Seminars in hematology最新文献_第6页

outside front cover, PMS 8883 metallic AND 4/C 封面外侧，PMS 8883 金属色和 4/C

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/S0037-1963(24)00114-8

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Accelerating accessibility of CAR-T/NK therapies – Are AlloCARs and rapid manufacturing platforms the road ahead in improving access in multiple myeloma? 加快 CAR-T/NK 疗法的普及--AlloCARs 和快速制造平台是改善多发性骨髓瘤治疗普及的必由之路吗？

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.09.001

Sridevi Rajeeve , Abhinav Hoskote , Sham Mailankody

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Tuning CAR T-cell therapies for efficacy and reduced toxicity 调整 CAR T 细胞疗法，提高疗效并降低毒性

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.07.003

Danielle Blud , Patricia Rubio-Reyes , Rachel Perret , Robert Weinkove

{"title":"Tuning CAR T-cell therapies for efficacy and reduced toxicity","authors":"Danielle Blud , Patricia Rubio-Reyes , Rachel Perret , Robert Weinkove","doi":"10.1053/j.seminhematol.2024.07.003","DOIUrl":"10.1053/j.seminhematol.2024.07.003","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T-cell therapies are a standard of care for certain relapsed or refractory B-cell cancers. However, many patients do not respond to CAR T-cell therapy or relapse later, short- and long-term toxicities are common, and current CAR T-cell therapies have limited efficacy for solid cancers. The gene engineering inherent in CAR T-cell manufacture offers an unprecedented opportunity to control cellular characteristics and design products that may overcome these limitations. This review summarises available methods to “tune” CAR T-cells for optimal efficacy and safety. The components of a typical CAR, and the modifications that can influence CAR T-cell function are discussed. Methods of engineering passive, inducible or autonomous control mechanisms into CAR T-cells, allowing selective limitation or enhancement of CAR T-cell activity are reviewed. The impact of manufacturing processes on CAR T-cell function are considered, including methods of limiting CAR T-cell terminal differentiation and exhaustion, and the use of specific T-cell subsets as the CAR T starting material. We discuss the use of multicistronic transgenes and multiplexed gene editing. Finally, we highlight the need for innovative clinical trial designs if we are to make the most of the opportunities offered by CAR T-cell therapies.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 333-344"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141713143","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}

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License for a CAR T: Examining patient eligibility CAR T 许可：审查患者资格

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.07.001

Neha Akkad , Dai Chihara

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Mobilizing CARs: Benefits, drawbacks, and directions for outpatient CAR T-cell therapy 调动 CAR：门诊 CAR T 细胞疗法的优点、缺点和发展方向。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.08.003

Jennifer S. Woo , Kim Nguyen , Lawrence Liu , Amrita Krishnan , Tanya Siddiqi , Azra Borogovac

{"title":"Mobilizing CARs: Benefits, drawbacks, and directions for outpatient CAR T-cell therapy","authors":"Jennifer S. Woo , Kim Nguyen , Lawrence Liu , Amrita Krishnan , Tanya Siddiqi , Azra Borogovac","doi":"10.1053/j.seminhematol.2024.08.003","DOIUrl":"10.1053/j.seminhematol.2024.08.003","url":null,"abstract":"<div><div>Chimeric antigen receptor T-cell (CAR-T) therapy has heralded a new era in the treatment of various hematological malignancies, increasingly being utilized in earlier lines of therapy. Moreover, cellular therapies are currently under investigation for their potential in treating solid malignancies and autoimmune disorders. As the scope of indications for CAR-T therapy continues to expand, along with the associated reductions in costs and hospital admissions, many medical centers are transitioning towards outpatient CAR-T models. Moreover, ongoing efforts to mitigate complications such as cytokine release syndrome (CRS) or neurotoxicity include the development of premedication strategies, prompt management of adverse events, and the advancement of newer, safer CAR-T cell therapies. However, despite these advancements, the inherent risk of these life-threatening complications remains a critical concern in CAR-T therapy. Institutions must diligently anticipate and effectively manage these complications to ensure the safety and well-being of patients undergoing CAR-T therapy. This includes establishing robust protocols for timely identification and intervention of adverse events, and seamless pathways for transitioning patients to a higher level of care if necessary. This review provides an overview of the current landscape of outpatient CAR-T therapy and offers essential insights into the key clinical and operational considerations needed to implement a successful outpatient CAR-T program.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 273-283"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353083","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}

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Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma 速度与激情：利用嵌合抗原受体 T 细胞治疗多发性骨髓瘤，在治愈之路上换挡加速

IF 5 3区医学

Seminars in hematology Pub Date : 2024-10-01 DOI: 10.1053/j.seminhematol.2024.07.002

Nico Gagelmann , Maximilian Merz

{"title":"Fast and furious: Changing gears on the road to cure with chimeric antigen receptor T cells in multiple myeloma","authors":"Nico Gagelmann , Maximilian Merz","doi":"10.1053/j.seminhematol.2024.07.002","DOIUrl":"10.1053/j.seminhematol.2024.07.002","url":null,"abstract":"<div><div>Based on the pivotal KarMMa-1 and CARTITUDE-1 studies, Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel) have been approved to treat multiple myeloma patients, who have been exposed to at least 1 proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody after 4 or 3 lines of therapy, respectively. The unprecedented rates of deep and long-lasting remissions have been meanwhile confirmed in multiple real-world analyses and more recently, the KarMMa-3 and CARTITUDE-4 studies lead to the approval in earlier lines of therapy. It is currently believed that ultimately all patients with relapsed/refractory multiple myeloma experience relapse after anti-BCMA CAR T-cell therapies. There is a plethora of CAR T-cell therapies targeting novel antigens, with the aim to overcome current CAR T-cell resistance. In this review, we will summarize current evidence of novel antigens and their clinical potential. Together with current CAR T-cell therapy and T-cell engagers, these approaches might lead us to the next frontier in multiple myeloma: total immunotherapy and the road to chemotherapy-free cure.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 5","pages":"Pages 306-313"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696986","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

The pediatric approach to Hodgkin lymphoma 霍奇金淋巴瘤的儿科治疗方法

IF 5 3区医学

Seminars in hematology Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.05.003

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Molecular biomarkers in classic Hodgkin lymphoma 典型霍奇金淋巴瘤的分子生物标志物。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.05.005

{"title":"Molecular biomarkers in classic Hodgkin lymphoma","authors":"","doi":"10.1053/j.seminhematol.2024.05.005","DOIUrl":"10.1053/j.seminhematol.2024.05.005","url":null,"abstract":"<div><p><span><span>Classic Hodgkin lymphoma<span> is a unique B-cell derived malignancy<span> featuring rare malignant Hodgkin and Reed Sternberg (HRS) cells that are embedded in a quantitively dominant tumor microenvironment (TME). Treatment of classic Hodgkin lymphoma has significantly evolved in the past decade with improving treatment outcomes for newly diagnosed patients and the minority of patients suffering from </span></span></span>disease progression<span><span>. However, the burden of toxicity and treatment-related long-term sequelae remains high in a typically young patient population. This highlights the need for better molecular biomarkers aiding in risk-adapted treatment strategies and predicting response to an increasing number of available treatments that now prominently involve multiple </span>immunotherapy<span> options. Here, we review modern molecular biomarker approaches that reflect both the biology of the malignant HRS cells and cellular components in the TME, while holding the promise to improve diagnostic frameworks for clinical decision-making and be feasible in clinical trials and routine practice. In particular, technical advances in sequencing and analytic pipelines using </span></span></span>liquid biopsies, as well as deep phenotypic characterization of tissue architecture at single-cell resolution, have emerged as the new frontier of biomarker development awaiting further validation and implementation in routine diagnostic procedures.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 221-228"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538549","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}

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The role of autologous stem-cell transplantation in classical Hodgkin lymphoma in the modern era 现代自体干细胞移植在经典霍奇金淋巴瘤中的作用。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.06.003

Gaurav Varma , Catherine Diefenbach

{"title":"The role of autologous stem-cell transplantation in classical Hodgkin lymphoma in the modern era","authors":"Gaurav Varma , Catherine Diefenbach","doi":"10.1053/j.seminhematol.2024.06.003","DOIUrl":"10.1053/j.seminhematol.2024.06.003","url":null,"abstract":"<div><p><span><span><span>Despite excellent cure rates with modern front-line regimens, up to 20% of patients with Hodgkin lymphoma will progress through front-line therapy or experience disease relapse. Worldwide, salvage chemotherapy followed by high-dose chemotherapy with </span>autologous stem cell transplantation<span> (HDT/ASCT) is considered the standard of care for these patients and can cure approximately 50% of relapsed or refractory (R/R) patients in the second line. Brentuximab vedotin (BV), an anti-CD30 </span></span>antibody drug conjugate, and PD1 inhibitors like </span>nivolumab<span> and pembrolizumab<span><span><span>, have high response rates in patients who recur after HDT/ASCT. When used prior to HDT/ASCT, BV and PD1 inhibitors appear to dramatically increase the effectiveness of salvage therapies with complete response rates often double those seen with historic chemotherapy-based regimens and durable </span>progression free survival (PFS) post-HDT/ASCT. Emerging data in adults and from </span>pediatric trials showing a durable PFS in a subset of relapsed patients raises the question of whether HDT/ASCT is essential for cure in R/R patients after PD1 based salvage. Future studies will help clarify if ASCT can omitted PD1 based salvage to avoid the potential toxicity of HDT/ASCT without compromising cure.</span></span></p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 4","pages":"Pages 253-262"},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749003","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

Challenges for HL in the modern era: Questions to move the field forward 现代人类学面临的挑战：推动该领域发展的问题

IF 5 3区医学

Seminars in hematology Pub Date : 2024-08-01 DOI: 10.1053/j.seminhematol.2024.09.002

Catherine Diefenbach MD

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