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Contents Vol. 50, 2023 目录 第 50 卷,2023 年
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-12-01 DOI: 10.1159/000535411
MD – Peter Schlenke, PhD – Peter Bugert, MD Beate Mayer, MD Axel Pruß, MD Franz F. Wagner, MD Patrick Wuchter, PhD – Jason Acker, MD Gregor Bein, MD – Reinhard Burger, Robert Koch, PhD Toni Cathomen, PhD Jens Dreier, MD Hermann Eichler, MD – Andreas Humpe, MD Harald Klüter, MD – Jens Meier, MD – Rainer Moog, German Red, PhD – Bristol Andrew D. Mumford, CardioVascular, PhD – Thierry Peyrard, MD – Erwin Strasser, PhD – Pieter F. van der Meer, MD – Mark H. Yazer, E. Strasser, J. Piñeyroa, J. Cid, M. Lozano, P. Schlenke, von Heymann, Berlin Lier, H. Cologne, C. Rosenthal, L. Kaufner, Berlin, P.F.W. Strengers, Amsterdam, J. Cottrell, A. Al Sanani, I. Ogu, D. Chaffin, WV Huntington, D’Alessandro, P. A. Bugert, Research Articles, Meta-Analysis Qin, X. G. Han
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引用次数: 0
Congratulation, Appraisal, and Comment on the 25 Years Anniversary of Serious Hazards of Blood Transfusion 对《输血的严重危害》发表 25 周年的祝贺、评价和评论
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-11-27 DOI: 10.1159/000532049
Thomas Frietsch, Maria B. Rondinelli, Jerrold H. Levy
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引用次数: 0
In vitro Hemostatic Functions of Cold-Stored Platelets 冷藏血小板的体外止血功能
IF 2.2 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-11-16 DOI: 10.1159/000533735
J. Kirschall, G. Uzun, T. Bakchoul, I. Marini
Background: Transfusion of platelets is a life-saving medical strategy used worldwide to treat patients with thrombocytopenia as well as platelet function disorders. Summary: Until the end of 1960s, platelets were stored in the cold because of their superior hemostatic functionality. Cold storage of platelets was then abandoned due to better posttransfusion recovery and survival of room temperature (RT)-stored platelets, demonstrated by radioactive labeling studies. Based on these findings, RT became the standard condition to store platelets for clinical applications. Evidence shows that RT storage increases the risk of septic transfusion reactions associated with bacterial contamination. Therefore, the storage time is currently limited to 4–7 days, according to the national guidelines, causing a constant challenge to cover the clinical request. Despite the enormous efforts made to optimize storage conditions of platelets, the quality and efficacy of platelets still decrease during the short storage time at RT. In this context, during the last years, cold storage has seen a renaissance due to the better hemostatic functionality, reduced risk of bacterial contamination, and potentially longer storage time. Key Messages: In this review, we will focus on the impact of cold storage on the in vitro platelet functions as promising alternative storage temperature for future medical applications.
背景:输注血小板是全世界用于治疗血小板减少症和血小板功能障碍患者的一种挽救生命的医疗策略。摘要:直到 20 世纪 60 年代末,血小板一直被冷藏储存,因为其具有卓越的止血功能。后来,经放射性标记研究证明,室温(RT)储存的血小板输血后恢复和存活率更高,因此放弃了低温储存血小板。基于这些研究结果,室温成为临床应用中储存血小板的标准条件。有证据表明,室温储存会增加与细菌污染有关的脓毒性输血反应的风险。因此,根据国家指导方针,目前的储存时间仅限于 4-7 天,这给满足临床需求带来了持续挑战。尽管在优化血小板储存条件方面做出了巨大努力,但在 RT 短时间储存期间,血小板的质量和功效仍会下降。在这种情况下,冷藏血小板由于止血功能更好、细菌污染风险更低、储存时间更长等优点,在过去几年中得到了复兴。关键信息:在这篇综述中,我们将重点讨论冷藏对体外血小板功能的影响,冷藏温度是未来医疗应用中很有前景的替代储存温度。
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引用次数: 0
CRISPR/Cas9-Editing K562 Cell Line as a Potential Tool in Transfusion Applications: Knockout of Vel Antigen Gene CRISPR/ cas9编辑K562细胞系作为输血应用的潜在工具:敲除Vel抗原基因
4区 医学 Q3 HEMATOLOGY Pub Date : 2023-11-02 DOI: 10.1159/000534012
Jiaxuan Yang, Aijing Li, Minghao Li, Shulin Ruan, Luyi Ye
Introduction: The Vel– phenotype is a rare blood group, and it is challenging for identifying this phenotype due to limited available reagents. Moreover, there are relatively few studies on genomic editing of erythroid antigens and generation of knockout (KO) cell lines at present. Methods: To identify the high-efficiency small-guiding RNA (sgRNA) sequence, candidate sgRNAs were transfected into HEK 293T cells and analyzed using Sanger sequencing. Following this, the high-efficiency sgRNA was transfected into K562 cells using lentivirus transduction to generate KO Vel blood group gene cells. The expression of the Vel protein was detected using Western blot on single-cell clones. Additionally, flow cytometry was used to detect the erythroid markers CD235a and CD71. Hemoglobin quantification and Giemsa staining were also performed to evaluate the erythroid differentiation of KO clones induced by hemin. Results: The high-efficiency sgRNA was successfully obtained and used for CRISPR-Cas9 editing in K562 cells. After limiting dilution and screening, two KO clones had either deleted 2 or 4 bases and showed no expression of the Vel protein. In the hemin-induced KO clone, there was a significant difference in erythroid marker and hemoglobin quantification compared to untreated cells. The morphological changes were also observed for the hemin-induced KO clone. Conclusion: In this study, a highly efficient sgRNA was screened out and used to generate Vel erythroid antigen KO single-cell clones in K562 cells. The edited cells could then be induced to undergo erythroid differentiation with the use of hemin.
& lt; b> & lt; i>简介:& lt; / i> & lt; / b>Vel -表现型是一种罕见的血型,由于可用的试剂有限,鉴定这种表现型具有挑战性。此外,目前对红系抗原的基因组编辑和基因敲除(KO)细胞系的产生的研究相对较少。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>为了鉴定高效小导向RNA (high-efficiency small-guiding RNA, sgRNA)序列,我们将候选sgRNA转染到HEK 293T细胞中,并使用Sanger测序进行分析。随后,利用慢病毒转导将高效sgRNA转染到K562细胞中,生成KO Vel血型基因细胞。用Western blot检测单细胞克隆中Vel蛋白的表达。流式细胞术检测红细胞标记物CD235a和CD71。血红蛋白定量和Giemsa染色评价血红素诱导KO克隆的红系分化。& lt; b> & lt; i>结果:& lt; / i> & lt; / b>成功获得高效sgRNA,并将其用于K562细胞的CRISPR-Cas9编辑。经过有限稀释和筛选,两个KO克隆缺失了2个或4个碱基,没有表达Vel蛋白。在血红素诱导的KO克隆中,红细胞标记和血红蛋白定量与未处理的细胞相比有显著差异。血红素诱导的KO克隆在形态学上也发生了变化。& lt; b> & lt; i>结论:& lt; / i> & lt; / b>本研究筛选到高效的sgRNA,用于在K562细胞中生成Vel红细胞抗原KO单细胞克隆。然后利用血红素诱导编辑后的细胞进行红系分化。
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引用次数: 0
Patient Blood Management: We Still Have Work to Do 患者血液管理:我们仍有工作要做
4区 医学 Q3 HEMATOLOGY Pub Date : 2023-10-25 DOI: 10.1159/000534087
Patrick Meybohm, Lotta Hof, Suma Choorapoikayil, Kai Zacharowski
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引用次数: 0
Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing evorpacept诱导的干扰及其在输血前检测中的应用
4区 医学 Q3 HEMATOLOGY Pub Date : 2023-10-25 DOI: 10.1159/000534273
Eungjun Yoon, Tae Yeul Kim, Hyungsuk Kim, Duck Cho
Introduction: Evorpacept is a CD47-blocking agent currently being developed for the treatment of various cancers. Interference by evorpacept in pretransfusion compatibility testing has been reported at limited plasma concentrations. Although various mitigation strategies have been proposed, none are practical. This in vitro study assessed evorpacept-induced interference at extended concentrations and investigated the capability of a novel mitigation agent, Evo-NR. Methods: Antibody screening tests were performed on evorpacept-spiked plasma with (anti-E and anti-Jka) or without alloantibodies at evorpacept concentrations up to 2,000 μg/mL using manual gel cards and automated analyzers. Evorpacept-coated red blood cells (RBCs) (rr [ce/ce], Fy[a+b−], S−s+) were tested by direct antiglobulin testing (DAT) and antigen typing using anti-Fyb and anti-S reagents at indirect antiglobulin testing (IAT) phase. Evo-NR was used to resolve the interference in plasma and RBC samples. Flow cytometry was used to assess the mitigation effects. Results: Evorpacept-spiked plasma showed panreactive interference in antibody screening tests using manual gel cards (2+ to 3+) and automated analyzers (4+). A carryover effect was also observed in the automated analyzers. The use of a 3- to 6-fold molar excess of Evo-NR effectively resolved the interference in the plasma and enabled accurate alloantibody identification. Although the reduction in evorpacept binding to RBCs was identified via flow cytometry, Evo-NR was incapable of resolving the serologic interference observed in DAT and antigen typing at IAT phase. Discussion: Evorpacept showed constant panreactivity and a carryover effect at high concentrations. Evo-NR successfully resolved the interference in the plasma samples and could be considered a practical and efficient mitigation solution. Implementation of Evo-NR has the potential to support RBC transfusion for patients undergoing evorpacept treatment.
& lt; b> & lt; i>简介:& lt; / i> & lt; / b>Evorpacept是一种cd47阻断剂,目前正在开发用于治疗各种癌症。据报道,在有限的血浆浓度下,evorpacept对输血前相容性试验的干扰。虽然提出了各种缓解战略,但没有一种是实际可行的。这项体外研究评估了evorpacept在大浓度下诱导的干扰,并研究了一种新型缓解剂Evo-NR的能力。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>在evorpacept浓度高达2000 μg/mL时,使用手动凝胶卡和自动分析仪对加入evorpacept的血浆进行抗体筛选试验(抗e和抗jk <sup>a</sup>)或不含同种异体抗体。用直接抗球蛋白试验(DAT)检测evorpacept包被红细胞(rr [ce/ce], Fy[a+b−],S−S +),并用anti-Fy<sup>间接抗球蛋白试验(IAT)阶段的抗s试剂。Evo-NR用于消除血浆和红细胞样品中的干扰。采用流式细胞术评价缓解效果。& lt; b> & lt; i>结果:& lt; / i> & lt; / b>evorpacept加标血浆在使用手工凝胶卡(2+至3+)和自动分析仪(4+)进行抗体筛选试验时显示出泛反应性干扰。在自动分析仪中也观察到结转效应。使用3- 6倍摩尔过量的Evo-NR有效地解决了血浆中的干扰,并实现了准确的同种异体抗体鉴定。虽然通过流式细胞术鉴定了evorpacept与红细胞结合的减少,但Evo-NR无法解决IAT期DAT和抗原分型中观察到的血清学干扰。& lt; b> & lt; i>讨论:& lt; / i> & lt; / b>Evorpacept在高浓度下表现出持续的全反应性和携带效应。Evo-NR成功地解决了等离子体样品中的干扰,可以被认为是一种实用而有效的缓解方案。Evo-NR的实施有可能支持接受evorpacept治疗的患者输血。
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引用次数: 0
Indocyanine Green-Labeled Platelets for Survival and Recovery Studies 吲哚菁绿色标记血小板用于生存和恢复研究
4区 医学 Q3 HEMATOLOGY Pub Date : 2023-10-16 DOI: 10.1159/000533623
Johannes-Moritz von Behren, Jan Wesche, Andreas Greinacher, Konstanze Aurich
Introduction: Before being implemented in daily clinical routine, new production strategies for platelet concentrates (PCs) must be validated for their efficacy. Besides in vitro testing, the establishment of new methods requires the labeling of platelets for in vivo studies of platelets’ survival and recovery. Indocyanine green (ICG) is a Food and Drug Administration-approved near-infrared (NIR) fluorescent dye for diagnostic use in vivo, suitable for non-radioactive direct cell labeling of platelets. Methods: Platelets from PCs in storage solutions with different plasma concentrations were labeled with ICG up to concentrations of 200 μm. Whole blood (WB) was used as an ex vivo matrix to monitor the labeling stability of ICG-labeled platelets. The impact of labeling processes was assessed by the quantification of CD62P expression and PAC-1 binding as platelet function markers. Platelet aggregation was analyzed by light transmission aggregometry. ICG-labeling efficiency and stability of platelets were determined by flow cytometry. Results: Platelets from PCs could be successfully labeled with 10 μm ICG after 1 and 4 days of storage. The best labeling efficiency of 99.8% ± 0.1% (immediately after labeling) and 81% ± 6.2% (after 24 h incubation with WB) was achieved by plasma replacement by 100% platelet additive solution for the labeling process. Since the washing process slightly impaired platelet function, ICG labeling itself did not affect platelets. Immediately after the ICG-labeling process, plasma was re-added, resulting in a recovered platelet function. Conclusion: We developed a Good Manufacturing Practice compatible protocol for ICG fluorescent platelet labeling suitable for survival and recovery studies in vivo as a non-radioactive labeling alternative.
& lt; b> & lt; i>简介:& lt; / i> & lt; / b>在应用于日常临床常规之前,血小板浓缩物(PCs)的新生产策略必须对其有效性进行验证。除了体外测试外,新方法的建立还需要对血小板进行标记,以便在体内研究血小板的存活和恢复。吲哚菁绿(ICG)是美国食品和药物管理局批准用于体内诊断的近红外(NIR)荧光染料,适用于血小板的非放射性直接细胞标记。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>在不同血浆浓度的储存溶液中,用ICG标记血浆血小板,浓度为200 μ<sc>m</sc>全血(WB)作为离体基质监测icg标记血小板的标记稳定性。通过定量CD62P表达和PAC-1结合作为血小板功能标志物来评估标记过程的影响。光透射聚集法分析血小板聚集。流式细胞术检测血小板的icg标记效率和稳定性。& lt; b> & lt; i>结果:& lt; / i> & lt; / b>用10 μ<sc>m</sc>1天和4天后的ICG。用100%血小板添加液替代血浆进行标记时,标记效率为99.8%±0.1%(标记后立即)和81%±6.2% (WB孵育24 h后)。由于洗涤过程轻微损害血小板功能,因此ICG标记本身并不影响血小板。在icg标记过程后,立即重新添加血浆,导致血小板功能恢复。& lt; b> & lt; i>结论:& lt; / i> & lt; / b>我们为ICG荧光血小板标记开发了一种与良好生产规范兼容的方案,适用于活体生存和恢复研究,作为一种非放射性标记替代方案。
{"title":"Indocyanine Green-Labeled Platelets for Survival and Recovery Studies","authors":"Johannes-Moritz von Behren, Jan Wesche, Andreas Greinacher, Konstanze Aurich","doi":"10.1159/000533623","DOIUrl":"https://doi.org/10.1159/000533623","url":null,"abstract":"<b><i>Introduction:</i></b> Before being implemented in daily clinical routine, new production strategies for platelet concentrates (PCs) must be validated for their efficacy. Besides in vitro testing, the establishment of new methods requires the labeling of platelets for in vivo studies of platelets’ survival and recovery. Indocyanine green (ICG) is a Food and Drug Administration-approved near-infrared (NIR) fluorescent dye for diagnostic use in vivo, suitable for non-radioactive direct cell labeling of platelets. <b><i>Methods:</i></b> Platelets from PCs in storage solutions with different plasma concentrations were labeled with ICG up to concentrations of 200 μ<sc>m</sc>. Whole blood (WB) was used as an ex vivo matrix to monitor the labeling stability of ICG-labeled platelets. The impact of labeling processes was assessed by the quantification of CD62P expression and PAC-1 binding as platelet function markers. Platelet aggregation was analyzed by light transmission aggregometry. ICG-labeling efficiency and stability of platelets were determined by flow cytometry. <b><i>Results:</i></b> Platelets from PCs could be successfully labeled with 10 μ<sc>m</sc> ICG after 1 and 4 days of storage. The best labeling efficiency of 99.8% ± 0.1% (immediately after labeling) and 81% ± 6.2% (after 24 h incubation with WB) was achieved by plasma replacement by 100% platelet additive solution for the labeling process. Since the washing process slightly impaired platelet function, ICG labeling itself did not affect platelets. Immediately after the ICG-labeling process, plasma was re-added, resulting in a recovered platelet function. <b><i>Conclusion:</i></b> We developed a Good Manufacturing Practice compatible protocol for ICG fluorescent platelet labeling suitable for survival and recovery studies in vivo as a non-radioactive labeling alternative.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"225 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136078834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A German-Wide Systematic Study on Mobilization and Collection of Hematopoietic Stem Cells in Poor Mobilizer Patients with Multiple Myeloma prior to Autologous Stem Cell Transplantation 在德国范围内对动员能力差的多发性骨髓瘤患者在自体干细胞移植前造血干细胞的动员和收集进行系统研究
4区 医学 Q3 HEMATOLOGY Pub Date : 2023-10-16 DOI: 10.1159/000531935
Max Bittrich, Katharina Kriegsmann, Carola Tietze-Stolley, Kamram Movassaghi, Matthias Grube, Vladan Vucinic, Daniela Wehler, Andreas Burchert, Martin Schmidt-Hieber, Andreas Rank, Heinz A. Dürk, Bernd Metzner, Christoph Kimmich, Marcus Hentrich, Christian Kunz, Frank Hartmann, Cyrus Khandanpour, Maike de Wit, Udo Holtick, Michael Kiehl, Andrea Stoltefuß, Alexander Kiani, Ralph Naumann, Christian W. Scholz, Hans-Joachim Tischler, Martin Görner, Franziska Brand, Martin Ehmer, Nicolaus Kröger
Introduction: In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34+ precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g., &gt;10/µL) CD34+ cell counts into the peripheral blood and are considered as poor mobilizers (PM). Because failure to achieve sufficient CD34+ cell mobilization can negatively affect important clinical treatment endpoints, the use of plerixafor (PLX) was approved to increase CD34+ mobilization in PM patients. Methods: The German non-interventional, multicenter, open-label, prospective OPTIMOB study evaluated HSC mobilization strategies prior to planned ASCT in adult patients with hematologic malignancies (lymphomas or multiple myeloma [MM]) focusing on PM patients. PM patients were defined as follows: (1) never achieving ≥20 CD34+ cells/µL before 1st apheresis, (2) receiving PLX at any timepoint of mobilization, (3) their initially planned stem cell yield had to be reduced, or (4) they had not received apheresis due to low CD34+ count in peripheral blood. Results: 168 of 475 MM patients (35%) participating in the OPTIMOB study were classified as PM, and 155 of them (92%) received PLX (PM+PLX) during the study. PM patients were 40–78 years old, slightly more often male (n = 97, 58%), mostly newly diagnosed (n = 146, 87%) and received highly individualized previous treatments. Ninety-four of the PMs underwent chemotherapy mobilization (65%), and 51 patients (35%) received steady-state mobilization with G-CSF only during 1st mobilization attempt. 92% of the total PM population (n = 155) underwent apheresis, 78% of them (n = 117) achieved &gt;2.0 × 106 CD34+ cells/kg body weight on the 1st day of apheresis. PM+PLX had a higher median total collection result than those PM patients without PLX support (7.2 vs. 5.7 × 106 CD34+ cells/kg body weight). In total, ASCT was performed in 136 PM+PLX (88%) versus 8 PM−PLX patients (62%). Conclusion: The OPTIMOB study showed that a considerable proportion of adult MM patients in Germany are PMs. Even though most of PMs were supported with PLX in the OPTIMOB study, PM-PLX also successfully mobilized HSCs, allowing ASCT in majority of all PMs. However, further analyses are required for treatment optimization in PMs.
& lt; b> & lt; i>简介:& lt; / i> & lt; / b>在有临床指征的自体造血干细胞移植(ASCT)患者中,充分动员CD34<sup>+<前体细胞进入外周血对于确保在强化治疗前收集足够的造血干细胞(HSC)至关重要。然而,在标准的基于粒细胞集落刺激因子(G-CSF)的动员方案中,有重要的少数患者无法动员足够的CD34<sup>+</sup>细胞计数进入外周血,被认为是不良动员(PM)。因为不能获得足够的CD34<sup>+</sup>细胞动员会对重要的临床治疗终点产生负面影响,使用plerixafor (PLX)被批准增加CD34<sup>PM患者的活动。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>德国的一项非介入性、多中心、开放标签、前瞻性OPTIMOB研究评估了成人血液恶性肿瘤(淋巴瘤或多发性骨髓瘤[MM])患者在计划ASCT前的HSC动员策略,重点是PM患者。PM患者定义如下:(1)从未达到≥20 CD34<sup>+</sup>(2)在动员的任何时间点接受PLX,(3)他们最初计划的干细胞产量必须减少,或(4)由于低CD34< +</sup>外周血计数。& lt; b> & lt; i>结果:& lt; / i> & lt; / b>参与OPTIMOB研究的475例MM患者中有168例(35%)被分类为PM,其中155例(92%)在研究期间接受了PLX (PM+PLX)治疗。PM患者年龄在40-78岁之间,男性稍多(<i>n</i>= 97,58%),大多数是新诊断(<i>n</i>= 146,87%),并接受高度个性化的既往治疗。94名pm接受化疗动员(65%),51名患者(35%)仅在第一次动员尝试时接受G-CSF的稳态动员。占PM总人口的92% (<i>n</i>= 155例,其中78% (<i>n</i>= 117)达到>2.0 × 10<sup>6</sup>CD34< sup> + & lt; / sup>采血第1天细胞数/kg体重。PM+PLX的中位总收集结果高于不支持PLX的PM患者(7.2 vs. 5.7 × 10<sup>6</sup>CD34< sup> + & lt; / sup>细胞/公斤体重)。总的来说,136例PM+PLX患者(88%)和8例PM - PLX患者(62%)进行了ASCT检查。& lt; b> & lt; i>结论:& lt; / i> & lt; / b>OPTIMOB研究显示,德国成年MM患者中有相当大比例为pm。尽管在OPTIMOB研究中,大多数pmms都得到了PLX的支持,但PM-PLX也成功地动员了hsc,允许大多数pmms进行ASCT。然而,需要进一步的分析来优化pm中的处理。
{"title":"A German-Wide Systematic Study on Mobilization and Collection of Hematopoietic Stem Cells in Poor Mobilizer Patients with Multiple Myeloma prior to Autologous Stem Cell Transplantation","authors":"Max Bittrich, Katharina Kriegsmann, Carola Tietze-Stolley, Kamram Movassaghi, Matthias Grube, Vladan Vucinic, Daniela Wehler, Andreas Burchert, Martin Schmidt-Hieber, Andreas Rank, Heinz A. Dürk, Bernd Metzner, Christoph Kimmich, Marcus Hentrich, Christian Kunz, Frank Hartmann, Cyrus Khandanpour, Maike de Wit, Udo Holtick, Michael Kiehl, Andrea Stoltefuß, Alexander Kiani, Ralph Naumann, Christian W. Scholz, Hans-Joachim Tischler, Martin Görner, Franziska Brand, Martin Ehmer, Nicolaus Kröger","doi":"10.1159/000531935","DOIUrl":"https://doi.org/10.1159/000531935","url":null,"abstract":"<b><i>Introduction:</i></b> In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34<sup>+</sup> precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g., &amp;gt;10/µL) CD34<sup>+</sup> cell counts into the peripheral blood and are considered as poor mobilizers (PM). Because failure to achieve sufficient CD34<sup>+</sup> cell mobilization can negatively affect important clinical treatment endpoints, the use of plerixafor (PLX) was approved to increase CD34<sup>+</sup> mobilization in PM patients. <b><i>Methods:</i></b> The German non-interventional, multicenter, open-label, prospective OPTIMOB study evaluated HSC mobilization strategies prior to planned ASCT in adult patients with hematologic malignancies (lymphomas or multiple myeloma [MM]) focusing on PM patients. PM patients were defined as follows: (1) never achieving ≥20 CD34<sup>+</sup> cells/µL before 1st apheresis, (2) receiving PLX at any timepoint of mobilization, (3) their initially planned stem cell yield had to be reduced, or (4) they had not received apheresis due to low CD34<sup>+</sup> count in peripheral blood. <b><i>Results:</i></b> 168 of 475 MM patients (35%) participating in the OPTIMOB study were classified as PM, and 155 of them (92%) received PLX (PM+PLX) during the study. PM patients were 40–78 years old, slightly more often male (<i>n</i> = 97, 58%), mostly newly diagnosed (<i>n</i> = 146, 87%) and received highly individualized previous treatments. Ninety-four of the PMs underwent chemotherapy mobilization (65%), and 51 patients (35%) received steady-state mobilization with G-CSF only during 1st mobilization attempt. 92% of the total PM population (<i>n</i> = 155) underwent apheresis, 78% of them (<i>n</i> = 117) achieved &amp;gt;2.0 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg body weight on the 1st day of apheresis. PM+PLX had a higher median total collection result than those PM patients without PLX support (7.2 vs. 5.7 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg body weight). In total, ASCT was performed in 136 PM+PLX (88%) versus 8 PM−PLX patients (62%). <b><i>Conclusion:</i></b> The OPTIMOB study showed that a considerable proportion of adult MM patients in Germany are PMs. Even though most of PMs were supported with PLX in the OPTIMOB study, PM-PLX also successfully mobilized HSCs, allowing ASCT in majority of all PMs. However, further analyses are required for treatment optimization in PMs.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136079073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Challenges for Plasma-Derived Medicinal Products 血浆衍生药品面临的挑战
4区 医学 Q3 HEMATOLOGY Pub Date : 2023-10-11 DOI: 10.1159/000533736
Rainer Moog, Teija Dehmer-Laitinen, Uwe Taborski
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引用次数: 0
Ozone Improves Oxygenation and Offers Organ Protection after Autologous Blood Transfusion in a Simulated Carbon Dioxide Pneumoperitoneal Environment in a Rabbit Hemorrhagic Shock Model 在模拟二氧化碳气腹环境的兔失血性休克模型中,臭氧改善自体输血后的氧合并提供器官保护
4区 医学 Q3 HEMATOLOGY Pub Date : 2023-09-27 DOI: 10.1159/000527934
Yu Gan, Xue Tian, Han Yao, Fei Huo, Yi Feng
Objectives: Autologous blood transfusion techniques are well applied in surgery, but the red blood cells (RBCs) collected during laparoscopic surgery may forfeit their ability to oxygenate. O3 is a potent oxidation gas. This study investigates whether O3 could improve the oxygen-carrying capacity of RBCs, reduce inflammatory reactions, and offer organ protection. Methods: We established a hemorrhagic shock model in rabbits, and simulated CO2 pneumoperitoneum and O3 were applied before autologous blood transfusion. Perioperative mean arterial pressure and arterial blood gas were recorded, blood gas and RBC morphology of collected blood were analyzed, plasma IL-6, ALT, AST, CRE, and lung histopathology POD0 and POD3 were tested, as well as postoperative survival quality. Results: Autologous blood that underwent simulated CO2 pneumoperitoneum had a lower pH and SaO2 and a higher PaCO2 than the control group. After O3 treatment, PaO2 and SaO2 increased significantly, with unchanged pH values and PaCO2. RBCs in autologous blood were drastically deformed after CO2 conditioning and then reversed to normal by O3 treatment. Rabbits that received CO2-conditioned autologous blood had a compromised survival quality after surgery, higher plasma IL-6 levels, higher lung injury scores on POD0, higher ALT and AST levels on POD3, and O3 treatment alleviated these adverse outcomes. Conclusion: O3 can restore RBC function, significantly improve blood oxygenation under simulated CO2 pneumoperitoneum, offer organ protection, and improve the postoperative survival quality in the rabbit hemorrhage shock model.
& lt; b> & lt; i>目标:& lt; / i> & lt; / b>自体输血技术在外科手术中得到了很好的应用,但在腹腔镜手术中收集的红细胞(rbc)可能会丧失其氧合能力。O< sub> 3 & lt; / sub>是一种强氧化气体。本研究探讨O<sub>3</sub>可以提高红细胞的携氧能力,减少炎症反应,并提供器官保护。& lt; b> & lt; i>方法:& lt; / i> & lt; / b>我们建立家兔失血性休克模型,模拟CO<sub>2<气腹和O<sub>3</sub>应用于自体输血前。记录围手术期平均动脉压、动脉血气,分析采血血气及红细胞形态,检测血浆IL-6、ALT、AST、CRE及肺组织病理学POD0、POD3,以及术后生存质量。& lt; b> & lt; i>结果:& lt; / i> & lt; / b>接受模拟CO<sub>2</sub>气腹pH值较低,SaO<sub>2</sub>和更高的PaCO<sub>2</sub>比对照组多。后O< sub> 3 & lt; / sub>治疗,PaO< sub> 2 & lt; / sub>和SaO< sub> 2 & lt; / sub>显著增加,pH值和PaCO<sub>2</sub>不变。CO<sub>2</sub>条件反射,然后通过O<sub>3</sub>治疗。接受CO<sub>2</sub>供血的家兔术后生存质量下降,血浆IL-6水平升高,POD0肺损伤评分升高,POD3 ALT和AST水平升高,O<sub>3</sub>治疗减轻了这些不良后果。& lt; b> & lt; i>结论:& lt; / i> & lt; / b>O< sub> 3 & lt; / sub>可以恢复红细胞功能,显著改善模拟CO<sub>2</sub>气腹,提供器官保护,提高兔失血性休克模型术后生存质量。
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引用次数: 0
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Transfusion Medicine and Hemotherapy
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