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Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation. 儿童造血细胞移植长期存活患者克隆造血能力增加。
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-13 DOI: 10.1158/2643-3230.BCD-24-0136
Konradin F Müskens, Nienke Wieringa, Maaike G J M van Bergen, Joëll E Bense, Brigit M Te Pas, Anne P J de Pagter, Arjan C Lankester, Marc B Bierings, Donna S Neuberg, Saskia Haitjema, Leontien C M Kremer, Gerwin A Huls, Stefan Nierkens, Joop H Jansen, Caroline A Lindemans, Aniek O de Graaf, Mirjam E Belderbos
{"title":"Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation.","authors":"Konradin F Müskens, Nienke Wieringa, Maaike G J M van Bergen, Joëll E Bense, Brigit M Te Pas, Anne P J de Pagter, Arjan C Lankester, Marc B Bierings, Donna S Neuberg, Saskia Haitjema, Leontien C M Kremer, Gerwin A Huls, Stefan Nierkens, Joop H Jansen, Caroline A Lindemans, Aniek O de Graaf, Mirjam E Belderbos","doi":"10.1158/2643-3230.BCD-24-0136","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-24-0136","url":null,"abstract":"<p><p>In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.01-0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (odds ratio: 1.07, p<0.001) and the HCT procedure (odds ratio: 2.53, p=0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (VAF >0.10) were found exclusively in HCT recipients. Notably, CH was also detected within 15 years after a cord blood HCT. Inflammatory processes around graft infusion were associated with CH presence. Future studies are required to track the evolution of post-transplant CH and its impact on future cardiovascular disease, second malignancies and overall survival.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Venetoclax-Based Combination Regimens in Acute Myeloid Leukemia. 基于 Venetoclax 的急性髓性白血病联合疗法
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-08 DOI: 10.1158/2643-3230.BCD-24-0171
Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D DiNardo, Caitlin R Rausch, Farhad Ravandi, Tapan M Kadia
{"title":"Venetoclax-Based Combination Regimens in Acute Myeloid Leukemia.","authors":"Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D DiNardo, Caitlin R Rausch, Farhad Ravandi, Tapan M Kadia","doi":"10.1158/2643-3230.BCD-24-0171","DOIUrl":"10.1158/2643-3230.BCD-24-0171","url":null,"abstract":"<p><strong>Significance: </strong>In recent years, there has been tremendous interest surrounding the integration of venetoclax into both non-intensive and intensive chemotherapy regimens for AML. However, with this increasing utilization of venetoclax, considerable questions surrounding key issues such as dosing strategies and the practicality of venetoclax administration have arisen. This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this agent.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"23-37"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Total (Immuno)Therapy: Version 2.0. 全面（免疫）疗法》：2.0 版。
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-08 DOI: 10.1158/2643-3230.BCD-24-0236
Susan Bal, Luciano J Costa
{"title":"Total (Immuno)Therapy: Version 2.0.","authors":"Susan Bal, Luciano J Costa","doi":"10.1158/2643-3230.BCD-24-0236","DOIUrl":"10.1158/2643-3230.BCD-24-0236","url":null,"abstract":"<p><p>Among patients with poly-refractory myeloma, autologous chimeric antigen receptor T-cell therapy offers exceptional promise. With the availability of bispecific antibodies, a total immunotherapeutic strategy in combination with chimeric antigen receptor T-cell therapy is now feasible. See related article by Fandrei et al., p. 38.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"10-12"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap. 最小残留病作为加速骨髓瘤药物审批的早期终点：路线图
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-08 DOI: 10.1158/2643-3230.BCD-24-0292
Ola Landgren, Sean M Devlin
{"title":"Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap.","authors":"Ola Landgren, Sean M Devlin","doi":"10.1158/2643-3230.BCD-24-0292","DOIUrl":"10.1158/2643-3230.BCD-24-0292","url":null,"abstract":"<p><strong>Significance: </strong>The acceptance of MRD-negative complete response as an endpoint that is reasonably likely to predict clinical benefit will allow for the design of streamlined clinical trials for accelerated approval, enabling significantly faster patient access to novel therapies. Cooperative efforts were required to obtain and analyze clinical trial data from multiple sponsors and to determine the best approach to analysis with a relatively limited number of available datasets. The process to evaluate MRD as an intermediate endpoint, undertaken jointly by myeloma researchers and industry, with feedback from the FDA, serves as a roadmap for other areas of oncology to develop intermediate endpoints.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"13-22"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells. CD33-CD123 IF-THEN门控降低毒性，同时增强aml靶向CAR-T细胞的特异性和记忆表型。
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-08 DOI: 10.1158/2643-3230.BCD-23-0258
Samy Jambon, Jianping Sun, Shawn Barman, Sakunthala Muthugounder, Xue Rachel Bito, Armita Shadfar, Alexandra E Kovach, Brent L Wood, Varsha Thoppey Manoharan, A Sorana Morrissy, Deepa Bhojwani, Alan S Wayne, Michael A Pulsipher, Yong-Mi Kim, Shahab Asgharzadeh, Chintan Parekh, Babak Moghimi
{"title":"CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells.","authors":"Samy Jambon, Jianping Sun, Shawn Barman, Sakunthala Muthugounder, Xue Rachel Bito, Armita Shadfar, Alexandra E Kovach, Brent L Wood, Varsha Thoppey Manoharan, A Sorana Morrissy, Deepa Bhojwani, Alan S Wayne, Michael A Pulsipher, Yong-Mi Kim, Shahab Asgharzadeh, Chintan Parekh, Babak Moghimi","doi":"10.1158/2643-3230.BCD-23-0258","DOIUrl":"10.1158/2643-3230.BCD-23-0258","url":null,"abstract":"<p><strong>Significance: </strong>Our study demonstrates the use of \"IF-THEN\" SynNotch-gated CAR-T cells targeting CD33 and CD123 in AML reduces off-tumor toxicity. This strategy enhances T-cell phenotype, improves expansion, preserves HSPCs, and mitigates cytokine release syndrome-addressing critical limitations of existing AML CAR-T therapies.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"55-72"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma. 双特异性抗体是治疗复发/难治性多发性骨髓瘤的 BCMA CAR-T 细胞疗法的桥梁。
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-08 DOI: 10.1158/2643-3230.BCD-24-0118
David Fandrei, Sabine Seiffert, Michael Rade, Susanne Rieprecht, Nico Gagelmann, Patrick Born, Thomas Wiemers, Heike Weidner, Markus Kreuz, Tamara Schassberger, Jannik Koßmann, Marlene Mangold, Daniel Fürst, Luise Fischer, Ronny Baber, Simone Heyn, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Klaus H Metzeler, Marco Herling, Madlen Jentzsch, Georg-Nikolaus Franke, Ulrike Köhl, Maik Friedrich, Andreas Boldt, Kristin Reiche, Uwe Platzbecker, Vladan Vucinic, Maximilian Merz
{"title":"Bispecific Antibodies as Bridging to BCMA CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma.","authors":"David Fandrei, Sabine Seiffert, Michael Rade, Susanne Rieprecht, Nico Gagelmann, Patrick Born, Thomas Wiemers, Heike Weidner, Markus Kreuz, Tamara Schassberger, Jannik Koßmann, Marlene Mangold, Daniel Fürst, Luise Fischer, Ronny Baber, Simone Heyn, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Klaus H Metzeler, Marco Herling, Madlen Jentzsch, Georg-Nikolaus Franke, Ulrike Köhl, Maik Friedrich, Andreas Boldt, Kristin Reiche, Uwe Platzbecker, Vladan Vucinic, Maximilian Merz","doi":"10.1158/2643-3230.BCD-24-0118","DOIUrl":"10.1158/2643-3230.BCD-24-0118","url":null,"abstract":"<p><p>Establishing a strategy for sequencing of T cell-redirecting therapies for relapsed/refractory multiple myeloma (RRMM) is a pressing clinical need. We longitudinally tracked the clinical and immunologic impact of bispecific T cell-engaging antibodies (BsAb) as bridging therapy (BT) to subsequent B-cell maturation antigen-directed chimeric antigen receptor T (CAR-T) cell therapies in 52 patients with RRMM. BsAbs were a potent and safe option for BT, achieving the highest overall response rate (100%) to BT compared with chemotherapy, anti-CD38, or anti-SLAMF7 antibody-based regimens (46%). We observed early CD4+CAR+ and delayed CD8+CAR+ T-cell expansion in patients receiving BsAbs as BT. In vitro cytotoxicity of CAR-T cells was comparable among BT options. Single-cell analyses revealed increased clonality in the CD4+ and CD8+ T-cell compartments in patients with previous exposure to BsAbs at leukapheresis and on day 30 after CAR-T cell infusion. This study demonstrates the feasibility and efficacy of BT with BsAbs for CAR-T cell therapy in RRMM. Significance: CAR-T cell therapy and BsAbs have revolutionized treatment of triple-class refractory multiple myeloma; however, optimal sequencing is unknown. We demonstrate that BT with BsAb before B-cell maturation antigen-directed CAR-T cell therapy is safe and effective, which might have implications for other hematologic malignancies as well. See related commentary by Bal and Costa, p. 10.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"38-54"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New Approvals Advancing Blood Cancer Medicine. 新批准推动血癌医学发展。
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-08 DOI: 10.1158/2643-3230.BCD-24-0300
{"title":"New Approvals Advancing Blood Cancer Medicine.","authors":"","doi":"10.1158/2643-3230.BCD-24-0300","DOIUrl":"10.1158/2643-3230.BCD-24-0300","url":null,"abstract":"<p><p>Recent advancements in clinical tools for blood cancers are highlighted in this article, adapted from the 14th edition of the annual AACR Cancer Progress Report (https://cancerprogressreport.aacr.org/progress/) to the US Congress and the public.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"5-9"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acknowledgment to Reviewers. 感谢审稿人。
IF 11.5
Blood Cancer Discovery Pub Date : 2025-01-08 DOI: 10.1158/2643-3230.BCD-6-1-AR
{"title":"Acknowledgment to Reviewers.","authors":"","doi":"10.1158/2643-3230.BCD-6-1-AR","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-6-1-AR","url":null,"abstract":"","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":"6 1","pages":"73-74"},"PeriodicalIF":11.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamics of Immune Reconstitution and Impact on Outcomes Across CAR-T Cell Products in Large B-Cell Lymphoma. 大 B 细胞淋巴瘤 CAR-T 细胞产品的免疫重建动态及其对疗效的影响
IF 11.5
Blood Cancer Discovery Pub Date : 2024-12-12 DOI: 10.1158/2643-3230.BCD-24-0163
Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval
{"title":"Dynamics of Immune Reconstitution and Impact on Outcomes Across CAR-T Cell Products in Large B-Cell Lymphoma.","authors":"Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval","doi":"10.1158/2643-3230.BCD-24-0163","DOIUrl":"https://doi.org/10.1158/2643-3230.BCD-24-0163","url":null,"abstract":"<p><p>Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immune suppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. Here, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.9%, lisocabtagene maraleucel 30.4%, tisagenlecleucel 24.7%). Following infusion, patients remain persistently immunosuppressed, with 48.1% having CD4+ T cell counts <200/µL and median CD3-19+ B cell counts remaining zero through 1 year after CAR-T. IR differences exist by product, with fastest CD4+ T cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7-45RA- effector memory subset. Natural killer cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR: 0.647; 95% CI: 0.476-0.880) and overall survival (HR: 0.637; 95% CI: 0.441-0.920) and inversely correlated with inflammatory markers measured at time of infusion.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The crossroads of clonal evolution, differentiation hierarchy and ontogeny in leukemia development. 白血病发生中克隆进化、分化层次和个体发生的十字路口。
IF 11.5
Blood Cancer Discovery Pub Date : 2024-12-09 DOI: 10.1158/2643-3230.BCD-24-0235
Christopher M Sturgeon, Elvin Wagenblast, Franco Izzo, Eirini P Papapetrou
{"title":"The crossroads of clonal evolution, differentiation hierarchy and ontogeny in leukemia development.","authors":"Christopher M Sturgeon, Elvin Wagenblast, Franco Izzo, Eirini P Papapetrou","doi":"10.1158/2643-3230.BCD-24-0235","DOIUrl":"10.1158/2643-3230.BCD-24-0235","url":null,"abstract":"<p><p>Transformative technologies to sequence tumor genomes at large scale and single-cell resolution have exposed the repertoire of genetic alterations that are present in leukemia genomes, the timing of their acquisition and patterns of their co-occurrence. In parallel, single-cell multi-omics technologies are allowing us to map the differentiation paths and hierarchical structures of malignant cells and giving us a glimpse into hematopoietic development in prenatal life. We propose that interrogating how the genetic evolution, differentiation hierarchy and ontogeny of malignant myeloid cells intersect with each other, using new experimental systems and multimodal technologies, will fuel the next generation of research breakthroughs.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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