British Journal of Haematology最新文献

Rates of discordant CD20 status by flow cytometry and immunohistochemistry in B-ALL. 流式细胞术和免疫组化法检测 B-ALL 中 CD20 状态不一致的比率。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-19 DOI: 10.1111/bjh.19909

Samuel Grigg, Melissa Ng Liet Hing, Kah Lok Chan, Surender Juneja, David Westerman

引用次数: 0

Are we there yet? CAR-T therapy in multiple myeloma. 我们成功了吗？多发性骨髓瘤的 CAR-T 疗法

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-19 DOI: 10.1111/bjh.19896

Eitan Mirvis, Reuben Benjamin

{"title":"Are we there yet? CAR-T therapy in multiple myeloma.","authors":"Eitan Mirvis, Reuben Benjamin","doi":"10.1111/bjh.19896","DOIUrl":"https://doi.org/10.1111/bjh.19896","url":null,"abstract":"The last few years have seen a revolution in cellular immunotherapies for multiple myeloma (MM) with novel antigen targets. The principle new target is B-cell maturation antigen (BCMA). Autologous chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA was first approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2021, although approval by the National Institute for Health and Care Excellent (NICE) is awaited. Initial response rates in patients with heavily pretreated MM have been impressive, but patients are still relapsing. Furthermore, CAR-T manufacturing is expensive and time-consuming, and T-cell fitness is impaired by prior MM treatment. Numerous strategies to improve outcomes and delivery of cellular immunotherapy are under investigation, including next-generation CARs, allogeneic 'off-the-shelf' CARs and targeting of other MM antigens including G protein-coupled receptor, class C, group 5, member D (GPRC5D), Fc receptor homologue 5 (FcRH5), cluster of differentiation (CD)19, signalling lymphocyte activation molecule family member 7 (SLAMF7) and several others. In this exciting and rapidly evolving treatment landscape, this review evaluates the most recent clinical and preclinical data pertaining to these new cellular immunotherapies and explores strategies to overcome resistance pathways. On the protracted journey to a long-term cure, we outline the challenges that lie ahead and ask, 'Are we there yet?'","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666489","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

Inhibition of FcRn with rozanolixizumab in adults with immune thrombocytopenia: Two randomised, double-blind, placebo-controlled phase 3 studies and their open-label extension. 罗扎尼单抗抑制免疫性血小板减少症成人患者的 FcRn：两项随机、双盲、安慰剂对照的 3 期研究及其开放标签扩展研究。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-18 DOI: 10.1111/bjh.19858

Nichola Cooper, James B Bussel, Maciej Kaźmierczak, Yoshitaka Miyakawa, Sarah Cluck, Rocío Lledó García, Birgit Haier, Andreea Lavrov, Puneet Singh, Rose Snipes, David J Kuter

{"title":"Inhibition of FcRn with rozanolixizumab in adults with immune thrombocytopenia: Two randomised, double-blind, placebo-controlled phase 3 studies and their open-label extension.","authors":"Nichola Cooper, James B Bussel, Maciej Kaźmierczak, Yoshitaka Miyakawa, Sarah Cluck, Rocío Lledó García, Birgit Haier, Andreea Lavrov, Puneet Singh, Rose Snipes, David J Kuter","doi":"10.1111/bjh.19858","DOIUrl":"https://doi.org/10.1111/bjh.19858","url":null,"abstract":"Primary immune thrombocytopenia (ITP) is an antiplatelet-antibody-mediated disorder with accelerated platelet clearance and decreased platelet production. Rozanolixizumab, a monoclonal IgG4 anti-FcRn antibody, blocks IgG recycling and decreases IgG levels. We report efficacy and safety of rozanolixizumab in adults with persistent/chronic ITP in 24-week phase 3 studies (TP0003; TP0006), and their 52-week open-label extension (OLE). Primary end-point was durable clinically meaningful platelet response (DCMPR) of ≥50 × 109/L for 8/12 weeks during Weeks 13-25 in the double-blind studies. Operational delays and evolving ITP treatment landscape led the sponsor to terminate these studies early; thus, only 21 and 12 (TP0003) and 20 and 10 (TP0006) patients were randomised to rozanolixizumab or placebo. Forty-three patients enrolled in the OLE: 42 started on every 2-week dosing; 21 later switched to weekly dosing. More rozanolixizumab-treated than placebo-treated patients achieved DCMPR: 4/21 versus 0 (TP0003) and 1/20 versus 0 (TP0006). Platelet increases to ≥50 × 109/L were observed on Day 8 in 52.4% (TP0003; 2/12 placebo) and 45.0% (TP0006; 1/10 placebo) of rozanolixizumab-treated patients. OLE platelet increases were maintained while on weekly dosing. The most frequent treatment-emergent adverse events overall were headache, pyrexia and nausea, as seen previously. Weekly dosing appears more efficacious than every 2-week dosing.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646084","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

Somatic co-alteration signatures are prognostic in high-grade TP53-mutated myeloid neoplasms. 体细胞共变异特征对高级别 TP53 突变髓样肿瘤具有预后作用。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-17 DOI: 10.1111/bjh.19895

Emily O Symes, Peng Wang, Payal Sojitra, Madhu P Menon, Anand A Patel, Faheema Hasan, Sharmila Ghosh, Gregory W Roloff, Qianghua Zhou, Anthony Findley, Talha Badar, Jingjing Zhang, Hamza Tariq, Hong Chang, Robert C Bell, Anamarija M Perry, Girish Venkataraman

{"title":"Somatic co-alteration signatures are prognostic in high-grade TP53-mutated myeloid neoplasms.","authors":"Emily O Symes, Peng Wang, Payal Sojitra, Madhu P Menon, Anand A Patel, Faheema Hasan, Sharmila Ghosh, Gregory W Roloff, Qianghua Zhou, Anthony Findley, Talha Badar, Jingjing Zhang, Hamza Tariq, Hong Chang, Robert C Bell, Anamarija M Perry, Girish Venkataraman","doi":"10.1111/bjh.19895","DOIUrl":"https://doi.org/10.1111/bjh.19895","url":null,"abstract":"To assess the relevance of co-occurring somatic mutations in TP53-mutated myeloid neoplasms with ≥10% blasts, we pooled 325 individuals from 10 centres. We focused on comparing three published somatic co-alteration signatures comprising (1) nine MDS-related genes ('ICC-MDSR'), (2) ICC-MDSR + additional secondary mutations-related genes ('Tazi signature') and (3) EPI6 (comprising six genes). Outcomes examined were 24-month overall survival (OS24) and front-line complete response (CR1). The median age was 69 years with 77% receiving front-line hypomethylating agents (HMA). All three signatures ICC-MDSR (p = 0.009), Tazi signature (p = 0.001) and EPI6 (p = 0.025) predicted inferior CR1. In the low-intensity (HMA) subgroup, only Tazi signature (p = 0.026) predicted inferior CR1. In OS24 analysis of the HMA-treated subgroup (N = 200), only Tazi signature was adverse (hazard ratio, HR = 1.6 [1.1-2.2]; p = 0.011). However, a forward stepwise multivariable age-adjusted Cox model including all three signatures picked EPI6 as the sole significant adverse predictor in the entire cohort (p = 0.0001) as well as within the HMA-treated subgroup (p = 0.0071). These data confirm the value of testing co-occurring somatic alterations even within a high-grade TP53-mutated myeloid neoplasm cohort.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646097","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

Real-world experience of paediatric acute promyelocytic leukaemia in the United Kingdom and Ireland. 英国和爱尔兰儿科急性早幼粒细胞白血病的实际经验。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-17 DOI: 10.1111/bjh.19843

Aditi Vedi, Sarah Maria Leiter, Irum Latif Memon, Arunthethy Mahendrayogam, Elsje Van Rijswijk, Urmila Uparkar, Geoff Shenton, Amelie Trinquand, Katherine Clesham, Vanessa McLelland, Helen Campbell, Katharine Patrick, Lyndsey Thompson, Susan Baird, Philip Connor, Donna Lancaster, Beki James

引用次数: 0

Greater preservation of SARS-CoV-2 neutralising antibody responses following the ChAdOx1-S (AZD1222) vaccine compared with mRNA vaccines in haematopoietic cell transplant recipients. 与 mRNA 疫苗相比，造血细胞移植受者接种 ChAdOx1-S (AZD1222) 疫苗后，SARS-CoV-2 中和抗体反应的保存率更高。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-17 DOI: 10.1111/bjh.19874

Hayley Colton, Natalie Barratt, Nigel Temperton, Hailey Hornsby, Adrienn Angyal, Irina Grouneva, Benjamin B Lindsey, Pamela Kearns, Eleanor Barnes, Carl S Goodyear, Alex Richter, David Thomas, Gordon Cook, Iain B McInnes, Michelle Willicombe, Stefan Siebert, Kim Orchard, Rachael Selby, Sarah Bowden, Paul J Collini, Ann Pope, Amanda Kirkham, Barbara Kronsteiner, Susanna J Dunachie, Paul Miller, Jennifer Clay, Erin Hurst, Ram Malladi, Murali Kesavan, Francesca Kinsella, Robin Sanderson, Kwee L Yong, Daniel Rea, Helen Parry, Sean H Lim, John A Snowden, Thushan I de Silva

{"title":"Greater preservation of SARS-CoV-2 neutralising antibody responses following the ChAdOx1-S (AZD1222) vaccine compared with mRNA vaccines in haematopoietic cell transplant recipients.","authors":"Hayley Colton, Natalie Barratt, Nigel Temperton, Hailey Hornsby, Adrienn Angyal, Irina Grouneva, Benjamin B Lindsey, Pamela Kearns, Eleanor Barnes, Carl S Goodyear, Alex Richter, David Thomas, Gordon Cook, Iain B McInnes, Michelle Willicombe, Stefan Siebert, Kim Orchard, Rachael Selby, Sarah Bowden, Paul J Collini, Ann Pope, Amanda Kirkham, Barbara Kronsteiner, Susanna J Dunachie, Paul Miller, Jennifer Clay, Erin Hurst, Ram Malladi, Murali Kesavan, Francesca Kinsella, Robin Sanderson, Kwee L Yong, Daniel Rea, Helen Parry, Sean H Lim, John A Snowden, Thushan I de Silva","doi":"10.1111/bjh.19874","DOIUrl":"https://doi.org/10.1111/bjh.19874","url":null,"abstract":"Whilst SARS-CoV-2 mRNA vaccines generate high neutralising antibodies (nAb) in most individuals, haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) recipients respond poorly. HSCT/CAR-T treatment ablates existing immune memory, with recipients requiring revaccination analogous to being vaccine naive. An optimal revaccination strategy for this cohort has not been defined. Factors predicting immunogenicity following three ancestral SARS-CoV-2 vaccines were assessed in 198 HSCT/CAR-T recipients and 96 healthcare workers (HCWs) recruited to multicentre studies. Only 25% of HSCT/CAR-T recipients generated nAbs following one dose, with titres 167-fold and 7-fold lower than that in HCWs after the first and second doses, respectively. Lower post-second dose nAb titres were associated with older age, rituximab use, and previous HSCT. ChAdOx1-S recipients were more likely to generate nAbs compared with mRNA vaccines, with titres comparable to HCWs. In contrast, nAbs were significantly lower in HSCT/CAR-T recipients than HCWs after mRNA vaccination. The poor first-dose immunogenicity in HSCT/CAR-T recipients suggests a minimum licensed dosing interval could limit the period of vulnerability following HSCT/CAR-T. The relative preservation of nAbs with ChAdOx1-S vaccination highlights the importance of evaluating alternative platforms to mRNA vaccination within this highly vulnerable clinical cohort.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646077","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

Impact of hydroxycarbamide treatment on the whole-blood transcriptome in sickle cell disease. 羟基甲酰胺治疗对镰状细胞病全血转录组的影响。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-17 DOI: 10.1111/bjh.19839

Varsha Bhat, Alka A Potdar, G Karen Yu, Greg Gibson, Vivien A Sheehan

{"title":"Impact of hydroxycarbamide treatment on the whole-blood transcriptome in sickle cell disease.","authors":"Varsha Bhat, Alka A Potdar, G Karen Yu, Greg Gibson, Vivien A Sheehan","doi":"10.1111/bjh.19839","DOIUrl":"https://doi.org/10.1111/bjh.19839","url":null,"abstract":"Hydroxycarbamide (HC) is the most widely used therapeutic for individuals with sickle cell disease (SCD, including sickle cell anemia and other forms of the disease). HC's clinical benefits are primarily associated with its ability to induce foetal haemoglobin (HbF); this limited view of HC's therapeutic potential may lead to its discontinuation when a modest amount of HbF is induced. A better understanding of the HbF-independent effects of HC on genes and pathways relevant to SCD pathophysiology is therefore needed. In this study, we performed bulk RNA-Seq on whole blood samples collected from a cohort of 25 paediatric patients with SCD to identify genes and pathways that are affected by treatment with HC. At the maximum tolerated dose (MTD) of HC, patients showed altered expression levels of several genes and biological pathways. Pathways related to haeme metabolism, interferon-alpha response, and interferon-gamma response were significantly downregulated at HC MTD relative to the matched pre-HC samples. Pathways linked with IL2-STAT5 signalling and TNFα signalling via NF-Kβ were observed to be up-regulated at HC MTD. These results illustrate the range of effects exerted by HC during therapy for SCD and pave the way for an improved understanding of the HbF induction-independent benefits of HC.","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646080","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

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-14 DOI: 10.1111/bjh.19887

Giuseppe Bertuglia, Sara Bringhen, Benedetto Bruno, Giorgia Andrea Impalà, Mattia D'Agostino

引用次数: 0

Dutcher bodies and Russell bodies in a case of t(11;14) multiple myeloma. 一例 t（11;14）多发性骨髓瘤患者的 Dutcher 体和 Russell 体。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-14 DOI: 10.1111/bjh.19890

Jing Wu, Wei Cai, Mi Jiang

引用次数: 0

Dissecting the genomic traits and clinical course of secondary myelodysplastic syndrome following aplastic anaemia: A milestone. 剖析再生障碍性贫血后继发性骨髓增生异常综合征的基因组特征和临床过程：一个里程碑。

IF 5.1 2区医学

British Journal of Haematology Pub Date : 2024-11-14 DOI: 10.1111/bjh.19898

Carmelo Gurnari, Valeria Visconte

引用次数: 0