Haematologica最新文献

{"title":"Acute myeloid leukemia drug tolerant persister cells survive chemotherapy by transiently increasing plasma membrane rigidity, that also increases their sensitivity to immune cell killing.","authors":"Yael Morgenstern, JongBok Lee, Yoosu Na, Brandon Y Lieng, Nicholas S Ly, William D Gwynne, Rose Hurren, Li Ma, Dakai Ling, Marcela Gronda, Andrea Arruda, Avraham Frisch, Tsila Zuckerman, Yishai Ofran, Mark D Minden, Li Zhang, Catherine O'Brien, Andrew T Quaile, J Rafael Montenegro-Burke, Aaron D Schimmer","doi":"10.3324/haematol.2024.286018","DOIUrl":"https://doi.org/10.3324/haematol.2024.286018","url":null,"abstract":"<p><p>Resistance to chemotherapy remains a major hurdle to the cure of Acute Myeloid Leukemia (AML) patients. Recent studies indicate a minority of malignant cells, termed drug-tolerant persisters (DTPs), stochastically upregulate stress pathways to evade cell death upon acute exposure to chemotherapy without acquiring new genetic mutations. This chemoresistant state is transient and the cells return to baseline after removal of chemotherapy. Yet, the mechanisms employed by DTPs to resist chemotherapy are not well understood and it is largely unknown whether these mechanisms are also seen in patients receiving chemotherapy. Here, we used leukemia cell lines, primary AML patient samples and samples from patients with AML receiving systemic chemotherapy to study the DTP state. We demonstrated that a subset of AML cells transiently increases membrane rigidity to resist killing due to acute exposure to Daunorubicin and Ara-C. Upon removal of the chemotherapy, membrane rigidity returned to baseline and the cells regained chemosensitivity. Although resistant to chemotherapy, the increased membrane rigidity, rendered AML cells more susceptible to T-cell mediated killing. Thus, we identified a novel mechanism by which DTP leukemic cells evade chemotherapy and a strategy to eradicate these persistent cells.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681550","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}

{"title":"Teclistamab in relapsed refractory multiple myeloma: a multi-institutional real-world study from the French early access program.","authors":"Aurore Perrot, Cyrille Hulin, Ariane Boumendil, Hamza Manjra, Antoine Leveque, Carolyne Croizier, Arthur Dony, Mohamad Mohty, Murielle Roussel, Salomon Manier, Frédérique Orsini-Piocelle, Loic Bauschert, Arthur Bobin, Laurent Frenzel, Laure Vincent, Claire Breal, Jean Richard Eveillard, Thomas Gerome, Mourad Tiab, Emilie Chalayer, Rakiba Belkhir, Clara Mariette, Perrine Moyer, Thomas Chalopin, Brieuc Cherel, Lydia Montes, Arthur Coste, Reza Tabrizi, Lionel Karlin, Daniella Robu, Amandine Huguet, Stéphanie Harel, Philippe Moreau","doi":"10.3324/haematol.2024.286118","DOIUrl":"https://doi.org/10.3324/haematol.2024.286118","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681702","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}

{"title":"Is age just a number? Intensive therapy for core binding factor acute myeloid leukemia in older adults.","authors":"Benson M George, Marlise R Luskin","doi":"10.3324/haematol.2024.286640","DOIUrl":"https://doi.org/10.3324/haematol.2024.286640","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619074","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}

{"title":"\"The End of the Golden Weather\": therapeutic strategies for mantle cell lymphoma relapsed or refractory to covalent BTK inhibitors.","authors":"Brian T Grainger, Chan Y Cheah","doi":"10.3324/haematol.2024.286205","DOIUrl":"https://doi.org/10.3324/haematol.2024.286205","url":null,"abstract":"<p><p>Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma which is often characterised by a pattern of continued relapse after frontline chemoimmunotherapy. Although patients are usually able to regain durable disease control with covalent Bruton's tyrosine kinase inhibitors (cBTKi) at first relapse, it is now appreciated that such responses are often not sustained and the management of such patients represents a significant area of unmet need. There is an imperative to better understand resistance mechanisms and identify high-risk subsets of patients for whom cBTKi responses may be particularly short. Allogeneic stem cell transplant has an established role in appropriate candidates, however contemporary consensus is to preferentially offer chimeric antigen receptor (CAR) T-cell therapy. In this Review, we consider the available data on both existing and emerging treatment options, including non-covalent BTK inhibitors, bispecific antibodies, antibody-drug conjugates and Bcl-2 inhibitors and propose a treatment strategy prioritising clinical trials where available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619064","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}

{"title":"Challenges associated with access to recently developed hemophilia treatments in routine care: perspectives of healthcare professionals.","authors":"Karin Berger, Roxy H O'Rourke, Matteo Nicola Dario Di Minno, Angelika Batorova, Kaan Kavakli, Pier Mannuccio Mannucci, Wolfgang Schramm, Rhonda L Bohn, Louis Aledort","doi":"10.3324/haematol.2024.285647","DOIUrl":"https://doi.org/10.3324/haematol.2024.285647","url":null,"abstract":"<p><p>The treatment landscape for haemophilia continues to rapidly develop, and expectations for future treatment success are high. There is limited information on the challenges to accessing new and innovative therapies. The aim of this study was to explore challenges with accessing haemophilia treatment from the perspective of healthcare professionals (HCPs). A crosssectional study design was used. A pilot-tested, online survey was distributed to haemophilia treatment centres in Australia, Canada, France, Italy, New Zealand, Republic of Ireland, Turkey, the United States, and the United Kingdom. The questionnaire covered questions on product access, economic considerations, health technology assessment requirements, and patient organization involvement. The results were analyzed descriptively using SPSS. A total of 154 HCPs completed the questionnaire. There was heterogeneity across countries, regions, and centres regarding HCPs' knowledge of access to novel recently developed treatments. Notable limitations to access were reported such as differences in access based on age of patient and type of product, economic considerations, and the growing influence of HTA bodies. Many countries have a hemophilia patient organization that does not have a vote at the decision-making table. There is a need to empower HCPs to better understand national healthcare structures and decisions that lead to access limitations. Requirements from HTA bodies must be understood to optimally design clinical studies and value generation of treatment options. This may strengthen the haemophilia treatment centre's voice to collectively mandate for exchange with key involved individuals, such as the payers and politicians for the provision of optimal therapy.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619066","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}

{"title":"Germline genetics, disease, and exposure to medication influence longitudinal dynamics of clonal hematopoiesis.","authors":"Taralynn Mack, Yash Pershad, Caitlyn Vlasschaert, Cosmin A Bejan, Jonathan Brett Heimlich, Yajing Li, Nicole A Mickels, Joseph C Van Amburg, Jessica Ulloa, Alexander J Silver, Leo Y Luo, Angela Jones, Paul Brent Ferrell, Ashwin Kishtagari, Yaomin Xu, Michael R Savona, Alexander G Bick","doi":"10.3324/haematol.2024.286513","DOIUrl":"https://doi.org/10.3324/haematol.2024.286513","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619068","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}

{"title":"Loncastuximab in high-risk and heavily pretreated relapsed / refractory diffuse large B-cell lymphoma: a real-world analysis from 21 US centers.","authors":"Viktoriya Zelikson, Ashwath Gurumurthi, Yazeed Sawalha, Kaitlin Annunzio, Aditi Saha, Ning Dong, David Qualls, Behzad Amoozgar, Brad Kahl, John Baird, Pavan Challa, Scott F Huntington, Jennifer Santos, Steven Bair, Mayur Narkhede, Shuning Li, Zachary Frosch, Carrie Ho, Stephen D Smith, Allison Winter, Daniel Landsburg, Fateeha Furqan, Mehdi Hamadani, Katelin Baird, Jason Romancik, Hanan Alharthy, Jennie Law, Leyla Bojanini, Ranjana Advani, Boyu Hu, Patrick Connor Johnson, Natalie S Grover, Mwanasha Merril, Jennifer L Crombie, Nazila Shafagati, Cole Sterling, Loretta J Nastoupil, Narendranath Epperla, Emily C Ayers","doi":"10.3324/haematol.2024.285977","DOIUrl":"https://doi.org/10.3324/haematol.2024.285977","url":null,"abstract":"<p><p>Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab-teserine (Lonca) is an antibody drug conjugate (ADC) which was FDA approved for R/R DLBCL patients who have received at least 2 prior lines of therapy based on the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting (RWS). This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis includes 187 patients with notably higher risk baseline features compared to LOTIS-2 including a higher proportion of patients with bulky disease (17% vs 0%), high-grade B-cell histology (HGBL) (22% vs 8%), and increased number of prior lines of therapy (median 4 vs 3). The complete response (CR) rate was 14% and overall response rate (ORR) was 32%. Median event free (EFS) and overall survival (OS) were 2.1 and 4.6 months, respectively. Those with bulky disease and HGBL had significantly worse outcomes, and those with non-germinal center cell of origin and CR to most recent line of therapy demonstrated superior outcomes. In summary, in this largest retrospective cohort study of Lonca in the RWS, the response rates, EFS, and OS were lower than those reported in LOTIS-2, which is likely reflective of its use in higher risk and more heavily pre-treated patients within the real world compared to those enrolled on clinical study.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":"0"},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619079","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}

{"title":"The different faces of thrombotic thrombocytopenic purpura.","authors":"Paul Knöbl","doi":"10.3324/haematol.2024.286504","DOIUrl":"https://doi.org/10.3324/haematol.2024.286504","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619100","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}

{"title":"Succinyl-coenzyme A: a key metabolite and succinyl group donor in erythropoiesis.","authors":"Kevin Rouault-Pierre","doi":"10.3324/haematol.2024.286672","DOIUrl":"https://doi.org/10.3324/haematol.2024.286672","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619097","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}

{"title":"Short-course subcutaneous alemtuzumab induces clinical responses in relapsed T-cell large granular leukemia.","authors":"Miguel Ruiz, Zachary Braunstein, Eric McLaughlin, Anjali Mishra, Pierluigi Porcu, Jonathan E Brammer","doi":"10.3324/haematol.2024.286235","DOIUrl":"https://doi.org/10.3324/haematol.2024.286235","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619082","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}