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[Rinsho ketsueki] The Japanese journal of clinical hematology最新文献

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[Advances in hemophilia treatment]. [血友病治疗进展]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.1087
Keiji Nogami

Advances in replacement therapy with clotting factor (F) VIII or FIX product have contributed greatly to reducing the incidence of hemophilic arthropathy and improving quality of life (QOL) in patients with hemophilia. However, frequent intravenous administration of clotting factor products, blood access, and development of alloantibodies (inhibitors) have been important issues. Clinical studies aimed at addressing these issues have been conducted in Japan as well, including a multicenter study to determine factors involved in inhibitor development. Drug development has also progressed: several clotting factor products with extended half-life and non-clotting factor therapies have been introduced in quick succession. Anti-FIX/FX bispecific antibody in particular has a long half-life when administered subcutaneously and controls bleeding in patients with hemophilia A. Anti-antithrombin therapy and anti-TFPI monoclonal antibody products that work by rebalancing coagulation have also been developed. In addition, gene therapy has been approved for adults in U.S. and Europe, where improved vectors and codon optimization have enabled protein expression up to the near-therapeutic hemostatic range. Recent significant developments in hemophilia treatment are expected to overcome long-standing problems and further improve QOL.

凝血因子 (F) VIII 或 FIX 产品替代疗法的进步极大地降低了血友病关节病的发病率,改善了血友病患者的生活质量(QOL)。然而,频繁静脉注射凝血因子产品、血液获取和异体抗体(抑制剂)的产生一直是个重要问题。日本也开展了旨在解决这些问题的临床研究,包括一项确定抑制剂产生因素的多中心研究。药物开发也取得了进展:几种延长半衰期的凝血因子产品和非凝血因子疗法相继问世。抗 FIX/FX 双特异性抗体的皮下注射半衰期较长,可控制 A 型血友病患者的出血,抗抗凝血酶疗法和抗 TFPI 单克隆抗体产品也已开发出来,它们通过重新平衡凝血发挥作用。此外,基因疗法已在美国和欧洲获准用于成人患者,通过改进载体和优化密码子,使蛋白质表达量接近治疗止血范围。血友病治疗领域的最新重大进展有望克服长期存在的问题,进一步改善患者的生活质量。
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引用次数: 0
[Practical guidance for CAR T-cell therapy in adults]. [成人 CAR T 细胞疗法实用指南]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.1155
Toshio Kitawaki

Chimeric antigen receptor (CAR) T-cell therapy is an innovative treatment for B-cell malignancies and multiple myeloma. CAR T-cell therapy is now approved in Japan and has become one of the essential therapeutic options for chemotherapy-resistant disease. It has many unique features that distinguish it from conventional chemotherapies, including the limitations imposed by the production of CAR-T cells from autologous T cells, and the limited availability and mandatory waiting period for treatment. Importantly, each patient has only one opportunity to receive CAR T-cell therapy. To achieve the maximum therapeutic benefit from CAR T-cell therapy, it is necessary to understand all aspects of CAR T-cell therapy, including factors that influence its efficacy. The design of the entire treatment sequence, including before and after CAR T-cell therapy, is also important to optimize clinical outcomes. In addition, since this treatment is only available at a limited number of facilities, effective coordination between local hospitals and treatment centers is also important. This educational session will focus on the practical aspects of CAR T-cell therapy in adults and will provide indispensable knowledge for providing CAR T-cell therapy to patients with B-cell lymphoma and multiple myeloma.

嵌合抗原受体(CAR)T 细胞疗法是一种治疗 B 细胞恶性肿瘤和多发性骨髓瘤的创新疗法。CAR T 细胞疗法现已在日本获得批准,并已成为化疗耐药疾病的基本治疗方案之一。CAR T 细胞疗法与传统化疗相比有许多独特之处,包括从自体 T 细胞中提取 CAR T 细胞所带来的限制,以及治疗的有限性和强制等待期。重要的是,每位患者只有一次接受 CAR T 细胞治疗的机会。要想从 CAR T 细胞疗法中获得最大的治疗效果,就必须了解 CAR T 细胞疗法的方方面面,包括影响其疗效的因素。整个治疗序列(包括 CAR T 细胞疗法前后)的设计对于优化临床结果也很重要。此外,由于这种疗法只在有限的几家机构提供,当地医院和治疗中心之间的有效协调也很重要。本讲座将重点介绍成人 CAR T 细胞疗法的实际操作,为 B 细胞淋巴瘤和多发性骨髓瘤患者提供 CAR T 细胞疗法不可或缺的知识。
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引用次数: 0
[Role of CAR-T in multiple myeloma and coordination between referring and treating centers]. [CAR-T在多发性骨髓瘤中的作用以及转诊中心和治疗中心之间的协调]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.1042
Satoshi Yoshihara

Immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 antibodies have been the three mainstays of myeloma treatment. B-cell maturation antigen (BCMA)-targeted immunotherapy, including chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibodies (BsAbs), is emerging as another important class of treatment. Two BCMA-targeting CAR-T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel, are approved in Japan, but only ide-cel is available for clinical use. Recently, a randomized phase III study comparing ide-cel with standard therapy in patients with refractory myeloma who had received 2 to 4 prior lines of therapy showed that ide-cel was superior in terms of both response rate and PFS. Based on these results, ide-cel was approved as a third-line therapy. The new availability of bispecific antibodies has also raised new clinical questions regarding how to use CAR-T and BsAbs for each patient, and in what order. Limited data have suggested that favorable responses can be achieved when BsAbs are administered after CAR-T, but responses are suboptimal when CAR-T is administered after BsAbs. Finally, it is important to note that coordination between referring centers and treating centers, including aspects such as timing of patient referral, bridging therapy, and long-term follow-up after CAR-T, is critical to optimization of CAR-T.

免疫调节药物(IMiDs)、蛋白酶体抑制剂(PIs)和抗CD38抗体一直是骨髓瘤治疗的三大支柱。B细胞成熟抗原(BCMA)靶向免疫疗法,包括嵌合抗原受体T细胞疗法(CAR-T)和双特异性抗体(BsAbs),正在成为另一种重要的治疗手段。日本已批准了两种以 BCMA 为靶点的 CAR-T 产品,即 idecabtagene vicleucel(ide-cel)和 ciltacabtagene autoleucel,但只有 ide-cel 可用于临床。最近,一项III期随机研究比较了ide-cel和标准疗法,结果显示,ide-cel在应答率和PFS方面均优于标准疗法。基于这些结果,ide-cel 被批准作为三线疗法。新出现的双特异性抗体也提出了新的临床问题,即如何为每位患者使用 CAR-T 和 BsAbs,以及使用的顺序。有限的数据表明,在 CAR-T 后使用 BsAbs 可以获得良好的反应,但在 BsAbs 后使用 CAR-T 则反应不佳。最后,需要注意的是,转诊中心和治疗中心之间的协调,包括患者转诊时机、桥接治疗和 CAR-T 后的长期随访等方面,对于优化 CAR-T 治疗至关重要。
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引用次数: 0
[Diffuse large B-cell lymphoma concurrent with Kaposi's sarcoma in the same lymph node in a human immunodeficiency virus-negative patient]. [一名人类免疫缺陷病毒阴性患者的弥漫大 B 细胞淋巴瘤与卡波西肉瘤同时出现在同一淋巴结中]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.74
Shiori Nakashima, Shin Ohara, Yui Imai, Hirofumi Nakano, Tomoyuki Uchida, Morihiro Inoue, Masao Hagihara

An 80-year-old Japanese man presented with systemic lymphadenopathy, including the para-aortic area and left inguinal nodes, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) and human herpesvirus (HHV) 8-positive/HIV-negative Kaposi's sarcoma (KS). Immunohistochemical examination revealed that the lymphoma cells were negative for HHV-8. The patient received combined chemotherapy with rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone for six cycles and achieved complete remission. In the literature, five cases of simultaneous appearance of malignant lymphoma and KS in the same lymph node have been reported, but DLBCL as a histological subtype has not yet been reported.

一名80岁的日本男子出现全身淋巴结病变,包括主动脉旁区域和左腹股沟结,被诊断为弥漫大B细胞淋巴瘤(DLBCL)和人类疱疹病毒(HHV)8阳性/HIV阴性卡波西肉瘤(KS)。免疫组化检查显示,淋巴瘤细胞的 HHV-8 阴性。患者接受了利妥昔单抗、吡拉比星、环磷酰胺、长春新碱和泼尼松龙联合化疗六个周期,并获得完全缓解。在文献中,有五例恶性淋巴瘤和 KS 同时出现在同一淋巴结的报道,但 DLBCL 作为一种组织学亚型尚未见报道。
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引用次数: 0
[Primary myelofibrosis with double mutation in U2AF1]. [原发性骨髓纤维化伴 U2AF1 双突变]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.30
Keiko Maeyama, Keiki Nagaharu, Kazuko Ino, Yuka Sugimoto, Isao Tawara, Keiki Kawakami

A 47-year-old woman presented with subcutaneous hemorrhage. Blood tests revealed leukoerythroblastosis, anemia, and thrombocytopenia. Bone marrow biopsy led to a diagnosis of primary myelofibrosis (aaDIPSS, DIPSS-plus: intermediate-II risk). JAK2, CALR, and MPL mutations were not detected in peripheral blood, but targeted sequencing of bone marrow specimens revealed a double mutation (Q157R, S34F) in U2AF1. Allo-PBSCT was performed using an HLA-matched related donor, and post-transplantation bone marrow examination showed complete donor chimerism on day 55. Two years after allogeneic transplantation, the patient remains relapse-free. Although U2AF1 gene abnormality is known as a poor prognostic factor in primary myelofibrosis, this patient had a favorable long-term prognosis due to prompt transplantation therapy. This case highlights the importance of detailed gene mutation analysis in patients with triple-negative MF.

一名 47 岁的妇女因皮下出血就诊。血液检查显示白细胞增多、贫血和血小板减少。骨髓活检诊断为原发性骨髓纤维化(aaDIPSS,DIPSS-plus:中II级风险)。外周血中未检测到 JAK2、CALR 和 MPL 突变,但骨髓标本的靶向测序发现 U2AF1 存在双突变(Q157R、S34F)。移植后骨髓检查显示,第55天时供体出现完全嵌合。异体移植两年后,患者仍未复发。尽管U2AF1基因异常是原发性骨髓纤维化的不良预后因素,但由于及时进行了移植治疗,该患者的长期预后良好。本病例强调了对三阴性骨髓纤维化患者进行详细基因突变分析的重要性。
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引用次数: 0
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.197
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引用次数: 0
[Pyogenic spondylitis after Corynebacterium striatum blood stream infection following allogeneic hematopoietic stem cell transplantation for malignant lymphoma]. [因恶性淋巴瘤接受异体造血干细胞移植后,因纹状体科里奈杆菌血流感染引发化脓性脊柱炎]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.243
Takumi Nishikawa, Masuho Saburi, Kentaro Nagamatsu, Keiichi Uraisami, Hiroyuki Takata, Yasuhiko Miyazaki, Eiichi Ohtsuka

Patient 1 was a 70-year-old woman with refractory diffuse large B-cell lymphoma who received allogeneic peripheral blood stem cell transplantation from an HLA-haploidentical related donor. Upper back pain appeared on day63, and Th8-Th9 pyogenic spondylitis was diagnosed based on magnetic resonance imaging (MRI). Blood culture on day14 identified Corynebacterium striatum as the causative bacteria of blood stream infection (BSI). The pyogenic spondylitis resolved after treatment with daptomycin for 2 months. Patient 2 was a 65-year-old man with relapsed angioimmunoblastic T-cell lymphoma who received bone marrow transplantation from an HLA-DR single-antigen-mismatched unrelated donor. Lower back pain appeared on day30, and L4-L5 pyogenic spondylitis was diagnosed based on MRI. Blood culture was negative. Daptomycin and clindamycin were selected for treatment based on the drug susceptibility of bacteria that had caused pre-engraftment BSI (Escherichia coli on day3 and Corynebacterium striatum on day9), and the pyogenic spondylitis resolved after 6 months of this treatment. Pyogenic spondylitis should be considered in the differential diagnosis of back pain accompanied by BSI before engraftment in allogeneic hematopoietic stem cell transplant recipients.

患者1是一名70岁的女性,患有难治性弥漫大B细胞淋巴瘤,接受了HLA同种异体干细胞移植。第63天出现上背痛,根据磁共振成像(MRI)诊断为Th8-Th9化脓性脊柱炎。第 14 天的血液培养发现,纹状体棒状杆菌是血流感染(BSI)的致病菌。使用达托霉素治疗 2 个月后,化脓性脊柱炎痊愈。患者2是一名65岁的男性,患有复发性血管免疫母细胞T细胞淋巴瘤,接受了HLA-DR单抗原不匹配非亲属供者的骨髓移植。第30天出现下背部疼痛,根据核磁共振成像诊断为L4-L5化脓性脊柱炎。血液培养呈阴性。根据引起移植前 BSI 的细菌(第 3 天为大肠埃希菌,第 9 天为纹状杆菌)对药物的敏感性,选择了达托霉素和林可霉素进行治疗,经过 6 个月的治疗,化脓性脊柱炎得到缓解。异体造血干细胞移植受者在移植前出现背痛并伴有BSI时,应将化脓性脊柱炎考虑在鉴别诊断中。
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引用次数: 0
[Infection stress and a driver mutation interact to promote transformation to hematological malignancies]. [感染压力和驱动突变相互作用,促进向血液恶性肿瘤的转化]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.702
Goro Sashida

Myelodysplastic syndrome (MDS) is a refractory cancer that arises from hematopoietic stem cells and predominantly affects elderly adults. In addition to driver gene mutations, which are also found in clonal hematopoiesis in healthy elderly people, systemic inflammation caused by infection or collagen disease has long been known as an extracellular factor in the pathogenesis of MDS. Wild-type HSCs have an "innate immune memory" that functions in response to infection and inflammatory stress, and my colleagues and I used an infection stress model to demonstrate that the innate immune response by the TLR-TRIF-PLK-ELF1 pathway is similarly critical in impairment of hematopoiesis and dysregulation of chromatin in MDS stem cells. This revealed that not only are MDS stem cells expanded by the TRAF6-NF-kB pathway, the innate immune response is also involved in generating MDS stem cells. In this review, I will present research findings related to "innate immune memory," one of the pathogenic mechanisms of blood cancer, and discuss future directions for basic pathological research and potential therapeutic development.

骨髓增生异常综合征(MDS)是一种由造血干细胞引起的难治性癌症,主要影响老年人。除了在健康老年人的克隆性造血中也发现的驱动基因突变外,感染或胶原病引起的全身炎症早已被认为是MDS发病机制中的细胞外因素。野生型造血干细胞具有 "先天性免疫记忆",可对感染和炎症应激做出反应。我和我的同事利用感染应激模型证明,TLR-TRIF-PLK-ELF1途径的先天性免疫反应同样是MDS干细胞造血功能受损和染色质失调的关键。这揭示了MDS干细胞不仅通过TRAF6-NF-kB途径扩增,先天性免疫反应也参与了MDS干细胞的生成。在这篇综述中,我将介绍与血癌致病机制之一的 "先天免疫记忆 "有关的研究成果,并讨论基础病理研究和潜在治疗开发的未来方向。
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引用次数: 0
[Recent findings and advances in treatment of myeloproliferative neoplasms]. [骨髓增生性肿瘤治疗的最新发现和进展]。
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.375
Yuka Sugimoto

Many novel agents have been developed for BCR::ABL1-negaive myeloproliferative neoplasms (MPN), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Some of these agents not only achieve hematologic complete response, reduce spleen size, and alleviate constitutional symptoms, but also induce molecular response, which means that they reduce the allele burden of driver gene mutations. These agents also prevent and alleviate fibrosis in bone marrow, which reduces the incidence of thrombotic events and disease progression and might improve prognosis. This article discusses the latest findings and promising treatments, including ongoing clinical trials, in PV, ET, and PMF.

针对BCR::ABL1-negaive骨髓增殖性肿瘤(MPN),即真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF),已开发出许多新型药物。其中一些药物不仅能获得血液学完全应答、缩小脾脏体积和缓解体征,还能诱导分子应答,即减少驱动基因突变的等位基因负荷。这些药物还能预防和缓解骨髓纤维化,从而降低血栓事件和疾病进展的发生率,并可能改善预后。本文讨论了针对骨髓增生性白血病、骨髓移植和骨髓纤维化的最新发现和有前景的治疗方法,包括正在进行的临床试验。
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引用次数: 0
Pub Date : 2024-01-01 DOI: 10.11406/rinketsu.65.439
{"title":"","authors":"","doi":"10.11406/rinketsu.65.439","DOIUrl":"https://doi.org/10.11406/rinketsu.65.439","url":null,"abstract":"","PeriodicalId":93844,"journal":{"name":"[Rinsho ketsueki] The Japanese journal of clinical hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201480","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
期刊
[Rinsho ketsueki] The Japanese journal of clinical hematology
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