IF 21 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2023023660

Leslie S Kean, Linda J Burns, Tzuyung D Kou, Roxanne Kapikian, Karissa Lozenski, Amelia Langston, John T Horan, Benjamin Watkins, Muna Qayed, Brandi Bratrude, Kayla Betz, Xiao-Ying Tang, Mei-Jie Zhang, Sean E Connolly, Martin Polinsky, Brian Gavin, Andres Gomez-Caminero, Marcelo C Pasquini

{"title":"Abatacept for acute graft-versus-host disease prophylaxis after unrelated donor hematopoietic cell transplantation.","authors":"Leslie S Kean, Linda J Burns, Tzuyung D Kou, Roxanne Kapikian, Karissa Lozenski, Amelia Langston, John T Horan, Benjamin Watkins, Muna Qayed, Brandi Bratrude, Kayla Betz, Xiao-Ying Tang, Mei-Jie Zhang, Sean E Connolly, Martin Polinsky, Brian Gavin, Andres Gomez-Caminero, Marcelo C Pasquini","doi":"10.1182/blood.2023023660","DOIUrl":"10.1182/blood.2023023660","url":null,"abstract":"Abstract: Abatacept plus calcineurin inhibitors/methotrexate (CNI/MTX) is the first US Food and Drug Administration (FDA)-approved regimen for acute graft-versus-host disease (aGVHD) prophylaxis during unrelated-donor hematopoietic cell transplantation (URD-HCT). Using Center for International Blood and Marrow Transplant Research data, we investigated its impact in patients receiving 7/8 HLA-mismatched unrelated donor (MMUD) or 8/8 HLA-matched unrelated donor (MUD) URD-HCT between 2011 and 2018. Primary outcomes included day-180, 1-year, and 2-year overall survival (OS) and relapse-free survival (RFS) for abatacept + CNI/MTX vs CNI/MTX, CNI/MTX + antithymocyte globulin (ATG), and posttransplant cyclophosphamide-based prophylaxis (PT-Cy). For 7/8 MMUDs, day-180 OS (primary end point supporting FDA approval) was significantly higher for abatacept + CNI/MTX vs CNI/MTX (98% vs 75%; P = .0028). Two-year RFS was significantly higher for abatacept + CNI/MTX vs CNI/MTX (74% vs 49%; P = .0098) and CNI/MTX + ATG (77% vs 35%; P = .0002), and similar vs PT-Cy (72% vs 56%; P = .1058). For 8/8 MUDs, 2-year RFS for abatacept + CNI/MTX was numerically higher vs CNI/MTX (63% vs 52%; P = .1497), with an improved hazard ratio (HR) of 0.46 (0.25-0.86), and vs CNI/MTX + ATG (66% vs 55%; P = .1193; HR, 0.39 [0.21-0.73]), and was similar vs PT-Cy (68% vs 57%; P = .2356; HR, 0.54 [0.26-1.11]). For 7/8 MMUD and 8/8 MUD recipients, abatacept + CNI/MTX prophylaxis improved survival outcomes vs CNI/MTX and CNI/MTX + ATG; outcomes were similar to PT-Cy-based regimens. Abatacept + CNI/MTX may facilitate unrelated donor pool expansion for HCT.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1834-1845"},"PeriodicalIF":21.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Barrier disruption by coagulation FXIa. 凝血 FXIa 对屏障的破坏。

IF 21 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024026283

Philip Wenzel, Wolfram Ruf

引用次数: 0

Catch 'em all! CDK9's RUNX1 mega evolution. 一网打尽！CDK9 的 RUNX1 巨型进化。

IF 20.3 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024026377

Ashley P Ng

引用次数: 0

Proposals for revised International Working Group-European LeukemiaNet criteria for anemia response in myelofibrosis. 国际工作组-欧洲白血病网络骨髓纤维化贫血反应标准修订提案。

IF 21 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024025802

Ayalew Tefferi, Giovanni Barosi, Francesco Passamonti, Juan-Carlos Hernandez-Boluda, Prithviraj Bose, Konstanze Döhner, Martin Ellis, Naseema Gangat, Jacqueline S Garcia, Heinz Gisslinger, Jason Gotlib, Paola Guglielmelli, Vikas Gupta, Claire Harrison, Elizabeth O Hexner, Gabriela S Hobbs, Jean-Jacques Kiladjian, Steffen Koschmieder, Nicolaus Kroger, Andrew T Kuykendall, Giuseppe G Loscocco, John Mascarenhas, Lucia Masarova, Ruben Mesa, Barbara Mora, Olatoyosi Odenike, Stephen T Oh, Animesh Pardanani, Anand Patel, Naveen Pemmaraju, Alessandro Rambaldi, Raajit Rampal, Shireen Sirhan, Natasha Szuber, Moshe Talpaz, Pankit J Vachhani, Alessandro M Vannucchi, Tiziano Barbui

{"title":"Proposals for revised International Working Group-European LeukemiaNet criteria for anemia response in myelofibrosis.","authors":"Ayalew Tefferi, Giovanni Barosi, Francesco Passamonti, Juan-Carlos Hernandez-Boluda, Prithviraj Bose, Konstanze Döhner, Martin Ellis, Naseema Gangat, Jacqueline S Garcia, Heinz Gisslinger, Jason Gotlib, Paola Guglielmelli, Vikas Gupta, Claire Harrison, Elizabeth O Hexner, Gabriela S Hobbs, Jean-Jacques Kiladjian, Steffen Koschmieder, Nicolaus Kroger, Andrew T Kuykendall, Giuseppe G Loscocco, John Mascarenhas, Lucia Masarova, Ruben Mesa, Barbara Mora, Olatoyosi Odenike, Stephen T Oh, Animesh Pardanani, Anand Patel, Naveen Pemmaraju, Alessandro Rambaldi, Raajit Rampal, Shireen Sirhan, Natasha Szuber, Moshe Talpaz, Pankit J Vachhani, Alessandro M Vannucchi, Tiziano Barbui","doi":"10.1182/blood.2024025802","DOIUrl":"10.1182/blood.2024025802","url":null,"abstract":"Abstract: With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1813-1820"},"PeriodicalIF":21.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo. 凝血因子 XI 在体外和体内调节内皮细胞的通透性和屏障功能。

IF 21 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2023022257

Cristina Puy, Samantha A Moellmer, Jiaqing Pang, Helen H Vu, Alexander R Melrose, Christina U Lorentz, Erik I Tucker, Joseph J Shatzel, Ravi S Keshari, Florea Lupu, David Gailani, Owen J T McCarty

{"title":"Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo.","authors":"Cristina Puy, Samantha A Moellmer, Jiaqing Pang, Helen H Vu, Alexander R Melrose, Christina U Lorentz, Erik I Tucker, Joseph J Shatzel, Ravi S Keshari, Florea Lupu, David Gailani, Owen J T McCarty","doi":"10.1182/blood.2023022257","DOIUrl":"10.1182/blood.2023022257","url":null,"abstract":"Abstract: Loss of endothelial barrier function contributes to the pathophysiology of many inflammatory diseases. Coagulation factor XI (FXI) plays a regulatory role in inflammation. Although activation of FXI increases vascular permeability in vivo, the mechanism by which FXI or its activated form FXIa disrupts endothelial barrier function is unknown. We investigated the role of FXIa in human umbilical vein endothelial cell (HUVEC) or human aortic endothelial cell (HAEC) permeability. The expression patterns of vascular endothelial (VE)-cadherin and other proteins of interest were examined by western blot or immunofluorescence. Endothelial cell permeability was analyzed by Transwell assay. We demonstrate that FXIa increases endothelial cell permeability by inducing cleavage of the VE-cadherin extracellular domain, releasing a soluble fragment. The activation of a disintegrin and metalloproteinase 10 (ADAM10) mediates the FXIa-dependent cleavage of VE-cadherin, because adding an ADAM10 inhibitor prevented the cleavage of VE-cadherin induced by FXIa. The binding of FXIa with plasminogen activator inhibitor 1 and very low-density lipoprotein receptor on HUVEC or HAEC surfaces activates vascular endothelial growth receptor factor 2 (VEGFR2). The activation of VEGFR2 triggers the mitogen-activated protein kinase (MAPK) signaling pathway and promotes the expression of active ADAM10 on the cell surface. In a pilot experiment using an established baboon model of sepsis, the inhibition of FXI activation significantly decreased the levels of soluble VE-cadherin to preserve barrier function. This study reveals a novel pathway by which FXIa regulates vascular permeability. The effect of FXIa on barrier function may be another way by which FXIa contributes to the development of inflammatory diseases.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1821-1833"},"PeriodicalIF":21.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapies. 对既往接受过≥2种疗法的复发或难治滤泡性淋巴瘤患者进行莫舒珠单抗3年长期随访。

IF 20.3 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024025454

Laurie H Sehn,Nancy L Bartlett,Matthew J Matasar,Stephen J Schuster,Sarit E Assouline,Pratyush Giri,John Kuruvilla,Mazyar Shadman,Chan Y Cheah,Sascha Dietrich,Keith Fay,Matthew Ku,Loretta J Nastoupil,Michael C Wei,Shen Yin,Iris To,Derrick Kaufman,Antonia Kwan,Elicia Penuel,Christopher R Bolen,Lihua Elizabeth Budde

{"title":"Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapies.","authors":"Laurie H Sehn,Nancy L Bartlett,Matthew J Matasar,Stephen J Schuster,Sarit E Assouline,Pratyush Giri,John Kuruvilla,Mazyar Shadman,Chan Y Cheah,Sascha Dietrich,Keith Fay,Matthew Ku,Loretta J Nastoupil,Michael C Wei,Shen Yin,Iris To,Derrick Kaufman,Antonia Kwan,Elicia Penuel,Christopher R Bolen,Lihua Elizabeth Budde","doi":"10.1182/blood.2024025454","DOIUrl":"https://doi.org/10.1182/blood.2024025454","url":null,"abstract":"Mosunetuzumab, a CD20xCD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate (ORR) were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7-not estimable [NE]). Among 54 patients who achieved CR, 49 remained in CR at the end of treatment; median duration of complete response was not reached (NR) (95% CI, 33.0-NE); Kaplan-Meier-estimated 30-month remission rate was 72.4% (95% CI, 59.2-85.6). Estimated 36-month overall survival (OS) rate was 82.4% (95% CI, 73.8-91.0); median OS was NR (95% CI, NE-NE). Median progression-free survival was 24.0 months (95% CI, 12.0-NE). Median time to CD19+ B-cell recovery was 18.4 months (95% CI, 12.8-25.0) following 8 cycles of mosunetuzumab treatment. No new cytokine release syndrome events or fatal, serious, or Grade ≥3 adverse events were reported. With extended follow-up, mosunetuzumab demonstrated high response rates, durable remissions and manageable safety with no long-term concerns. This supports outpatient mosunetuzumab administration as an off-the-shelf, fixed-duration, safe and effective treatment for patients with R/R FL, including those with high-risk disease. Trial registration: www.clinicaltrials.gov (NCT02500407).","PeriodicalId":9102,"journal":{"name":"Blood","volume":"26 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Abatacept vs PT-Cy for GVHD prophylaxis. 阿巴他赛与PT-Cy用于预防GVHD。

IF 20.3 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024026116

Frédéric Baron

引用次数: 0

Anemia response in myelofibrosis revisited. 再论骨髓纤维化的贫血反应

IF 21 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024026393

Ashish Bajel

引用次数: 0

Eltrombopag plus diacerein vs eltrombopag in patients with ITP: a multicenter, randomized, open-label phase 2 trial. 艾曲波帕加迪阿色林与艾曲波帕治疗 ITP 患者：一项多中心、随机、开放标签的 2 期试验。

IF 21 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024025067

Lu Sun, Xiaoyang Huang, Juan Wang, Chenglu Yuan, Hongyu Zhao, Daqi Li, Ruirong Xu, Yan Wang, Ping Qin, Yan Shi, Jun Peng, Ming Hou, Yu Hou

{"title":"Eltrombopag plus diacerein vs eltrombopag in patients with ITP: a multicenter, randomized, open-label phase 2 trial.","authors":"Lu Sun, Xiaoyang Huang, Juan Wang, Chenglu Yuan, Hongyu Zhao, Daqi Li, Ruirong Xu, Yan Wang, Ping Qin, Yan Shi, Jun Peng, Ming Hou, Yu Hou","doi":"10.1182/blood.2024025067","DOIUrl":"10.1182/blood.2024025067","url":null,"abstract":"Abstract: This study aimed to compare the efficacy and safety of eltrombopag plus diacerein vs eltrombopag alone in patients with primary immune thrombocytopenia (ITP) who were previously unresponsive to 14 days of eltrombopag treatment at the full dose. Recruited patients were randomly assigned 1:1 to receive either eltrombopag plus diacerein (n = 50) or eltrombopag monotherapy (n = 52). Overall response rate, defined as a platelet count of ≥30 × 109/L, at least doubling of the baseline platelet count, and no bleeding, was reached in 44% of patients in the eltrombopag plus diacerein group compared with 13% in the eltrombopag group at day 15 (P = .0009), and reached in 42% of patients in the combination group compared with 12% in the monotherapy group at day 28 (P = .0006). The addition of diacerein to eltrombopag also led to a longer duration of response (P = .0004). The 2 most common treatment-emergent adverse events were respiratory infection and gastrointestinal reactions in the combination group, and fatigue and respiratory infection in the eltrombopag group. In conclusion, eltrombopag plus diacerein was well tolerated, and induced higher overall response rates and longer duration of response than eltrombopag alone, offering a rejuvenating salvage therapy for patients with ITP unresponsive to 14 days of full dosage eltrombopag. Our work has the potential to enhance the care of patients treated with thrombopoietin receptor agonists, reducing the need for rapid transitions to less-preferable therapies. This study is registered at ClinicalTrials.gov as #NCT04917679.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1791-1799"},"PeriodicalIF":21.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

ERG: the good, the bad, and the ugly. ERG：好、坏、丑。

IF 20.3 1区医学

Blood Pub Date : 2024-10-24 DOI: 10.1182/blood.2024025898

Ron Rabinowicz,Shai Izraeli

引用次数: 0

Blood最新文献