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Let's YAP about ITP. 让我们一起 YAP ITP。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026571
Rick Kapur, John W Semple
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引用次数: 0
Approaching a therapeutic inflection point for FLT3-mutated AML. 接近FLT3突变型急性髓细胞白血病的治疗拐点。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024024248
Alexander E Perl

Combining FLT3 inhibitors with intensive chemotherapy and transplant has substantially improved AML outcomes, prompting a recent re-evaluation of FLT3-ITD's historically negative prognostic effect. Treatment approaches may soon undergo major changes as emerging data suggest maximal intensity does not benefit all patients and MRD potentially can guide several treatment choices. Finally, recent data also suggest FLT3 inhibitors could transform outcomes in patients unsuitable for intensive therapy. If confirmed, this has important implications for fit patients and could revolutionize the treatment paradigm.

将FLT3抑制剂与强化化疗和移植相结合大大改善了急性髓细胞性白血病的预后,促使人们最近重新评估FLT3-ITD历来对预后的负面影响。治疗方法可能很快会发生重大变化,因为新出现的数据表明,最大强度化疗并不能使所有患者获益,MRD 有可能指导多种治疗选择。最后,最近的数据还表明,FLT3 抑制剂可以改变不适合接受强化治疗的患者的预后。如果得到证实,这将对适合治疗的患者产生重要影响,并可能彻底改变治疗模式。
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引用次数: 0
Building the Future Management of Follicular Lymphoma with T-Cell-Redirecting Strategies. 用T细胞定向策略打造滤泡性淋巴瘤的未来疗法
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024025699
Gloria Iacoboni, Franck Morschhauser

Follicular lymphoma (FL) usually requires multiple lines of therapy and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T-cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.

滤泡性淋巴瘤(FL)通常需要多线治疗,而传统的化学免疫疗法在很大程度上仍无法控制病情。最近获批用于复发/难治性治疗的几种T细胞重定向策略有望改善FL的治疗效果并改变治疗算法。本综述将重点讨论嵌合抗原受体T细胞和双特异性抗体在FL中的作用,并特别关注测序方法和未来发展方向。
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引用次数: 0
Ruxolitinib REACHes FOR children with GVHD. Ruxolitinib可用于治疗GVHD患儿。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026120
Tomomi Toubai
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引用次数: 0
How I approach the treatment of thrombotic complications in patients with myeloproliferative neoplasms. 我如何治疗骨髓增生性肿瘤患者的血栓并发症。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024025627
Alexandre Guy, Pierre-Emmanuel Morange, Chloé James

Arterial and venous thromboses are the most significant complications in patients with myeloproliferative neoplasms (MPN), with the primary treatment goal being thrombotic risk reduction. In MPN with no history of thrombosis, primary prevention mainly involves the use of aspirin and cytoreduction is added in high-risk patients. However, thrombotic complications can unveil an MPN in approximately 20% of cases, necessitating the initiation of both antithrombotic therapy for the thrombosis and cytoreductive treatment for the MPN. The duration of anticoagulant therapy following an initial venous thromboembolic event (VTE) is subject to discussion. Furthermore, the occurrence of a thrombotic complication in patients with a known diagnosis of MPN prompts a reconsideration of both antithrombotic and hematological management. This review employs case-based discussions to explore the management of thrombotic complications in MPN patients. It addresses the nature and duration of antithrombotic treatments, as well as the approach to cytoreduction. Special attention is given to the place of direct oral anticoagulants and to the management of MPN patients with splanchnic vein thrombosis, which is disproportionately common in this group.

动脉和静脉血栓是骨髓增生性肿瘤(MPN)患者最主要的并发症,治疗的首要目标是降低血栓风险。对于无血栓形成病史的骨髓增生性肿瘤患者,一级预防主要包括使用阿司匹林,高危患者则需加用细胞减灭术。然而,约有 20% 的病例会出现血栓并发症,这就需要同时对血栓进行抗血栓治疗和对 MPN 进行细胞减灭术治疗。初次静脉血栓栓塞事件(VTE)后抗凝治疗的持续时间有待讨论。此外,已确诊为 MPN 的患者出现血栓并发症时,需要重新考虑抗血栓治疗和血液学治疗。本综述以病例讨论为基础,探讨如何处理 MPN 患者的血栓并发症。它探讨了抗血栓治疗的性质和持续时间,以及细胞减少的方法。其中特别关注了直接口服抗凝剂的地位,以及对患有脾静脉血栓的 MPN 患者的管理,因为脾静脉血栓在这一群体中尤为常见。
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引用次数: 0
Oxidative hemolysis due to phenazopyridine in the absence of G6PD deficiency. 在没有 G6PD 缺乏症的情况下,苯并吡啶会导致氧化溶血。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026349
Arielle L Langer
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引用次数: 0
Imetelstat: A new addition to the Therapeutic Landscape of Lower-Risk MDS. 伊美司他低风险 MDS 治疗领域的新成员。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024025702
Yasmin Abaza, Amy E DeZern

Anemia is the most prevalent cytopenia in lower-risk myelodysplastic neoplasms (LR-MDS). There is a paucity of drugs for red blood cell transfusion dependence (RBC-TD) and erythropoiesis-stimulating agents (ESAs) are the mainstay of therapy in many centers. Imetelstat, an oligonucleotide telomerase inhibitor, was recently approved for RBC-TD LR-MDS adults who are ineligible or failed prior ESA therapy. While not yet approved worldwide, here, we spotlight the current data for imetelstat and where it may fit in the therapeutic landscape of LR-MDS.

贫血是低风险骨髓增生异常肿瘤(LR-MDS)中最常见的全血细胞减少症。目前治疗红细胞输注依赖症(RBC-TD)的药物很少,红细胞生成刺激剂(ESAs)是许多中心的主要治疗手段。Imetelstat是一种寡核苷酸端粒酶抑制剂,最近被批准用于治疗不符合条件或既往ESA治疗失败的RBC-TD LR-MDS成人患者。虽然该药物尚未在全球范围内获得批准,但我们将在此重点介绍伊美司他的当前数据以及它在 LR-MDS 治疗中的应用前景。
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引用次数: 0
Ferroptosis regulates hemolysis in stored murine and human red blood cells. 铁蛋白沉积调节贮存的小鼠和人类红细胞溶血。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026109
Angelo D'Alessandro, Gregory R Keele, Ariel M Hay, Travis Nemkov, Eric J Earley, Daniel Stephenson, Matthew Vincent, Xutao Deng, Mars Stone, Monika Dzieciatkowska, Kirk C Hansen, Steven H Kleinman, Steven L Spitalnik, Nareg H Roubinian, Philip J Norris, Michael P Busch, Grier P Page, Brent Stockwell, Gary A Churchill, James C Zimring

Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for post-transfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid Quantitative Trait Loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase Steap3, a transcriptional target to p53. Steap3 regulated post-transfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation and in vitro hemolysis in 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (FADS1/2, EPHX2, LPCAT3, SLC22A16, G6PD, ELOVL, PLA2G6) associated with lower levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.

红细胞(RBC)的新陈代谢调节着体内和血库中衰老过程中的溶血。然而,人们对红细胞代谢异质性和群体规模的血管外溶血的遗传基础还不完全了解。基于 8 个遗传多样性极高的创始品系的培育,杰克逊实验室的多样性外源种群可以像基于群体的研究一样捕捉遗传异质性的影响。对来自 350 只近交系小鼠的新鲜或保存 7 天的红细胞进行了输血后恢复测试,以及代谢组学和脂质组学分析。代谢物和脂质定量性状位点(QTL)绘制了超过 400 个基因-代谢物关联图,我们将其整理成一个在线互动门户。与红细胞储藏有关,我们在 1 号染色体上发现了一个 QTL 热区,它映射在铁还原酶 Steap3 的编码区域,而 Steap3 是 p53 的转录靶标。Steap3调控输血后的恢复,有助于类似铁变态反应的脂质过氧化过程,这一点通过对小鼠的遗传操作得到了验证。STEAP3多态性与受血者流行病学和献血者评估研究(Repipient Epidemiology and Donor Evaluation Study)中 13,091 名献血者的红细胞铁含量、脂质过氧化和体外溶血有关。人类 QTL 分析确定了一个与较低水平氧化脂质相关的基因产品网络(FADS1/2、EPHX2、LPCAT3、SLC22A16、G6PD、ELOVL、PLA2G6)。这些多态性普遍存在于非洲裔供体中,并与 Steap3 或 p53 的溶血相关多态性的等位基因频率有关。这些基因变异还与静脉输血数据库中数千名单单位输血受血者的血红蛋白增量较低有关。
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引用次数: 0
Location, location, location: EMD in MM. 位置、位置、位置:MM 的 EMD。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026430
Madhav V Dhodapkar
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引用次数: 0
Heparin versus normal saline locking for prevention of occlusion, catheter-related infections and thrombosis in central venous catheter in adults: Overview of systematic reviews. 肝素与生理盐水锁闭预防成人中心静脉导管闭塞、导管相关感染和血栓形成:系统综述。
IF 21 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-11-01 Epub Date: 2022-06-10 DOI: 10.1177/11297298221103201
Isabella Santomauro, Daiana Campani, Valentina Tiozzo, Barbara Barletta, Lorenza Scotti, Michela Barisone, Alberto Dal Molin

Venous access devices are used in health care. To prevent occlusions the evidence confirmed the need for routine catheter flushing before and after infusion as well as at the end of use. To date, the efficacy of heparin has not been demonstrated. The aim of this study was to evaluate the effectiveness of the locking of central venous catheters with heparin versus normal saline in adults to prevent occlusion, catheter-related infections and thrombosis in adults. A literature search using Medline, Embase, Cochrane Library and Cinahl was performed to identify all meta-analyses addressing the effectiveness of heparin versus normal saline in locking central venous catheters in adults. Four reviewers independently selected publications assessed quality and extracted data. Parameter estimates regarding occlusion, catheter- related infections and thrombosis were pooled using an umbrella review. We identified 6356 references. Seven systematic reviews were included in the study. Most of the studies included in the systematic reviews were conducted in oncohaematology departments, intensive care and cardiac surgery units among patients with multiple diseases and chronicity. Most studies report a heparin concentration of 10 to 5000 IU/ml versus normal saline and other solutions. There was no evidence that heparin was more effective than normal saline in reducing complications such as occlusion, catheter-related infections and thrombosis. No statistically significant difference was found between heparin and normal saline in reducing catheter occlusion. Heparin is not superior compared to normal saline.

静脉通路装置用于医疗保健。为防止闭塞,有证据证实有必要在输液前后和使用结束时对导管进行常规冲洗。迄今为止,肝素的功效尚未得到证实。本研究旨在评估用肝素锁定成人中心静脉导管与用生理盐水锁定成人中心静脉导管对预防成人中心静脉导管闭塞、导管相关感染和血栓形成的效果。我们使用 Medline、Embase、Cochrane 图书馆和 Cinahl 进行了文献检索,以确定所有关于肝素与生理盐水对成人中心静脉导管锁定效果的荟萃分析。四位审稿人独立选择出版物,评估质量并提取数据。采用总括回顾法对有关闭塞、导管相关感染和血栓形成的参数估计进行了汇总。我们确定了 6356 篇参考文献。其中包括七篇系统综述。纳入系统综述的大多数研究都是在肿瘤科、重症监护室和心脏外科进行的,研究对象是患有多种疾病和慢性病的患者。大多数研究报告称,肝素浓度为 10 至 5000 IU/ml,而正常生理盐水和其他溶液的肝素浓度为 10 至 5000 IU/ml。没有证据表明肝素在减少闭塞、导管相关感染和血栓形成等并发症方面比生理盐水更有效。在减少导管闭塞方面,肝素与生理盐水之间没有明显的统计学差异。肝素与生理盐水相比并无优势。
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