British Journal of Haematology最新文献_第9页

Acalabrutinib in combination with rituximab and lenalidomide in patients with relapsed or refractory follicular lymphoma: Results of the phase 1b open-label study (ACE-LY-003). 阿卡拉布替尼联合利妥昔单抗和来那度胺治疗复发或难治性滤泡性淋巴瘤：1b期开放标签研究（ACE-LY-003）的结果

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-12 DOI: 10.1111/bjh.19951

Paolo Strati, Richy Agajanian, Izidore S Lossos, Morton Coleman, Robert Kridel, Andrew Wood, Robin Lesley, Chuan-Chuan Wun, Deborah M Stephens

{"title":"Acalabrutinib in combination with rituximab and lenalidomide in patients with relapsed or refractory follicular lymphoma: Results of the phase 1b open-label study (ACE-LY-003).","authors":"Paolo Strati, Richy Agajanian, Izidore S Lossos, Morton Coleman, Robert Kridel, Andrew Wood, Robin Lesley, Chuan-Chuan Wun, Deborah M Stephens","doi":"10.1111/bjh.19951","DOIUrl":"https://doi.org/10.1111/bjh.19951","url":null,"abstract":"Patients with relapsed/refractory (R/R) follicular lymphoma (FL) have limited effective treatment options. Bruton tyrosine kinase inhibitors (BTKis) increase the anti-tumoural phenotype of tumour-associated macrophages, providing rationale to combine them with rituximab and lenalidomide (R2). Acalabrutinib, a second-generation BTKi, has potential to improve R2 efficacy without increasing T-cell-mediated toxicity due to its lack of interleukin-2-inducible T-cell kinase inhibition. Here, we report safety and efficacy from a phase 1b dose-finding study (NCT02180711) evaluating acalabrutinib plus R2 in patients with R/R FL. Overall, 29 patients received acalabrutinib plus R2 (lenalidomide 15 mg, n = 8; lenalidomide 20 mg, n = 21). At a median acalabrutinib exposure of 21 months, the most common grade ≥3 treatment-emergent adverse event (TEAE) was neutropenia (37.9%). The incidence of grade ≥3 serious TEAEs was 37.5% and 52.4% in the lenalidomide 15-mg and 20-mg cohorts, respectively; overall, the most common were COVID-19 pneumonia, COVID-19 infection and pneumonia. Earlier treatment withholdings/reductions were observed in the 20-mg cohort. With a median follow-up of 34.1 months, the overall response rate was 75.9%. The complete response rate was 25.0% and 42.9% in the lenalidomide 15- and 20-mg cohorts, respectively. Due to acceptable toxicity and preliminary efficacy, the lenalidomide 20-mg dose was selected for further investigation.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Chimeric antigen receptor copies in cell-free DNA predict relapse in aggressive B-cell lymphoma patients treated with CAR T-cell therapy 细胞游离 DNA 中的嵌合抗原受体拷贝可预测接受 CAR T 细胞疗法的侵袭性 B 细胞淋巴瘤患者的复发。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-12 DOI: 10.1111/bjh.19916

Ismael de la Iglesia-San Sebastián, Miguel López-Esteban, Mariana Bastos-Oreiro, Sara Fernández de Córdoba-Oñate, Maravillas Gutierrez, Diego Carbonell, Rebeca Bailén, Ignacio Gómez-Centurión, Paula Fernández-Caldas, Lucía Castilla, Javier Anguita, Mi Kwon, Ramón García-Sanz, Ismael Buño, Carolina Martínez-Laperche

{"title":"Chimeric antigen receptor copies in cell-free DNA predict relapse in aggressive B-cell lymphoma patients treated with CAR T-cell therapy","authors":"Ismael de la Iglesia-San Sebastián, Miguel López-Esteban, Mariana Bastos-Oreiro, Sara Fernández de Córdoba-Oñate, Maravillas Gutierrez, Diego Carbonell, Rebeca Bailén, Ignacio Gómez-Centurión, Paula Fernández-Caldas, Lucía Castilla, Javier Anguita, Mi Kwon, Ramón García-Sanz, Ismael Buño, Carolina Martínez-Laperche","doi":"10.1111/bjh.19916","DOIUrl":"10.1111/bjh.19916","url":null,"abstract":"<div>\u0000 \u0000 Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for aggressive B-cell lymphomas (ABCL), However, about half of patients relapse, most of them early. This study investigates the detection of CAR copies in circulating cell-free DNA (cfDNA) as a potential predictive biomarker of early relapse (<6 months) to improve patient management. In this research, we have consecutively selected 73 ABCL patients treated with anti-CD19 CAR T-cells, analysing CAR levels in peripheral blood and other clinical variables. Our results indicate that no correlation is present between genomic DNA and cfDNA; moreover, higher levels of CAR-cfDNA on day +14 after infusion (0.44 vs. 0.07; p = 0.019) are associated with improved 6-month progression-free survival rates (74.2% vs. 26%. p < 0.01), suggesting that CAR-cfDNA could be a strong predictor of CAR T-cell therapy short-term outcomes. These findings underscore the potential of integrating CAR-cfDNA analysis into routine clinical practice to enhance the prognostic accuracy and therapeutic strategies for ABCL patients undergoing CAR T-cell therapy.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"206 1","pages":"195-203"},"PeriodicalIF":5.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Development and validation of a deep learning model for morphological assessment of myeloproliferative neoplasms using clinical data and digital pathology 利用临床数据和数字病理学对骨髓增生性肿瘤进行形态学评估的深度学习模型的开发和验证。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-10 DOI: 10.1111/bjh.19938

Rong Wang, Zhongxun Shi, Yuan Zhang, Liangmin Wei, Minghui Duan, Min Xiao, Jin Wang, Suning Chen, Qian Wang, Jianyao Huang, Xiaomei Hu, Jinhong Mei, Jieyu He, Feng Chen, Lei Fan, Guanyu Yang, Wenyi Shen, Yongyue Wei, Jianyong Li

{"title":"Development and validation of a deep learning model for morphological assessment of myeloproliferative neoplasms using clinical data and digital pathology","authors":"Rong Wang, Zhongxun Shi, Yuan Zhang, Liangmin Wei, Minghui Duan, Min Xiao, Jin Wang, Suning Chen, Qian Wang, Jianyao Huang, Xiaomei Hu, Jinhong Mei, Jieyu He, Feng Chen, Lei Fan, Guanyu Yang, Wenyi Shen, Yongyue Wei, Jianyong Li","doi":"10.1111/bjh.19938","DOIUrl":"10.1111/bjh.19938","url":null,"abstract":"The subjectivity of morphological assessment and the overlapping pathological features of different subtypes of myeloproliferative neoplasms (MPNs) make accurate diagnosis challenging. To improve the pathological assessment of MPNs, we developed a diagnosis model (fusion model) based on the combination of bone marrow whole-slide images (deep learning [DL] model) and clinical parameters (clinical model). Thousand and fifty-one MPN and non-MPN patients were divided into the training, internal testing and one internal and two external validation cohorts (the combined validation cohort). In the combined validation cohort, fusion model achieved higher areas under curve (AUCs) than clinical or DL model or both for MPNs and subtype identification. Compared with haematopathologists with different experience, clinical model achieved AUC which was comparable to seniors and higher than juniors (p = 0.0208) for polycythaemia vera. The AUCs of fusion model were comparable to seniors and higher than juniors for essential thrombocytosis (p = 0.0141), prefibrotic primary myelofibrosis (p = 0.0085) and overt primary myelofibrosis (p = 0.0330) identification. In conclusion, the performances of our proposed models are equivalent to senior haematopathologists and better than juniors, providing a new perspective on the utilization of DL algorithms in MPN morphological assessment.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"206 2","pages":"596-606"},"PeriodicalIF":5.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Imaging flow cytometry as a novel approach for the diagnosis of heparin-induced thrombocytopenia 成像流式细胞术作为诊断肝素诱导的血小板减少症的新方法。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-10 DOI: 10.1111/bjh.19945

Julie Carré, Yohann Demont, Christine Mouton, Caroline Vayne, Eve-Anne Guéry, Annelise Voyer, Loïc Garçon, Maïlys Le Guyader, Julien Demagny

{"title":"Imaging flow cytometry as a novel approach for the diagnosis of heparin-induced thrombocytopenia","authors":"Julie Carré, Yohann Demont, Christine Mouton, Caroline Vayne, Eve-Anne Guéry, Annelise Voyer, Loïc Garçon, Maïlys Le Guyader, Julien Demagny","doi":"10.1111/bjh.19945","DOIUrl":"10.1111/bjh.19945","url":null,"abstract":"Heparin-induced thrombocytopenia (HIT) is an adverse reaction characterized by anti-PF4-heparin antibody generation and hypercoagulability. Imaging flow cytometry (IFC) provides a detailed morphological analysis of platelets, which change upon activation. We evaluated IFC-derived morphometric features to detect platelet activation and developed a functional assay for HIT diagnosis. We analysed blood samples from 42 patients with suspected HIT and extracted platelet size, shape and texture features using IFC. The morphological features were compared with CD62P expression, light transmission aggregometry (LTA) and a serotonin release assay (SRA) in terms of their ability to predict a HIT diagnosis. Five IFC-derived morphological features (area, circularity, contrast, diameter and major axis) significantly distinguished resting from activated platelets. The major axis feature performed best for HIT diagnosis, with a sensitivity of 89.3% and a specificity of 92.9% versus functional assays (LTA/SRA); this diagnostic performance was similar to that of CD62P expression on the same platelet donors. The area and diameter had similar specificity (92.9%) and a slightly lower sensitivity (85.7%). The morphological features associated with platelet activation might be effective markers for the diagnosis of HIT, matching platelet CD62P expression assay performance. The high-throughput IFC exploration of platelet activation offers new perspectives in label-free analysis and time-saving.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"206 2","pages":"666-674"},"PeriodicalIF":5.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19945","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Development of a novel test of splenic function for use in a clinical diagnostic laboratory 用于临床诊断实验室的一种新的脾功能测试的发展。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-10 DOI: 10.1111/bjh.19950

Azalea A. Khan, Claire E. Laas, John N. Brewin, Victoria Potter, Huan Cao, Mark A. Vickers, Barnaby Clark, David C. Rees

{"title":"Development of a novel test of splenic function for use in a clinical diagnostic laboratory","authors":"Azalea A. Khan, Claire E. Laas, John N. Brewin, Victoria Potter, Huan Cao, Mark A. Vickers, Barnaby Clark, David C. Rees","doi":"10.1111/bjh.19950","DOIUrl":"10.1111/bjh.19950","url":null,"abstract":"<div>\u0000 \u0000 The spleen is prone to both physical damage and functional impairment, which can be difficult to detect before catastrophic complications occur. Currently available tests of splenic function are laborious, user-dependent and unreliable, so there is an unmet need for a reliable test offered routinely in diagnostic laboratories. In this study, we have assessed a simple flow cytometry-based method measuring high mannose glycans (HMGs) on erythrocytes, which has previously been proposed as a potential test of splenic function. We developed the test as a diagnostic assay using blood from a range of control and potentially hyposplenic samples, including people with sickle cell disease. HMG expression correlated well with manual pit counting, an established method for assessing splenic function (r = 0.6). A threshold of >36% difference compared to the mean of control samples was used to define hyposplenism. At this threshold, the test is 93% sensitive and 100% specific for detecting splenic dysfunction. The test was highly reproducible and stable in blood samples of up to 4 days old. This test is non-invasive with quantitative data output and requires significantly less operator time than other available techniques, making it a robust new clinical assay for determining splenic function.\u0000 </div>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"206 1","pages":"320-330"},"PeriodicalIF":5.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis 追求治疗干预和克隆造血早期临床试验的蓝图。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-09 DOI: 10.1111/bjh.19925

Tamanna Haque, Aditi Shastri, Pinkal Desai, Zhuoer Xie, Danielle Hammond, Zoe King, Ashwin Kishtagari, Yazan F. Madanat, Yasmin Abaza, Alexander J. Silver, Abhay Singh, Uma M. Borate, J. Brett Heimlich, David A. Slosky, Kelly L. Bolton, Mrinal S. Patnaik, Alexander G. Bick, Amit K. Verma, Siddhartha Jaiswal, David P. Steensma, Michael R. Savona

{"title":"A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis","authors":"Tamanna Haque, Aditi Shastri, Pinkal Desai, Zhuoer Xie, Danielle Hammond, Zoe King, Ashwin Kishtagari, Yazan F. Madanat, Yasmin Abaza, Alexander J. Silver, Abhay Singh, Uma M. Borate, J. Brett Heimlich, David A. Slosky, Kelly L. Bolton, Mrinal S. Patnaik, Alexander G. Bick, Amit K. Verma, Siddhartha Jaiswal, David P. Steensma, Michael R. Savona","doi":"10.1111/bjh.19925","DOIUrl":"10.1111/bjh.19925","url":null,"abstract":"The age-associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy. Thoughtful consideration is needed to design trials that are both clinically relevant and avoid overmedicalization. Here, we summarize clinical studies of CH to date and provide suggestions and guidance on how to approach designing CH-focused therapeutic clinical trials. These recommendations are derived from discussions among clinical researchers and scientists emanating from the Inaugural Meeting on Somatic Mutations and Predisease in October 2021.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":"206 2","pages":"416-427"},"PeriodicalIF":5.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.19925","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Service evaluation of R90 bleeding and platelet disorders gene panel in thrombocytopenia cases. 血小板减少症患者R90出血与血小板紊乱基因检测的价值评价。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-09 DOI: 10.1111/bjh.19947

G Gurumurthy, L Reynolds, M Sutherland, J Thachil, J Grainger

引用次数: 0

Drafting a blueprint for designing successful clinical trials in clonal haematopoiesis 为克隆造血的成功临床试验起草蓝图。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-09 DOI: 10.1111/bjh.19948

Shyam A. Patel, Lachelle D. Weeks

引用次数: 0

Fatal thrombotic microangiopathy during induction for acute myeloid leukemia: A case report and review of vascular complications in germline GATA2 haploinsufficiency 急性髓系白血病诱导过程中致死性血栓性微血管病变：种系GATA2单倍性不全血管并发症一例报告及回顾。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-08 DOI: 10.1111/bjh.19935

Erin L. Frost, Satheesh Chonat, Kirsten M. Williams, Waitman Aumann, Jason Stevenson, Julie Yin, Michael Schniederjan, Staci Arnold, Michelle L. Schoettler

引用次数: 0

Low-dose iron chelation as anti-oxidative therapy in patients with sickle cell disease: A single-centre pilot study. 低剂量铁螯合作为镰状细胞病患者的抗氧化治疗：一项单中心试点研究

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-12-06 DOI: 10.1111/bjh.19943

Aafke E Gaartman, Boukje M Beuger, Lydian A de Ligt, Martijn Veldthuis, Hanke L Matlung, Joost C M Meijers, Casper G Schalkwijk, Koen de Heer, Jarom Heijmans, Rob van Zwieten, Bart J Biemond, Robin van Bruggen, Erfan Nur

引用次数: 0