Blood Reviews最新文献

英文中文

The intestinal flora: The key to unraveling heterogeneity in immune thrombocytopenia? 肠道菌群：揭示免疫性血小板减少症异质性的关键？

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2025-01-01 DOI: 10.1016/j.blre.2024.101252

Jente M. Schoenaker , Vivianne S. Nelson , Jannie G.E. Henderickx , Elisabeth M. Terveer , A.J. Gerard Jansen , Leendert Porcelijn , Tanja Netelenbos , Martin R. Schipperus , Rick Kapur

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by enhanced platelet destruction and impaired platelet production, due to a loss of immune tolerance that leads to targeting of platelets and megakaryocytes by glycoprotein-autoantibodies and/or cytotoxic T cells. There is a high degree of heterogeneity in ITP patients signified by unpredictable disease trajectories and treatment responses. Initial studies in humans have identified intestinal microbiota perturbance in ITP. Recently, gut microbial perturbance has been linked to other autoimmune diseases. Based on these findings, we hypothesize that intestinal microbiota may influence ITP pathophysiology through several mechanisms, including induction of platelet-autoantibody production, increasing complement-dependent platelet cytotoxicity, disturbing T cell homeostasis, impairing megakaryocyte function, and increasing platelet-desialylation and -clearance. The pathophysiological heterogeneity of ITP may, at least in part, be attributed to a perturbed intestinal microbiota. Therefore, a better understanding of intestinal microbiota in ITP may result in a more personalized therapeutic approach.

免疫性血小板减少症（ITP）是一种自身免疫性出血性疾病，其特征是血小板破坏增强和血小板产生受损，原因是免疫耐受性丧失，导致糖蛋白自身抗体和/或细胞毒性T细胞靶向血小板和巨核细胞。ITP患者具有高度的异质性，这意味着不可预测的疾病轨迹和治疗反应。对人类的初步研究已经确定了ITP的肠道微生物群紊乱。最近，肠道微生物紊乱与其他自身免疫性疾病有关。基于这些发现，我们假设肠道微生物群可能通过几种机制影响ITP的病理生理，包括诱导血小板自身抗体的产生，增加补体依赖性血小板细胞毒性，扰乱T细胞稳态，损害巨核细胞功能，增加血小板去脂化和清除。ITP的病理生理异质性可能至少部分归因于肠道微生物群的紊乱。因此，更好地了解ITP的肠道微生物群可能会导致更个性化的治疗方法。

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引用次数: 0

Impact of transcranial Doppler screening on stroke prevention in children and adolescents with sickle cell disease: A systematic review and meta-analysis 经颅多普勒筛查对儿童和青少年镰状细胞病卒中预防的影响：系统回顾和荟萃分析

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2025-01-01 DOI: 10.1016/j.blre.2024.101253

Danielle Guy , Robert Bagnall , Rebecca L. Morgan , Ifeoluwa Babatunde , Agathe Nevière , Gabriela Friedrich , Liga Bennetts , Omar Irfan , Isaac Odame

Background

Children with sickle cell disease (SCD) have increased stroke risk, identifiable by elevated velocities on transcranial Doppler (TCD). This review assessed the impact of TCD screening on stroke, mortality, quality of life and morbidity in children with SCD.

Methods

A systematic search of MEDLINE, PubMed, Cochrane libraries, and trial registries was conducted from inception to 28th February 2023. Randomised controlled trials (RCTs) and non-randomised studies (NRS) were included. A meta-analysis and narrative synthesis were performed.

Findings

Nine studies were included in the review. In one RCT, initiating chronic blood transfusion in children with abnormal TCD velocities reduced stroke risk by 92 %, while no deaths were reported. Pooled results from three NRS indicated TCD screening leads to four fewer strokes per 1000 patients annually. No studies analysing morbidity nor quality of life were identified.

Interpretation

TCD screening may decrease the risk of stroke in patients with SCD.

背景：镰状细胞病（SCD）患儿卒中风险增加，经颅多普勒（TCD）速度升高可识别。本综述评估了TCD筛查对SCD儿童卒中、死亡率、生活质量和发病率的影响。方法：系统检索MEDLINE、PubMed、Cochrane图书馆和试验注册库，检索时间为2023年2月28日。纳入随机对照试验（RCTs）和非随机研究（NRS）。进行meta分析和叙事综合。结果：本综述纳入了9项研究。在一项随机对照试验中，对TCD速度异常的儿童进行慢性输血可降低92%的卒中风险，同时无死亡报告。来自三个NRS的汇总结果表明，TCD筛查每年每1000名患者减少4例卒中。未发现分析发病率和生活质量的研究。解释：TCD筛查可降低SCD患者发生卒中的风险。

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引用次数: 0

Continuing progress in radioimmunotherapy for hematologic malignancies 恶性血液病放射免疫治疗的持续进展。

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2025-01-01 DOI: 10.1016/j.blre.2024.101250

Hiroki Goto , Yoshioki Shiraishi , Seiji Okada

Radioimmunotherapy (RIT) involves combining a cytotoxic radionuclide with an antibody (Ab) targeting a tumor antigen. Compared with conventional therapies, RIT improves the therapeutic efficacy of Ab and ameliorates toxicity. This comprehensive review describes the current advancements and future prospects in RIT for treating hematologic malignancies based on recent investigations. Although β-particle RITs targeting CD20 are effective with low toxicity in patients with relapsed/refractory indolent or transformed non-Hodgkin's lymphoma, these treatments have not gained popularity because of the increasing availability of new therapies. RIT using single-domain antibodies is expected to improve tumor penetrance and reduce radiation exposure to non-target organs. To enhance RIT efficacy, α-particle RIT and pretargeted radioimmunotherapy (PRIT) are currently being developed. Alpha-particle RIT demonstrates substantial antitumor activity and reduced bystander effects due to its high linear energy transfer and short particle range. PRIT may increase the tumor-to-whole body dose ratio.

放射免疫治疗（RIT）是将细胞毒性放射性核素与靶向肿瘤抗原的抗体（Ab）结合使用。与常规疗法相比，RIT提高了Ab的治疗效果，减轻了毒性。本文综合综述了RIT治疗血液系统恶性肿瘤的最新研究进展和未来前景。尽管靶向CD20的β颗粒RITs对复发/难治性惰性或转化性非霍奇金淋巴瘤患者有效且低毒，但由于新疗法的可用性不断增加，这些治疗尚未得到普及。使用单域抗体的RIT有望提高肿瘤外显率并减少对非靶器官的辐射暴露。为了提高RIT的疗效，α-颗粒RIT和预靶向放射免疫治疗（PRIT）正在研究中。α粒子RIT具有较高的线性能量传递和较短的粒子范围，具有较强的抗肿瘤活性和较低的旁观者效应。PRIT可增加肿瘤与全身的剂量比。

引用次数: 0

Point-of-care diagnostic test accuracy in children and adolescents with sickle cell disease: A systematic review and meta-analysis 儿童和青少年镰状细胞病的即时诊断测试准确性：一项系统回顾和荟萃分析

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2025-01-01 DOI: 10.1016/j.blre.2024.101243

Robert Bagnall , Danielle Guy , Rebecca L. Morgan , Ifeoluwa Babatunde , Agathe Nevière , Gabriela Friedrich , Liga Bennetts , Omar Irfan , Isaac Odame

Background

Detection of sickle cell disease (SCD) could be improved with greater use of point-of-care testing (POCT). This review assessed the accuracy of POCTs for SCD in children and adolescents.

Methods

We systematically searched EMBASE, PubMed, Cochrane libraries, registries and conference proceedings from inception to 28th February 2023. We included cross-sectional and case-control studies that tested for SCD using POCTs and reference tests in individuals aged 0–19. We conducted meta-analysis to assess sensitivity and specificity of individual POCTs.

Findings

The review included 31 studies overall, with 20 covering lateral flow immunoassays (LFIAs) and four covering micro-engineered electrophoresis. When detecting homozygous SCD, the pooled sensitivity and specificity of the included LFIAs and micro-engineered electrophoresis POCTs was 92 % or higher in all individual meta-analyses. Sensitivities and specificities were also nearly 100 % when detecting haemoglobin SC disease for these POCTs.

Interpretation

POCTs could be used to accurately diagnose SCD.

背景：镰状细胞病（SCD）的检测可以通过更多地使用即时检测（POCT）来改善。本综述评估了POCTs对儿童和青少年SCD的准确性。方法：我们系统地检索了EMBASE、PubMed、Cochrane图书馆、注册库和会议记录，检索时间从成立到2023年2月28日。我们纳入了在0-19岁的个体中使用POCTs和参考测试测试SCD的横断面和病例对照研究。我们进行了荟萃分析来评估个体poct的敏感性和特异性。结果：本综述共纳入31项研究，其中20项涉及侧流免疫测定（LFIAs）， 4项涉及微工程电泳。当检测纯合子SCD时，在所有个体荟萃分析中，纳入的LFIAs和微工程电泳POCTs的总灵敏度和特异性为92%或更高。在检测这些poct的血红蛋白SC疾病时，敏感性和特异性也接近100%。结论：POCTs可用于SCD的准确诊断。

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引用次数: 0

Neuro-toxicities of chemo- and immune-therapies in haematologic malignancies: from mechanism to management 血液恶性肿瘤化疗和免疫疗法的神经毒性：从机制到管理。

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2025-01-01 DOI: 10.1016/j.blre.2024.101254

David Kegyes , Vlad Moisoiu , Catalin Constantinescu , Alina Tanase , Gabriel Ghiaur , Hermann Einsele , Ciprian Tomuleasa , Hillard M. Lazarus , Robert Peter Gale

Chemo- and immune therapies administered to treat haematologic malignancies frequently cause neurologic injury. The adverse events range from mild cognitive impairment and headaches to severe conditions such as seizures, stroke and encephalitis. We performed a comprehensive literature review and report the types, mechanisms, management and prevention of neuro-toxicity resulting from these therapies in subjects who develop these toxic effects. Our paper will not discuss radiation therapy, as it has already been extensively reviewed by many authors. Our focus will be on recently developed anti-cancer drugs.

化疗和免疫疗法用于治疗恶性血液病经常引起神经损伤。不良事件的范围从轻微的认知障碍和头痛到严重的情况，如癫痫、中风和脑炎。我们进行了全面的文献综述，并报告了这些疗法在产生这些毒性作用的受试者中引起的神经毒性的类型、机制、管理和预防。我们的论文将不讨论放射治疗，因为它已经被许多作者广泛地回顾过。我们的重点将放在最近开发的抗癌药物上。

引用次数: 0

Host-directed therapies modulating innate immunity against infection in hematologic malignancies 宿主导向疗法调节先天免疫对抗血液恶性肿瘤感染。

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2024-12-13 DOI: 10.1016/j.blre.2024.101255

Qiong Wang , Kristján Hermannsson , Egill Másson , Peter Bergman , Guðmundur Hrafn Guðmundsson

Patients with hematologic malignancies (HM) are highly susceptible to bloodstream infection (BSI), particularly those undergoing treatments such as chemotherapy. A common and debilitating side effect of chemotherapy is oral and intestinal mucositis. These Patients are also at high risk of developing sepsis, which can arise from mucosal barrier injuries and significantly increases mortality in these patients. While conventional antibiotics are effective, their use can lead to antimicrobial resistance (AMR) and disrupt the gut microbiota (dysbiosis). In this review, we discuss utilizing host defense peptides (HDPs), key components of the innate immune system, and immune system inducers (ISIs) to maintain mucosal barrier integrity against infection, an underexplored host-directed therapy (HDT) approach to prevent BSI and sepsis. We advocate for the discovery of potent and safe ISIs for clinical use and call for further research into the mechanisms by which these ISIs induce HDPs and strengthen mucosal barriers.

恶性血液病（HM）患者极易发生血流感染（BSI），特别是那些正在接受化疗等治疗的患者。化疗的一个常见且使人衰弱的副作用是口腔和肠道粘膜炎。这些患者发生脓毒症的风险也很高，脓毒症可由粘膜屏障损伤引起，并显著增加这些患者的死亡率。虽然传统抗生素是有效的，但它们的使用可能导致抗菌素耐药性（AMR）并破坏肠道微生物群（生态失调）。在这篇综述中，我们讨论了利用宿主防御肽（HDPs）、先天免疫系统的关键成分和免疫系统诱导剂（ISIs）来维持粘膜屏障免受感染的完整性，这是一种未被充分探索的宿主定向治疗（HDT）方法来预防BSI和败血症。我们提倡发现有效和安全的ISIs用于临床应用，并呼吁进一步研究这些ISIs诱导hdp和加强粘膜屏障的机制。

引用次数: 0

Absolute and functional iron deficiency: Biomarkers, impact on immune system, and therapy 绝对性和功能性缺铁：生物标志物、对免疫系统的影响和治疗。

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2024-11-01 DOI: 10.1016/j.blre.2024.101227

Marianela Iriarte-Gahete , Laura Tarancon-Diez , Vanesa Garrido-Rodríguez , Manuel Leal , Yolanda María Pacheco

Iron is essential for numerous physiological processes and its deficiency often leads to anemia. Iron deficiency (ID) is a global problem, primarily affecting reproductive-age women and children, especially in developing countries. Diagnosis uses classical biomarkers like ferritin or transferrin saturation. Recent advancements include using soluble transferrin receptor (sTfR) or hepcidin for improved detection and classification of absolute and functional iron deficiencies, though mostly used in research. ID without anemia may present symptoms like asthenia and fatigue, even without relevant clinical consequences. ID impacts not only red-blood cells but also immune system cells, highlighting its importance in global health and immune-related comorbidities. Managing ID, requires addressing its cause and selecting appropriate iron supplementation. Various improved oral and intravenous products are available, but further research is needed to refine treatment strategies. This review updates on absolute and functional iron deficiencies, their relationships with the immune system and advancements in diagnosis and therapies.

铁是多种生理过程的必需元素，缺铁往往会导致贫血。缺铁（ID）是一个全球性问题，主要影响育龄妇女和儿童，尤其是在发展中国家。诊断使用传统的生物标志物，如铁蛋白或转铁蛋白饱和度。最近的进展包括使用可溶性转铁蛋白受体（sTfR）或血钙素来改进绝对性和功能性铁缺乏症的检测和分类，但主要用于研究。没有贫血的 ID 可能会出现气喘和疲劳等症状，甚至没有相关的临床后果。ID 不仅会影响红血细胞，还会影响免疫系统细胞，这凸显了它在全球健康和免疫相关合并症中的重要性。治疗 ID 需要解决其病因并选择适当的铁质补充剂。目前已有各种改良的口服和静脉注射产品，但还需要进一步的研究来完善治疗策略。本综述将介绍绝对性和功能性铁缺乏症的最新情况、它们与免疫系统的关系以及诊断和治疗方面的进展。

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引用次数: 0

Breaking down frailty: Assessing vulnerability in acute myeloid leukemia 打破虚弱：评估急性髓性白血病的脆弱性

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2024-11-01 DOI: 10.1016/j.blre.2024.101224

Lacey S. Williams , Teja Nagaradona , Prathik Nalamalapu , Catherine Lai

Acute myeloid leukemia (AML) is a disease primarily affecting older adults. However, not all patients at older ages are suitable for curative treatment with intensive chemotherapy due to “frailty” demonstrated by their functional status, physiologic reserve, and vulnerability to disease and treatment morbidity. Lack of consensus exists on how to select older, less fit patients most appropriate for standard intensive chemotherapy (IC), hypomethylating agents (HMA) with venetoclax, or less intensive regimens. A total of 37 studies of frailty assessments and composite indices in AML show heterogeneous results regarding the ability of frailty and Comprehensive Geriatric Assessment (CGA) measures to predict treatment outcomes. CGA, Geriatric 8 (G8) risk score, and hematopoietic cell transplant comorbidity index (HCT-CI) show association with prognosis, and should be validated in larger therapeutic trials. Studies of biomarkers, like albumin and C-reactive protein, and patient-reported outcomes demonstrate the potential to enhance information gained from rigorous geriatric assessment.

急性髓性白血病（AML）是一种主要影响老年人的疾病。然而，并非所有老年患者都适合接受强化化疗的根治性治疗，这是因为他们的 "虚弱 "表现在其功能状态、生理储备以及对疾病和治疗发病率的脆弱性。对于如何选择最适合接受标准强化化疗（IC）、低甲基化药物（HMA）与 Venetoclax 或较低强化方案的老年体弱患者，目前尚无共识。共有 37 项关于急性髓细胞白血病患者虚弱程度评估和综合指数的研究显示，虚弱程度和老年综合评估（CGA）指标预测治疗结果的能力存在差异。CGA、老年8（G8）风险评分和造血细胞移植综合指数（HCT-CI）显示与预后有关，应在更大规模的治疗试验中加以验证。对白蛋白和 C 反应蛋白等生物标志物以及患者报告结果的研究表明，通过严格的老年病学评估所获得的信息有可能得到加强。

引用次数: 0

Tailoring oral anticoagulant treatment in the era of multi-drug therapies for PAH and CTEPH 在 PAH 和 CTEPH 采用多种药物疗法的时代，调整口服抗凝剂的治疗方法。

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2024-11-01 DOI: 10.1016/j.blre.2024.101240

Jean Escal , Geraldine Poenou , Xavier Delavenne , Souad Bezzeghoud , Valentine Mismetti , Marc Humbert , David Montani , Laurent Bertoletti

The use of oral anticoagulants in the management of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) presents distinct therapeutic challenges and benefits. In PAH, the benefits of oral anticoagulation are uncertain, with studies yielding mixed results on their efficacy and safety. Conversely, oral anticoagulants are a cornerstone in the treatment of CTEPH, where their use is consistently recommended to prevent recurrent thromboembolic events. The choice between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) remains a significant clinical question, as each type presents advantages and potential drawbacks. Furthermore, drug-drug interactions (DDIs) with concomitant PAH and CTEPH treatments complicate anticoagulant management, necessitating careful consideration of individual patient regimens. This review examines the current evidence on oral anticoagulant use in PAH and CTEPH and discusses the implications of DDIs within a context of multi-drug treatments, including targeted drugs in PAH.

在治疗肺动脉高压（PAH）和慢性血栓栓塞性肺动脉高压（CTEPH）过程中使用口服抗凝剂既能带来不同的治疗挑战，也能带来不同的益处。在 PAH 中，口服抗凝药的益处尚不确定，有关其疗效和安全性的研究结果不一。相反，口服抗凝剂是治疗 CTEPH 的基石，在 CTEPH 的治疗中，一直建议使用口服抗凝剂来预防复发性血栓栓塞事件。在维生素 K 拮抗剂 (VKAs) 和直接口服抗凝剂 (DOAC) 之间做出选择仍然是一个重要的临床问题，因为每种药物都有其优点和潜在缺点。此外，同时接受 PAH 和 CTEPH 治疗时的药物间相互作用（DDIs）也使抗凝治疗变得更加复杂，因此有必要仔细考虑患者的个体治疗方案。本综述研究了 PAH 和 CTEPH 使用口服抗凝剂的现有证据，并讨论了多种药物治疗（包括 PAH 靶向药物）背景下 DDIs 的影响。

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引用次数: 0

Measurable residual disease (MRD)-testing in haematological cancers: A giant leap forward or sideways? 血液肿瘤中的可测量残留疾病（MRD）检测：大跃进还是走弯路？

IF 6.9 2区医学 Q1 HEMATOLOGY

Blood Reviews

Pub Date : 2024-11-01 DOI: 10.1016/j.blre.2024.101226

Qiujin Shen , Xiaowen Gong , Yahui Feng , Yu Hu , Tiantian Wang , Wen Yan , Wei Zhang , Saibing Qi , Robert Peter Gale , Junren Chen

Measurable residual disease (MRD)-testing is used in many haematological cancers to estimate relapse risk and to direct therapy. Sometimes MRD-test results are used for regulatory approval. However, some people including regulators wrongfully believe results of MRD-testing are highly accurate and of proven efficacy in directing therapy. We review MRD-testing technologies and evaluate the accuracy of MRD-testing for predicting relapse and the strength of evidence supporting efficacy of MRD-guided therapy. We show that at the individual level MRD-test results are often an inaccurate relapse predictor. Also, no convincing data indicate that increasing therapy-intensity based on a positive MRD-test reduces relapse risk or improves survival. We caution against adjusting therapy-intensity based solely on results of MRD-testing.

可测量残留病（MRD）检测用于许多血液癌症，以估计复发风险并指导治疗。有时，MRD 检测结果会被用于监管审批。然而，包括监管机构在内的一些人错误地认为 MRD 检测的结果非常准确，而且在指导治疗方面具有公认的疗效。我们回顾了 MRD 检测技术，并评估了 MRD 检测在预测复发方面的准确性以及支持 MRD 指导疗法疗效的证据力度。我们发现，就个体而言，MRD 检测结果往往不能准确预测复发。此外，没有令人信服的数据表明，根据MRD检测阳性结果增加治疗强度可降低复发风险或提高生存率。我们提醒不要仅根据 MRD 检测结果来调整治疗强度。

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