were significantly associated with leukocyte counts lower than 30 × 10 9 / L at the time of disease manifestation (p < 0.0001). In the group of patients with intermediate cytogenetic risk bearing only IDH1/2, DNMT3A , and TET2 gene mutations, leukocyte counts at AML debut were significantly lower, whereas the most pronounced leukocytosis was observed in patients with a combination of driver mutations with IDH1/2, DNMT3A , and TET 2 gene mutations or FLT3, NPM1 , and CEBPA gene mutations. Conclusion. In addition to the individual effect of certain genetic lesions and cytogenetic aberrations on the proliferative potential of tumor cells, there is a total contribution of various types of genetic events to the development of leukocytosis in AML. High leukocyte counts at the time of AML manifestation in patients with intermediate cytogenetic risk can serve as an indirect marker of the presence of a large number of genetic aberrations with a combination of IDH1/2, DNMT3A , and TET2 gene mutations or FLT3, NPM1 , and CEBPA gene mutations.
背景。急性髓性白血病(AML)的肿瘤细胞增殖可能表现为白细胞计数高。在我们的工作中,我们评估了高白细胞计数与个体突变的关系,以及它们对AML白细胞增多症发展的总体贡献。所获得的结果将提高我们对AML中导致白细胞增多的致病机制的理解。的目标。目的:研究AML伴白细胞增多症的遗传格局。材料和方法。回顾性分析2010 - 2022年在莫斯科国立血液学医学研究中心收治的214例AML患者的实验室资料。采用Real-time PCR、毛细管电泳和NGS(下一代测序)方法检测FLT3、NPM1、CEBPA、IDH1/2、DNMT3A、TET2基因突变以及CBFB::MYH11、RUNX1::RUNX1T1嵌合基因转录本。结果。FLT3基因突变(优势比5.45;p & lt;0.0001), inv(16)/ CBFB::MYH11(优势比10.03;p = 0.0009)与AML初发时白细胞计数高于30 × 10 9 / L最相关。易位t(8;21) /RUNX1::RUNX1T1和不良细胞遗传学畸变,如-5/del(5q);-7 / del(7q);-17 / abn(17p)、复核和单体核型与疾病表现时白细胞计数低于30 × 10 9 / L显著相关(p <0.0001)。在仅携带IDH1/2、DNMT3A和TET2基因突变的具有中等细胞遗传学风险的患者组中,AML首次发病时白细胞计数显著降低,而在IDH1/2、DNMT3A和TET2基因突变或FLT3、NPM1和CEBPA基因突变的驱动突变组合患者中观察到最明显的白细胞增多。结论。除了某些遗传病变和细胞遗传学畸变对肿瘤细胞增殖潜能的个体影响外,各种类型的遗传事件对AML中白细胞增多症的发展有总体贡献。中度细胞遗传风险患者AML表现时白细胞计数高,可作为存在大量遗传异常的间接标志,包括IDH1/2、DNMT3A、TET2基因突变或FLT3、NPM1、CEBPA基因突变。
{"title":"Genetic landscape of acute myeloid leukemias with leukocytosis","authors":"K. A. Pekhova, Yu. V. Sidorova, N. A. Severina, O. A. Glinshchikova, I. S. Fevraleva, B. V. Biderman, Yu. A. Chabaeva, S. M. Kulikov, I. A. Luk’yanova, A. I. Kashlakova, T. N. Obukhova, V. N. Dvirnyk, A. B. Sudarikov","doi":"10.17650/1818-8346-2023-18-3-102-114","DOIUrl":"https://doi.org/10.17650/1818-8346-2023-18-3-102-114","url":null,"abstract":"Background. Tumor cell proliferation in acute myeloid leukemia (AML) may manifest with high leukocyte counts. In our work, we evaluate the association of high leukocyte counts with individual mutations, as well as their total contribution to the development of leukocytosis in AML. The results obtained should improve our understanding of pathogenic mechanisms leading to the leukocytosis in AML. Aim. To study the genetic landscape of AML with leukocytosis. Materials and methods. The laboratory data of 214 AML patients admitted to the National Medical Research Center for Hematology (Moscow) from 2010 to 2022 were retrospectively examined. Real-time PCR, capillary electrophoresis and NGS (next generation sequencing) methods were used to detect mutations of FLT3, NPM1, CEBPA, IDH1/2, DNMT3A, TET2 genes, and CBFB::MYH11, RUNX1::RUNX1T1 chimeric gene transcripts. Results. Mutations of the FLT3 gene (odds ratio 5.45; p < 0.0001), inv(16)/ CBFB::MYH11 (odds ratio 10.03; p = 0.0009) are most associated with leukocyte counts higher than 30 × 10 9 / L in the debut of AML. Translocation t(8;21) /RUNX1::RUNX1T1 and adverse cytogenetic aberrations, such as -5/del(5q); -7 / del(7q); -17 / abn(17p), complex and monosomic karyotype were significantly associated with leukocyte counts lower than 30 × 10 9 / L at the time of disease manifestation (p < 0.0001). In the group of patients with intermediate cytogenetic risk bearing only IDH1/2, DNMT3A , and TET2 gene mutations, leukocyte counts at AML debut were significantly lower, whereas the most pronounced leukocytosis was observed in patients with a combination of driver mutations with IDH1/2, DNMT3A , and TET 2 gene mutations or FLT3, NPM1 , and CEBPA gene mutations. Conclusion. In addition to the individual effect of certain genetic lesions and cytogenetic aberrations on the proliferative potential of tumor cells, there is a total contribution of various types of genetic events to the development of leukocytosis in AML. High leukocyte counts at the time of AML manifestation in patients with intermediate cytogenetic risk can serve as an indirect marker of the presence of a large number of genetic aberrations with a combination of IDH1/2, DNMT3A , and TET2 gene mutations or FLT3, NPM1 , and CEBPA gene mutations.","PeriodicalId":37536,"journal":{"name":"Oncogematologiya","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135885706","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
Bone marrow composition features and possibilities of tumor involvement diagnosing in patients with classic Hodgkin’s lymphoma 经典霍奇金淋巴瘤患者骨髓组成特征及肿瘤累及诊断的可能性
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-84-91
F. M. Abbasbeyli, P. A. Zeynalova, M. A. Vernyuk, A. A. Fedenko, T. Yu. Mushkarina, A. A. Melnikova, V. Yu. Kovalskaya, L. Yu. Grivtsova
Background. Classical Hodgkin’s lymphoma is a B-cell lymphoproliferative disease, the tumor substrate of which is Berezovsky–Reed–Sternberg cells, characterized by CD30, PAX-5, CD15 expression and the absence of CD3, CD45. In some cases, tumor cells express CD20. modern anticancer therapy has increased the survival probability for most patients, not only with early but also with advanced stages of classical Hodgkin’s lymphoma. Such successes are mainly due to the distribution of patients into prognostic groups and the choice of an appropriate treatment regimen. tumor infiltration of the bone marrow suggests assigning patients to the advanced stages group, followed by the choice of an intensive therapy program. Aim. To determine the bone marrow involvement frequency according to positron emission tomography combined with computed tomography (PET/CT), with 18 F-fluorodeoxyglucose (FDG) and bone marrow trephine biopsy (bmtb), to compare the results obtained with primary tumor immunophenotype and bone marrow cellular composition, and to identify of prognostic risk factors. Materials and methods. The study included 107 patients with newly diagnosed classical Hodgkin’s lymphoma, who underwent a diagnostic examination at the moscow research institute of oncology named after P. A. Herzen – a branch of the National Medical Research Center for Radiology and the “Lapino” clinical Hospital from 2015 to 2022, followed by anticancer therapy and further follow-up. Morphology of the primary tumor biopsy specimen in all patients and immunohistochemical (IHC) study using a wide panel of monoclonal antibodies (CD15, CD30, CD3, CD45, CD20, PAX-5 anti-gens; in some cases epstein–barr virus proteins expression) in most cases were performed. All patients underwent a morphological and / or IHC study of BMTB and the majority underwent aspiration biopsy and PET/CT with 18 F-FDG. Results. The most common histological variant of classical Hodgkin’s lymphoma was nodular sclerosis (86.9 %). The majority of patients (51.4 %) were assigned to the advanced stage prognostic group. bone marrow tumor infiltration was statistically significantly more frequently diagnosed during PET/CT with 18 F-FDG compared with the results of the BMTB – in 27.1 % and 12.1 % of cases, respectively (p < 0.05). when comparing the results of both diagnostic methods, it was found that in 17.1 % of cases, bone marrow infiltration, detected during PET/CT, was not confirmed by IHC examination of the trephine biopsy. In addition, it was found that the majority of cases with CD20 +/± and CD15 +/± expression in the primary tumor were observed in the group of patients without bone marrow involvement. when assessing the cellular composition of bone marrow aspirates, it was revealed that in patients with bone marrow tumor infiltration, an increase in cellularity and megakaryocytes number along with a decrease in the plasma cells number is observed. Conclusion. The results suggest further study of bone marrow imm
背景。经典霍奇金淋巴瘤是一种b细胞淋巴增生性疾病,其肿瘤底物为Berezovsky-Reed-Sternberg细胞,以表达CD30、PAX-5、CD15而缺乏CD3、CD45为特征。在某些情况下,肿瘤细胞表达CD20。现代抗癌治疗提高了大多数患者的生存率,不仅是早期的,也包括晚期的经典霍奇金淋巴瘤。这样的成功主要是由于患者分布到预后组和选择适当的治疗方案。骨髓肿瘤浸润提示将患者分配到晚期组,然后选择强化治疗方案。的目标。根据正电子发射断层扫描联合计算机断层扫描(PET/CT)、18f -氟脱氧葡萄糖(FDG)和骨髓环磷石活检(bmtb)确定骨髓受累频率,将所得结果与原发性肿瘤免疫表型和骨髓细胞组成进行比较,并确定预后危险因素。材料和方法。该研究纳入了107名新诊断的经典霍奇金淋巴瘤患者,他们于2015年至2022年在莫斯科肿瘤研究所接受了诊断检查,该研究所是国家放射医学研究中心和“Lapino”临床医院的分支机构,以P. a . Herzen命名,随后接受了抗癌治疗和进一步随访。所有患者原发肿瘤活检标本的形态学和免疫组化(IHC)研究,使用广泛的单克隆抗体(CD15、CD30、CD3、CD45、CD20、PAX-5抗原);在一些病例中进行eb病毒蛋白表达,在大多数病例中进行。所有患者都接受了BMTB的形态学和/或免疫组化研究,大多数患者接受了18f - fdg的吸活检和PET/CT检查。结果。典型霍奇金淋巴瘤最常见的组织学变异是结节硬化(86.9%)。大多数患者(51.4%)被分配到晚期预后组。与BMTB -相比,18 F-FDG PET/CT诊断骨髓肿瘤浸润的频率分别为27.1%和12.1% (p <0.05)。对比两种诊断方法的结果发现,17.1%的病例在PET/CT检查中发现骨髓浸润,而在穿刺活检中免疫组化检查未证实。此外,我们发现原发肿瘤中CD20 +/±和CD15 +/±表达的病例多见于未累及骨髓的患者组。在评估骨髓抽吸液的细胞组成时,发现骨髓肿瘤浸润患者的细胞数量和巨核细胞数量增加,浆细胞数量减少。结论。结果提示进一步研究骨髓免疫形态特征,以确定预后因素和寻找新的治疗靶点。使用新的现代诊断方法对骨髓抽吸免疫生理特征进行更广泛的分析,最小残留疾病状态作为替代标记物似乎与确认抗肿瘤反应的深度相关且必要。原发性肿瘤免疫组化分析检测到CD20 +/±-和cd15 +/±- berezovsky - reed - sternberg细胞提示骨髓肿瘤浸润的可能性较低,但需要在大量临床和实验室材料上进一步分析。
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引用次数: 0
Clonal hematopoiesis and acute myeloid leukemia 克隆造血与急性髓性白血病
Q4 Medicine Pub Date : 2023-09-12 DOI: 10.17650/1818-8346-2023-18-3-92-101
A. I. Kashlakova, B. V. Biderman, E. N. Parovichnikova
During aging phenotypic changes in the hematopoietic system occur, and possible reason of these changes can be accumulation of gene mutations in hematopoietic stem cells or early blood progenitors. Although these mutations are mostly neutral, some may give hematopoietic stem cells and progenitor cells a proliferative advantage. In this case clonal hematopoiesis will arise, which is characterized by the formation of a genetically distinct subpopulation of blood cells. Clonal hematopoiesis may become a basis for the development of hematologic malignancies, such as acute myeloid leukemia. Clonal hematopoiesis associated genes which are most commonly mutated in acute myeloid leukemia patients are DNMT3A, TET2 and ASXL1. The prognostic significance of these gene mutations currently remains a subject of study.
在衰老过程中,造血系统发生表型变化,这些变化的可能原因可能是造血干细胞或早期血液祖细胞中基因突变的积累。虽然这些突变大多是中性的,但有些可能使造血干细胞和祖细胞具有增殖优势。在这种情况下,克隆造血将出现,其特点是形成一个遗传上不同的血细胞亚群。克隆造血可能成为恶性血液病发展的基础,如急性髓系白血病。在急性髓系白血病患者中最常发生突变的克隆性造血相关基因是DNMT3A、TET2和ASXL1。这些基因突变的预后意义目前仍是一个研究课题。
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引用次数: 0
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Oncogematologiya
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