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Development of molecular sterility assay for rapid quality release of cord blood erythrocytes units for transfusion. 开发分子无菌测定法,用于快速发布输血用脐带血红细胞单位的质量。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-08 DOI: 10.1111/trf.18084
Laia Closa, Dinara Samarkanova, Carina Lera, Noemí Gonzalez, Mireia Lloret, Margarita Codinach, Gemma Aran, Jesús Fernandez-Sojo, Francisco Vidal, Maria Gloria Soria, Sergi Querol

Background: Umbilical cord blood (CB) units stored in banks are an important source of hematopoietic stem cells for transplantation and other cell therapies. New applications, such as their use in transfusions, require rapid quality release as cord blood red blood cells (CB-RBC) have a shorter shelf life.

Study design and methods: This project aims to investigate the most prevalent microbial contaminants in CB preparations and validate a rapid sterility testing strategy for CB-RBC based on an automated system (BACT/ALERT®) in tandem with a molecular assay (real-time PCR) capable of detecting at least 100 CFU/mL of Cutibacterium acnes in CB-RBC to accelerate the detection of the most common slow-growing bacteria.

Results: Microbial contamination incidence was assessed by reviewing 4696 CB sterility tests, revealing a positivity rate of 3.4%, with C. acnes being the most common slow-growing pathogen. The BACT/ALERT® system, which was validated according to European Pharmacopeia guidelines, was an appropriate method for sterility testing of CB-RBC, although it required up to 14 days of culture to detect C. acnes when iFAPlus and iFNPlus bottles were used to neutralize antimicrobials. Interestingly, the BACT/ALERT® method detected C. acnes at 30 CFU/mL within 14 days, while real-time PCR identified concentrations ≥65 CFU/mL by Day 4.

Discussion: In conclusion, we developed a rapid sterility testing strategy that combines automated culture systems and real-time PCR for early microbial contamination, enhancing CB-RBC shelf life for transfusion and emphasizing the importance of combining detection methods.

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引用次数: 0
"Are my blood products coming?": Implementation of a novel blood product tracker in the electronic health record system.
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-08 DOI: 10.1111/trf.18089
Tina Chai, Connor Hartzell, Randy Winstead, Kirk Krokosky, Kaycie Atchison, Angela Mueller, Erika Hall, Jonathan P Wanderer, Jennifer Andrews

Background: Blood transfusions are the most common procedure performed in American hospitals. The steps required for blood product delivery are often misunderstood by providers, leading to numerous phone calls to the blood bank requesting order status. Distracting calls can lengthen turnaround time, especially during blood product or staff shortages. We sought a tool to address these questions and reduce distraction. This study highlights a novel blood tracker tool implemented in the electronic health record (EHR) that allows providers to see their blood order's status.

Study design and methods: With a multidisciplinary team of healthcare professionals, we constructed a user-friendly blood tracker highly visible in our EHR. It shows the status of a blood product in real time from "order printed" to "preparing" to "on its way." We surveyed blood bank technologists to determine if call volume and distraction changed.

Results: We counted the number of views per month as a surrogate of usage. The blood tracker was viewed 109,626 times per month on average from January through December 2023. The fraction of technologists who received 21 or more calls per shift decreased by 47%.

Discussion: We successfully constructed and implemented a novel blood tracker into our EHR that relays the status of a blood product. It is a highly viewed piece of information in our EHR and decreases blood bank call volume as reported by blood bank technologists. Its success demonstrates that closed-loop communication between the lab and providers regarding blood products is beneficial within our organization and potentially others.

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引用次数: 0
Impact of input volume on red cell quality in deglycerolized RBCs using a modified ACP-215 protocol.
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-08 DOI: 10.1111/trf.18088
Anita Howell, Angela Hill, Wanda Lefresne, Brandie Dennis, Tracey R Turner, Qi-Long Yi, Carly Olafson, Nishaka William, Jason P Acker

Background: The ACP 215 automated cell processor is used to glycerolize and deglycerolize red cell concentrates (RCCs). Its primary advantage over the COBE 2991, previously used to cryopreserve RCCs, is that it maintains a closed system enabling extended post-thaw expiry. However, it was observed that post-deglycerolization hematocrits (Hct) of units processed with the LN236 kit are markedly lower than those processed using the COBE 2991. Therefore, we intended to determine whether a modified process using a smaller volume deglycerolization kit (LN235) could increase the final Hct with limited deleterious effects on product characteristics.

Study design and methods: Two proof-of-concept (POC) studies, conducted to determine the feasibility of using the LN235 processing kit for deglycerolization, identified the necessary modifications to the pre- and post-deglycerolization process, after which a two-part study characterized the modified protocol. The impact of pre-cryopreservation storage duration (7-21 days), input red cell mass, and the type of CPD/SAGM RCC production method (red cell filtration and whole blood filtration) were investigated.

Results: Using the LN235 kit in conjunction with a volume reduction step for RCCs with a red cell mass exceeding 180 mL allowed for an ~8% increase in Hct. As expected, slightly lower recoveries were seen for large RCCs due to volume reduction; however, there were no other detrimental outcomes on product quality.

Conclusions: Leveraging the LN235 kit, recommended by Haemonetics for units with a red cell mass of ≤180 mL, can be used to increase the post-deglycerolization Hct of RCCs that exceed this volume.

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引用次数: 0
Comparison of two inline photopheresis systems: A paired crossover trial.
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-08 DOI: 10.1111/trf.18090
Nicola Piccirillo, Rossana Putzulu, Federica Fatone, Giuseppina Massini, Sabrina Giammarco, Elisabetta Metafuni, Maria Assunta Limongiello, Patrizia Chiusolo, Simona Sica, Luciana Teofili

Background: Extracorporeal photopheresis (ECP) has been demonstrated as an effective treatment for graft-versus-host disease (GvHD). The inline system was developed by Therakos in 1987. Recently, Fresenius Kabi implemented an integration of cell separator Amicus and a UVA photoactivation device (Phelix), realizing an inline photopheresis system.

Study design and methods: In 2022 we designed a prospective paired crossover trial (NCT05718674) comparing two integrated ECP protocols: Therakos CELLEX and Amicus ECP system. Twenty patients affected by corticosteroid resistant GvHD were submitted to 80 ECP, 40 paired procedures.

Results: All procedures were well tolerated, with no significant differences in procedure duration. CELLEX cell product showed higher granulocytes and platelet content, while Amicus cell product exhibited higher enrichment of lymphocytes, resulting in significantly higher MNC purity (92.9% vs. 84%). A significantly higher granulocytes and platelets absolute content was observed in CELLEX cell products, while Amicus cell products showed a significantly higher number of TNCs and MNCs. Differences in granulocyte and platelet content remained significant even after normalization of the data according to blood volume processed. These findings are confirmed by a statistically significant higher CE2% for CELLEX for granulocytes and platelets along with the lack of significant difference observed for TNCs and MNCs.

Discussion: Our analysis shows differences in the characteristics of the procedure and the cell product. Anyway, both devices are effective for performing ECP procedure, as they collect a cell product suitable for photopheresis. At present, our results represent the first data set comparing two available inline ECP devices.

{"title":"Comparison of two inline photopheresis systems: A paired crossover trial.","authors":"Nicola Piccirillo, Rossana Putzulu, Federica Fatone, Giuseppina Massini, Sabrina Giammarco, Elisabetta Metafuni, Maria Assunta Limongiello, Patrizia Chiusolo, Simona Sica, Luciana Teofili","doi":"10.1111/trf.18090","DOIUrl":"https://doi.org/10.1111/trf.18090","url":null,"abstract":"<p><strong>Background: </strong>Extracorporeal photopheresis (ECP) has been demonstrated as an effective treatment for graft-versus-host disease (GvHD). The inline system was developed by Therakos in 1987. Recently, Fresenius Kabi implemented an integration of cell separator Amicus and a UVA photoactivation device (Phelix), realizing an inline photopheresis system.</p><p><strong>Study design and methods: </strong>In 2022 we designed a prospective paired crossover trial (NCT05718674) comparing two integrated ECP protocols: Therakos CELLEX and Amicus ECP system. Twenty patients affected by corticosteroid resistant GvHD were submitted to 80 ECP, 40 paired procedures.</p><p><strong>Results: </strong>All procedures were well tolerated, with no significant differences in procedure duration. CELLEX cell product showed higher granulocytes and platelet content, while Amicus cell product exhibited higher enrichment of lymphocytes, resulting in significantly higher MNC purity (92.9% vs. 84%). A significantly higher granulocytes and platelets absolute content was observed in CELLEX cell products, while Amicus cell products showed a significantly higher number of TNCs and MNCs. Differences in granulocyte and platelet content remained significant even after normalization of the data according to blood volume processed. These findings are confirmed by a statistically significant higher CE2% for CELLEX for granulocytes and platelets along with the lack of significant difference observed for TNCs and MNCs.</p><p><strong>Discussion: </strong>Our analysis shows differences in the characteristics of the procedure and the cell product. Anyway, both devices are effective for performing ECP procedure, as they collect a cell product suitable for photopheresis. At present, our results represent the first data set comparing two available inline ECP devices.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Effect of the added plasma rinseback on residual cell types in plateletpheresis leukoreduction systems.
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-05 DOI: 10.1111/trf.18086
Kathleen Kelly, Jeff Finlon, Stefan Fulciniti, Deborah Lee, Micaela Jones, Susanne Marschner

Background: Platelets collected by the Trima Accel apheresis device (Terumo BCT) are automatically leukoreduced through a leukoreduction system (LRS) where WBCs are trapped in a conical-shaped LRS chamber. The content has been used as a valuable source of mononuclear cells for research purposes. In frequent, long-term platelet apheresis donors, lymphopenia has been associated with the use of LRS chambers, and implementation of plasma rinseback at the end of the procedure has been shown to mitigate the depletion of lymphocytes. In this report, the cellular content of the LRS chamber and remaining disposable was characterized with and without plasma rinseback.

Study design and methods: Trima disposable sets were obtained from apheresis platelet collections in 100% plasma or 35% plasma/65% PAS with or without plasma rinseback at the end of the collections. Cellular content was drained from the LRS chamber and the disposable and was characterized using a hematology analyzer and flow cytometer to establish total cell counts and proportions of RBC, platelet, and WBC subpopulations.

Results: LRS chambers contained approximately 109 WBCs, with the majority being lymphocytes and monocytes. The addition of plasma rinseback significantly decreased the number of WBCs remaining in the disposable, thereby increasing the number of WBCs returned to the donor. However, rinseback did not impact the WBC content of the LRS chamber itself.

Conclusions: Blood Centers using the Trima Accel instrument may reduce lymphopenia in regular platelet donors by implementing plasma rinseback, while ensuring the cellular content of the LRS chamber intended for research purposes remains unaffected.

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引用次数: 0
Planning antepartum directed donations in preparation for neonatal cardiac surgery in the absence of compatible donors.
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-02 DOI: 10.1111/trf.18087
Marc Bienz, Jessica Constanzo-Yanez, Nadia Baillargeon, Gabriel André Leiva-Torres, Mélissa Boileau, Marc Cloutier, Audrey Laforce-Lavoie, Nancy Robitaille

Background: Homozygous inheritance of the RN haplotype, characterized by the absence of the high frequency antigen Sec, as well as partial C and e antigens, is rare and is associated with potential for alloimmunization. Anti-Sec has been reported to be associated with a risk of delayed hemolytic transfusion reaction and hemolytic disease of the fetus and newborn (HDFN).

Results: We report the case of a 36-year-old pregnant woman with known sickle cell trait (SCT) and homozygous for the RN haplotype with anti-Sec, anti-c, and anti-e. Morphological ultrasound identified dextro-transposition of the great arteries in the fetus. Neonatal cardiac surgery was planned with cardiopulmonary bypass support. Due to the rarity of this genotype, there were no compatible donors in our registry. For this reason, in addition to two previously glycerolized maternal donations, the mother donated three units during pregnancy and one unit postpartum.

Discussion: This case highlights the many complexities for the blood supplier pertaining to organizing blood donations during pregnancy, the risk of leukoreduction failure and jellification during the deglycerolization process of units from donors with rare blood carrying the SCT, as well as planning the rare-blood inventory and managing expiry dates to provide transfusion support during delivery, neonatal surgery, and the postoperative period. This case also exemplifies the importance of a strong partnership between blood suppliers and medical teams.

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引用次数: 0
Serological and molecular characterization of novel ABO variants including an interesting B(A) subgroup. 新型 ABO 变体的血清学和分子特征,包括一个有趣的 B(A)亚群。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-07 DOI: 10.1111/trf.18039
Yunlei He, Lu Yu, Jiwei Zhang, Yiwen He, Di Niu, Gang Deng

Background: ABO grouping is the most important pretransfusion testing that is directly related to the safety of blood transfusion. A weak ABO subgroup is one of the important causes of an ABO grouping discrepancy. Here, we investigated the characterization of four novel ABO variants including a novel B(A) subgroup.

Study design and methods: RBCs were phenotyped by standard serology methods. The full coding regions of the ABO gene and the erythroid cell-specific regulatory elements in intron one were sequenced. The effect of the possible splice site variant was predicted by Alamut software. The 3D structural modeling of three relative B(A) enzymes (p.Met214Thr, p.Met214Val, and p.Met214Leu) were performed by PyMOL software.

Results: Four novel ABO alleles were identified with weak ABO expression in this study, in which two would lead to premature terminations, and two resulted in amino acid changes. In silico analysis revealed that the splice site variant c.155G>T had the potential to alter splice transcripts. 3D structural view shown that the variant amino acid position 214 was spatially adjacent to the donor recognition pocket residues (266Met and 268Ala) and just next to the 211DVD213 motif. The size of the side chain of Thr and Val is the smallest, Leu is medium, and Met is the largest, and the size changes in the critical position 214 may affect the donor recognition pocket.

Conclusion: Four ABO subgroup alleles were newly linked to different kinds of ABO variants and the possible mechanism through which they produce weak ABO subgroups was analyzed in silico.

背景:ABO 血型是输血前最重要的检测项目,直接关系到输血的安全性。ABO亚群薄弱是导致ABO血型不一致的重要原因之一。在此,我们研究了四种新型 ABO 变异的特征,其中包括一种新型 B(A)亚群:研究设计与方法:采用标准血清学方法对红细胞进行表型分析。对 ABO 基因的全部编码区和内含子一的红细胞特异性调控元件进行了测序。Alamut 软件预测了可能的剪接位点变异的影响。用 PyMOL 软件对三种相对 B(A)酶(p.Met214Thr、p.Met214Val 和 p.Met214Leu)进行了三维结构建模:结果:本研究发现了四种新型 ABO 等位基因,它们的 ABO 表达较弱,其中两种等位基因会导致过早终止,两种等位基因会导致氨基酸变化。硅学分析表明,剪接位点变异 c.155G>T 有可能改变剪接转录本。三维结构视图显示,变异氨基酸位置 214 在空间上与供体识别袋残基(266Met 和 268Ala)相邻,并且紧挨着 211DVD213 主题。Thr和Val的侧链大小最小,Leu中等,Met最大,关键位置214的大小变化可能会影响供体识别袋:结论:四种 ABO 亚群等位基因与不同类型的 ABO 变异有新的联系,并对它们产生弱 ABO 亚群的可能机制进行了硅学分析。
{"title":"Serological and molecular characterization of novel ABO variants including an interesting B(A) subgroup.","authors":"Yunlei He, Lu Yu, Jiwei Zhang, Yiwen He, Di Niu, Gang Deng","doi":"10.1111/trf.18039","DOIUrl":"10.1111/trf.18039","url":null,"abstract":"<p><strong>Background: </strong>ABO grouping is the most important pretransfusion testing that is directly related to the safety of blood transfusion. A weak ABO subgroup is one of the important causes of an ABO grouping discrepancy. Here, we investigated the characterization of four novel ABO variants including a novel B(A) subgroup.</p><p><strong>Study design and methods: </strong>RBCs were phenotyped by standard serology methods. The full coding regions of the ABO gene and the erythroid cell-specific regulatory elements in intron one were sequenced. The effect of the possible splice site variant was predicted by Alamut software. The 3D structural modeling of three relative B(A) enzymes (p.Met214Thr, p.Met214Val, and p.Met214Leu) were performed by PyMOL software.</p><p><strong>Results: </strong>Four novel ABO alleles were identified with weak ABO expression in this study, in which two would lead to premature terminations, and two resulted in amino acid changes. In silico analysis revealed that the splice site variant c.155G>T had the potential to alter splice transcripts. 3D structural view shown that the variant amino acid position 214 was spatially adjacent to the donor recognition pocket residues (266Met and 268Ala) and just next to the <sup>211</sup>DVD<sup>213</sup> motif. The size of the side chain of Thr and Val is the smallest, Leu is medium, and Met is the largest, and the size changes in the critical position 214 may affect the donor recognition pocket.</p><p><strong>Conclusion: </strong>Four ABO subgroup alleles were newly linked to different kinds of ABO variants and the possible mechanism through which they produce weak ABO subgroups was analyzed in silico.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":"2364-2370"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Clinical application of centrifugal-membrane hybrid plasmapheresis in the treatment of hyperlipidemia. 离心-膜混合血浆置换术在治疗高脂血症中的临床应用。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-09 DOI: 10.1111/trf.18046
Zhongmei Yi, Chunxi Wu, Yumeng Zhou, Bin Zhang

Objective: This study aimed to clarify the clinical application of centrifugal-membrane hybrid plasmapheresis (CMHP) in the treatment of hyperlipidemia.

Methods: A retrospective study was conducted on 48 patients who were diagnosed with hyperlipidemia and had received CMHP treatment. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were monitored, and adverse reactions to the treatment were observed.

Results: Forty-eight patients with hyperlipidemia received CMHP over 59 sessions. The average age of the 48 patients with hyperlipidemia, including 32 males (66.67%) and 16 females (33.33%), was 44.23 ± 12.02 years. Twenty-nine outpatients (60.42%) and 19 inpatients (39.58%) were included. Hypertriglyceridemia was diagnosed in 16 cases (33.33%), mixed hyperlipidemia in 31 cases (64.58%), and hypercholesterolemia in one case (2.08%). The pretreatment blood lipid concentrations were significantly different after the 59 CMHP treatments (p < .001). The concentrations of TC, TG, HDL-C, and LDL-C decreased significantly after the treatment, and the median ratios of reduction were 67.06% (range: 58.97%-71.87%), 63.33% (range: 55.20%-74.86%), 45.87% (range: 35.86%-52.95%), and 66.09% (range: 44.37%-73.94%), respectively. Three adverse reactions (5.08%) were recorded. No differences were detected in therapeutic parameters, effects, or adverse reactions between the two blood cell separators, there was no difference in Lipoprotein apheresis efficacy.

Conclusion: This preliminary study demonstrated the clinical application of CMHP in patients in the treatment of hyperlipidemia. However, further studies are needed applying CMHP with hyperlipidemia.

研究目的本研究旨在明确离心-膜混合血浆置换术(CMHP)在治疗高脂血症中的临床应用:方法:对 48 例确诊为高脂血症并接受过 CMHP 治疗的患者进行回顾性研究。监测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C),并观察治疗的不良反应:48 名高脂血症患者接受了 CMHP 59 次治疗。48 名高脂血症患者的平均年龄为 44.23±12.02 岁,其中男性 32 人(66.67%),女性 16 人(33.33%)。其中门诊患者 29 人(60.42%),住院患者 19 人(39.58%)。16例(33.33%)被诊断为高甘油三酯血症,31例(64.58%)被诊断为混合型高脂血症,1例(2.08%)被诊断为高胆固醇血症。经过 59 次 CMHP 治疗后,治疗前的血脂浓度有明显差异(P 结论:CMHP 是一种治疗高脂血症的新方法:这项初步研究证明了 CMHP 在治疗高脂血症患者中的临床应用。然而,还需要对 CMHP 在高脂血症中的应用进行进一步研究。
{"title":"Clinical application of centrifugal-membrane hybrid plasmapheresis in the treatment of hyperlipidemia.","authors":"Zhongmei Yi, Chunxi Wu, Yumeng Zhou, Bin Zhang","doi":"10.1111/trf.18046","DOIUrl":"10.1111/trf.18046","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to clarify the clinical application of centrifugal-membrane hybrid plasmapheresis (CMHP) in the treatment of hyperlipidemia.</p><p><strong>Methods: </strong>A retrospective study was conducted on 48 patients who were diagnosed with hyperlipidemia and had received CMHP treatment. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were monitored, and adverse reactions to the treatment were observed.</p><p><strong>Results: </strong>Forty-eight patients with hyperlipidemia received CMHP over 59 sessions. The average age of the 48 patients with hyperlipidemia, including 32 males (66.67%) and 16 females (33.33%), was 44.23 ± 12.02 years. Twenty-nine outpatients (60.42%) and 19 inpatients (39.58%) were included. Hypertriglyceridemia was diagnosed in 16 cases (33.33%), mixed hyperlipidemia in 31 cases (64.58%), and hypercholesterolemia in one case (2.08%). The pretreatment blood lipid concentrations were significantly different after the 59 CMHP treatments (p < .001). The concentrations of TC, TG, HDL-C, and LDL-C decreased significantly after the treatment, and the median ratios of reduction were 67.06% (range: 58.97%-71.87%), 63.33% (range: 55.20%-74.86%), 45.87% (range: 35.86%-52.95%), and 66.09% (range: 44.37%-73.94%), respectively. Three adverse reactions (5.08%) were recorded. No differences were detected in therapeutic parameters, effects, or adverse reactions between the two blood cell separators, there was no difference in Lipoprotein apheresis efficacy.</p><p><strong>Conclusion: </strong>This preliminary study demonstrated the clinical application of CMHP in patients in the treatment of hyperlipidemia. However, further studies are needed applying CMHP with hyperlipidemia.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":"2345-2352"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Identification of two novel variants, c.-35A>T and c.[-35A>T, 725T>G], in the FUT1 gene in a patient exhibiting the para-Bombay phenotype. 在一名表现出准孟买表型的患者体内发现 FUT1 基因中的两个新型变异体:c.-35A>T 和 c.[-35A>T, 725T>G]。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI: 10.1111/trf.18053
Kamphon Intharanut, Piyathida Khumsuk, Sarisa Chidtrakoon, Kantaphon Glab-Ampai, Oytip Nathalang

Background: Reduced or absent H antigens on red cells with the (para-)Bombay phenotype can arise from FUT1 gene mutations, impacting the structure and function of 1,2-L-fucosyltransferase 1 (1,2-L-FucT1). Here, we identified the novel mutations in one patient displaying the para-Bombay phenotype and examined the potential molecular mechanisms underlying this phenotype.

Materials and methods: ABH antigens and antibodies were detected in patient's blood and saliva using serological methods. The genotypes of ABO, FUT1, and FUT2 were imputed using the genetic variations discovered in the whole exome sequencing data. Three-dimensional (3D) models of FUT1 variants were built using Deepmind's AlphaFold2 and HDOCK, and the possible effects of the variants were predicted to evaluate using DynaMut2 and Polyphen-2.

Results: Serological analysis confirmed the para-Bombay B phenotype producing anti-HI and exhibiting normal genotypes ABO*B.01/O.01.02 and FUT2*01.09/01.09. Remarkably, the phenotype is caused by a compound heterozygous genotype: one allele containing the novel c.-35A>T mutation and the known c.725T>G mutation (p.Leu242Arg) of FUT1, and the other allele containing the c.-35A>T mutation. From the computerized stimulation analysis, p.Arg242 of the FUT1 variant may be detrimental, destabilizing, and probably damaging to 1,2-L-FucT1, although not altering the 3D structure of the entire enzyme. The c.-35A>T promoter DNA left at the binding interface of both ZID and c-Rel transcription factors may enable regulation of 1,2-L-FucT1 function at gene promoters.

Conclusion: We identified the two novel variants, c.-35A>T and c.[-35A>T, 725T>G], in the FUT1 causing the para-Bombay phenotype. This finding may clarify the molecular mechanisms and enhance blood transfusion safety.

背景:FUT1基因突变会影响1,2-L-岩藻糖基转移酶1(1,2-L-FucT1)的结构和功能,从而导致(副)孟买表型红细胞上的H抗原减少或缺失。在此,我们确定了一名显示副孟买表型的患者的新型突变,并研究了这种表型的潜在分子机制:采用血清学方法检测患者血液和唾液中的 ABH 抗原和抗体。利用全外显子组测序数据中发现的基因变异来推算 ABO、FUT1 和 FUT2 的基因型。利用 Deepmind 的 AlphaFold2 和 HDOCK 建立了 FUT1 变异的三维(3D)模型,并利用 DynaMut2 和 Polyphen-2 预测评估了变异的可能影响:血清学分析证实,副孟买B表型产生抗-HI,基因型ABO*B.01/O.01.02和FUT2*01.09/01.09正常。值得注意的是,这种表型是由复合杂合基因型引起的:一个等位基因含有 FUT1 的新型 c.-35A>T 突变和已知的 c.725T>G 突变(p.Leu242Arg),另一个等位基因含有 c.-35A>T 突变。从计算机刺激分析来看,FUT1 变体中的 p.Arg242 可能对 1,2-L-FucT1有害,破坏其稳定性,并可能造成损害,尽管不会改变整个酶的三维结构。在ZID和c-Rel转录因子的结合界面上留下的c.-35A>T启动子DNA可能使1,2-L-FucT1的功能在基因启动子上得到调控:我们在 FUT1 中发现了两个新变异,c.-35A>T 和 c.[-35A>T,725T>G],这两个变异导致了副孟买表型。这一发现可能会阐明分子机制并提高输血安全性。
{"title":"Identification of two novel variants, c.-35A>T and c.[-35A>T, 725T>G], in the FUT1 gene in a patient exhibiting the para-Bombay phenotype.","authors":"Kamphon Intharanut, Piyathida Khumsuk, Sarisa Chidtrakoon, Kantaphon Glab-Ampai, Oytip Nathalang","doi":"10.1111/trf.18053","DOIUrl":"10.1111/trf.18053","url":null,"abstract":"<p><strong>Background: </strong>Reduced or absent H antigens on red cells with the (para-)Bombay phenotype can arise from FUT1 gene mutations, impacting the structure and function of 1,2-L-fucosyltransferase 1 (1,2-L-FucT1). Here, we identified the novel mutations in one patient displaying the para-Bombay phenotype and examined the potential molecular mechanisms underlying this phenotype.</p><p><strong>Materials and methods: </strong>ABH antigens and antibodies were detected in patient's blood and saliva using serological methods. The genotypes of ABO, FUT1, and FUT2 were imputed using the genetic variations discovered in the whole exome sequencing data. Three-dimensional (3D) models of FUT1 variants were built using Deepmind's AlphaFold2 and HDOCK, and the possible effects of the variants were predicted to evaluate using DynaMut2 and Polyphen-2.</p><p><strong>Results: </strong>Serological analysis confirmed the para-Bombay B phenotype producing anti-HI and exhibiting normal genotypes ABO*B.01/O.01.02 and FUT2*01.09/01.09. Remarkably, the phenotype is caused by a compound heterozygous genotype: one allele containing the novel c.-35A>T mutation and the known c.725T>G mutation (p.Leu242Arg) of FUT1, and the other allele containing the c.-35A>T mutation. From the computerized stimulation analysis, p.Arg242 of the FUT1 variant may be detrimental, destabilizing, and probably damaging to 1,2-L-FucT1, although not altering the 3D structure of the entire enzyme. The c.-35A>T promoter DNA left at the binding interface of both ZID and c-Rel transcription factors may enable regulation of 1,2-L-FucT1 function at gene promoters.</p><p><strong>Conclusion: </strong>We identified the two novel variants, c.-35A>T and c.[-35A>T, 725T>G], in the FUT1 causing the para-Bombay phenotype. This finding may clarify the molecular mechanisms and enhance blood transfusion safety.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":"2252-2259"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Comparison of the efficacy of a generic plerixafor versus Mozobil as adjunct peripheral blood stem cell mobilization agents in multiple myeloma patients. 多发性骨髓瘤患者辅助外周血干细胞动员剂普乐沙福与莫佐比的疗效比较。
IF 2.5 3区 医学 Q2 HEMATOLOGY Pub Date : 2024-12-01 Epub Date: 2024-10-04 DOI: 10.1111/trf.18033
Shan Yuan, Shelley Chang, Hoim Kim, Shirong Wang

Background: Plerixafor is an adjunct peripheral blood stem cell (PBSC) mobilization agent with well-demonstrated safety and efficacy. The routine use of the originator brand drug (Mozobil) has been limited by cost. This retrospective study was conducted to compare the mobilization efficacy of a lower-cost generic plerixafor and Mozobil in multiple myeloma (MM) patients.

Study design and methods: The study included two near-concurrent cohorts of MM patients mobilized with brand (n = 64) or generic (n = 61) plerixafor in addition to filgrastim. Collection and early engraftment outcomes were compared.

Results: The two cohorts had comparable distributions of sex, age, and weight. Previous treatment histories and proportions of upfront versus just-in-time plerixafor use were similar. There was no significant difference in their median overall cumulative total yield (106 CD34+ cells/kg) (brand, 5.91; generic, 5.80; p = .51). However, the generic cohort had a significantly higher median yield after the first dose (4.79 vs. 3.78, p = .03), and consequently lower median numbers of plerixafor doses (p = .001) and collection days (p = .002). Only 31.1% of patients in the generic arm required more than one dose versus 59.4% of patients in the brand arm (p = .006). All transplanted patients in the brand and generic arms (90.6% and 85.2% respectively, p = .42) achieved engraftment. There was no significant difference in their median times to platelet and neutrophil engraftment, nor their transfusion requirements during the first 30 days post-transplant.

Conclusion: The generic plerixafor produced comparable cumulative collection yields and early engraftment outcomes as Mozobil, but fewer doses and collection days were needed to reach collection goal.

背景介绍普乐沙福是一种辅助性外周血干细胞(PBSC)动员剂,其安全性和有效性已得到充分证明。原研品牌药物(Mozobil)的常规使用一直受到成本的限制。这项回顾性研究旨在比较成本较低的普乐沙福和Mozobil对多发性骨髓瘤(MM)患者的动员疗效:研究包括两组几乎同时使用品牌(n = 64)或非专利(n = 61)plerixafor和filgrastim的MM患者。对采集结果和早期移植结果进行了比较:结果:两组患者的性别、年龄和体重分布相当。既往治疗史以及前期使用和适时使用普乐沙福的比例相似。两者的中位累积总产量(106 个 CD34+ 细胞/千克)无明显差异(品牌:5.91;非专利:5.80;P = .51)。然而,非专利药组首次用药后的中位得率明显更高(4.79 对 3.78,p = .03),因此普乐沙福用药剂量(p = .001)和采集天数(p = .002)的中位数也更低。只有31.1%的非专利组患者需要服用一次以上的剂量,而品牌组则有59.4%的患者需要服用一次以上的剂量(p = .006)。品牌组和非专利组的所有移植患者(分别为 90.6% 和 85.2%,p = .42)都实现了移植。他们的血小板和中性粒细胞移植中位时间以及移植后前30天的输血需求均无明显差异:结论:普通plerixafor的累积采集率和早期移植结果与Mozobil相当,但达到采集目标所需的剂量和采集天数更少。
{"title":"Comparison of the efficacy of a generic plerixafor versus Mozobil as adjunct peripheral blood stem cell mobilization agents in multiple myeloma patients.","authors":"Shan Yuan, Shelley Chang, Hoim Kim, Shirong Wang","doi":"10.1111/trf.18033","DOIUrl":"10.1111/trf.18033","url":null,"abstract":"<p><strong>Background: </strong>Plerixafor is an adjunct peripheral blood stem cell (PBSC) mobilization agent with well-demonstrated safety and efficacy. The routine use of the originator brand drug (Mozobil) has been limited by cost. This retrospective study was conducted to compare the mobilization efficacy of a lower-cost generic plerixafor and Mozobil in multiple myeloma (MM) patients.</p><p><strong>Study design and methods: </strong>The study included two near-concurrent cohorts of MM patients mobilized with brand (n = 64) or generic (n = 61) plerixafor in addition to filgrastim. Collection and early engraftment outcomes were compared.</p><p><strong>Results: </strong>The two cohorts had comparable distributions of sex, age, and weight. Previous treatment histories and proportions of upfront versus just-in-time plerixafor use were similar. There was no significant difference in their median overall cumulative total yield (10<sup>6</sup> CD34+ cells/kg) (brand, 5.91; generic, 5.80; p = .51). However, the generic cohort had a significantly higher median yield after the first dose (4.79 vs. 3.78, p = .03), and consequently lower median numbers of plerixafor doses (p = .001) and collection days (p = .002). Only 31.1% of patients in the generic arm required more than one dose versus 59.4% of patients in the brand arm (p = .006). All transplanted patients in the brand and generic arms (90.6% and 85.2% respectively, p = .42) achieved engraftment. There was no significant difference in their median times to platelet and neutrophil engraftment, nor their transfusion requirements during the first 30 days post-transplant.</p><p><strong>Conclusion: </strong>The generic plerixafor produced comparable cumulative collection yields and early engraftment outcomes as Mozobil, but fewer doses and collection days were needed to reach collection goal.</p>","PeriodicalId":23266,"journal":{"name":"Transfusion","volume":" ","pages":"2332-2340"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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