Vaishali Dulobdas, Amy A. Kirkwood, Fabio Serpenti, Brijesh Gautama, Aikaterini Panopoulou, Amrith Mathew, Sumantha Gabriel, Ram Malladi, Jessica Pealing, Denise Bonney, Emma Nicholson, Caroline Besley, Sara Ghorashian, Andrea Kuhnl, Elizabeth Davies, Jackie Chappell, Anne Black, Tobias Menne, Maeve A. O’Reilly, Robin Sanderson, Sridhar Chaganti
{"title":"Risk factors for CAR T-cell manufacturing failure and patient outcomes in large B-cell lymphoma: a report from the UK National CAR T Panel","authors":"Vaishali Dulobdas, Amy A. Kirkwood, Fabio Serpenti, Brijesh Gautama, Aikaterini Panopoulou, Amrith Mathew, Sumantha Gabriel, Ram Malladi, Jessica Pealing, Denise Bonney, Emma Nicholson, Caroline Besley, Sara Ghorashian, Andrea Kuhnl, Elizabeth Davies, Jackie Chappell, Anne Black, Tobias Menne, Maeve A. O’Reilly, Robin Sanderson, Sridhar Chaganti","doi":"10.1038/s41408-025-01225-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01225-9","url":null,"abstract":"<p>CAR T-cell manufacturing failure (MF) is a situation where the manufacturing process fails to yield a product or results in one which is out-of-specification (OOS). We conducted a multicentre retrospective review of factors contributing to MF and patient outcomes. Of 981 large B-cell lymphoma (LBCL) patients approved for CAR T-cell therapy, 38 (3.87%) had MF. Eleven patients received delayed infusion with a product in-specification (delayed-infused) following 21 remanufacturing attempts. OOS product was infused in 13 (OOS-infused), and 14 were not infused. For comparison, we included 38 LBCL controls without MF; 29 received infusion (controls-infused). Prior bendamustine was the only baseline variable associated with MF risk, largely due to therapy within 6 months; 23.7% MF vs 0% controls (<i>P</i> = 0.0029). Overall survival (OS) and progression-free survival (PFS) were not significantly different for infused patients, with 1-year OS (PFS) of 52.8% (46.2%), 46.8% (24.2%) and 68.4% (41.4%) for OOS-infused, delayed-infused and controls-infused respectively (PFS HR OOS-infused vs controls-infused 1.41, <i>P</i> = 0.40; delayed-infused vs controls-infused 1.64, <i>P</i> = 0.25; and OOS-infused vs delayed-infused 0.86, <i>P</i> = 0.76). CRS, ICANS and cytopenias were not significantly different between cohorts. Outcomes for OOS-infused LBCL patients following MF are encouraging. Remanufacturing led to infusion of a product in-specification in around 50% and may be an option for patients where a suitable OOS product is not available.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"86 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538395","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}
Isolde Summerer, Wencke Walter, Manja Meggendorfer, Torsten Haferlach, Frank Dicker, Stephan Hutter, Niroshan Nadarajah, Anna Stengel, Constanze Kuehn, Wolfgang Kern, John M. Bennett, Claudia Haferlach, Christian Pohlkamp
{"title":"Myeloid neoplasms with MYC-positive double minutes: towards recognition as a distinct entity","authors":"Isolde Summerer, Wencke Walter, Manja Meggendorfer, Torsten Haferlach, Frank Dicker, Stephan Hutter, Niroshan Nadarajah, Anna Stengel, Constanze Kuehn, Wolfgang Kern, John M. Bennett, Claudia Haferlach, Christian Pohlkamp","doi":"10.1038/s41408-025-01244-6","DOIUrl":"https://doi.org/10.1038/s41408-025-01244-6","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"84 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532806","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}
Saubia Fathima, Ali Alsugair, Rong He, Abhishek A. Mangaonkar, Kebede H. Begna, Animesh Pardanani, Cinthya J. Zepeda Mendoza, Kaaren K. Reichard, Naseema Gangat, Ayalew Tefferi
{"title":"Myeloid neoplasms with PHF6 mutations: context-dependent genomic and prognostic characterization in 176 informative cases","authors":"Saubia Fathima, Ali Alsugair, Rong He, Abhishek A. Mangaonkar, Kebede H. Begna, Animesh Pardanani, Cinthya J. Zepeda Mendoza, Kaaren K. Reichard, Naseema Gangat, Ayalew Tefferi","doi":"10.1038/s41408-025-01231-x","DOIUrl":"https://doi.org/10.1038/s41408-025-01231-x","url":null,"abstract":"<p>Recent reports suggest a favorable prognosis for <i>PHF6</i> mutation (<i>PHF6</i><sup>MUT</sup>) in chronic myelomonocytic leukemia (CMML) and unfavorable in acute myeloid leukemia (AML). We accessed 176 consecutive patients with a spectrum of myeloid neoplasms with <i>PHF6</i><sup>MUT</sup>, including AML (<i>N</i> = 67), CMML (<i>N</i> = 49), myelodysplastic syndromes (MDS; <i>N</i> = 36), myeloproliferative neoplasms (MPN; <i>N</i> = 16), and MDS/MPN (<i>N</i> = 8). <i>PHF6</i> mutations were classified as nonsense (43%) or frameshift (30%) with the PHD2 domain being the most frequently (64%) affected region. Median follow-up was 25 months with 110 (63%) deaths and 44 allogenic transplants. Our top-line observations include (a) a distinctly superior overall survival (OS; 81 vs. 18 months; <i>p</i> < 0.01) and blast transformation-free survival (BTFS; “not reached” vs. 44 months; <i>p</i> < 0.01) in patients with CMML vs. those with other myeloid neoplasms, (ii) a higher than expected frequency of isolated loss of Y chromosome, in the setting of CMML (16% vs. expected 6%) and MDS (8% vs expected 2.5%), (iii) a significant association, in MDS, between <i>PHF6</i><sup>MUT</sup> variant allele fraction (VAF) > 20% and inferior OS (HR 3.0, 95% CI 1.1–8.1, multivariate <i>p</i> = 0.02) as well as female gender and inferior BTFS (HR 26.8, 95% CI 1.9–368.3, multivariate <i>p</i> = 0.01), (iv) a relatively favorable median post-transplant survival of 46 months. Multivariable analysis also identified high-risk karyotype (HR 5.1, 95% CI 1.2–20.9, <i>p</i> = 0.02), and hemoglobin <10 g/dL (HR 2.7, 95% CI 1.0–7.2, <i>p</i> = 0.04), as independent predictors of inferior OS in patients with MDS. The current study provides disease-specific information on genotype and prognosis of <i>PHF6</i>-mutated myeloid neoplasms.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"33 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526039","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}
Alexander S. Luchinin, Tigran G. Gevorkyan, Anastasia A. Semenova
{"title":"Multiple myeloma as a challenging multidimensional random process: a data-driven web-based application for treatment selection","authors":"Alexander S. Luchinin, Tigran G. Gevorkyan, Anastasia A. Semenova","doi":"10.1038/s41408-025-01238-4","DOIUrl":"https://doi.org/10.1038/s41408-025-01238-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"130 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517917","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}
Rishi S. Kotecha, Sarah M. Trinder, Anastasia M. Hughes, Benjamin H. Mullin, Sarah Rashid, Jinbo Yuan, Jiake Xu, Owen Duncan, Patrycja Skut, Grace-Alyssa Chua, Sajla Singh, Joyce Oommen, Richard B. Lock, Ursula R. Kees, Sebastien Malinge, Vincent Kuek, Laurence C. Cheung
{"title":"Targeting osteoclasts for treatment of high-risk B-cell acute lymphoblastic leukemia","authors":"Rishi S. Kotecha, Sarah M. Trinder, Anastasia M. Hughes, Benjamin H. Mullin, Sarah Rashid, Jinbo Yuan, Jiake Xu, Owen Duncan, Patrycja Skut, Grace-Alyssa Chua, Sajla Singh, Joyce Oommen, Richard B. Lock, Ursula R. Kees, Sebastien Malinge, Vincent Kuek, Laurence C. Cheung","doi":"10.1038/s41408-025-01239-3","DOIUrl":"https://doi.org/10.1038/s41408-025-01239-3","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"129 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507050","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}
Anish K. Simhal, Ross S. Firestone, Jung Hun Oh, Viswatej Avutu, Larry Norton, Malin Hultcrantz, Saad Z. Usmani, Kylee H. Maclachlan, Joseph O. Deasy
{"title":"High WEE1 expression is independently linked to poor survival in multiple myeloma","authors":"Anish K. Simhal, Ross S. Firestone, Jung Hun Oh, Viswatej Avutu, Larry Norton, Malin Hultcrantz, Saad Z. Usmani, Kylee H. Maclachlan, Joseph O. Deasy","doi":"10.1038/s41408-025-01230-y","DOIUrl":"https://doi.org/10.1038/s41408-025-01230-y","url":null,"abstract":"<p>Current prognostic scores in multiple myeloma (MM) currently rely on disease burden and a limited set of genomic alterations. Some studies have suggested gene expression panels may predict clinical outcomes, but none are presently utilized in clinical practice. The tyrosine kinase <i>WEE1</i> is a critical cell cycle regulator during the S-phase and G2M checkpoint. Abnormal <i>WEE1</i> expression has been implicated in multiple cancers including breast, ovarian, and gastric cancers, but its prognostic signal in MM has not been thoroughly reported. We, therefore, analyzed the MMRF CoMMpass dataset (<i>N</i> = 659) and identified a high-risk group (top tertile) and a low-risk group (bottom tertile) based on <i>WEE1</i> expression sorted in descending order. PFS was significantly different (<i>p</i> < 1e-9) between the groups, which was validated in two independent microarray gene expression profiling (GEP) datasets from the Total Therapy 2 (<i>N</i> = 341) and 3 (<i>N</i> = 214) trials. Our results show that <i>WEE1</i> expression is prognostic independent of known biomarkers, differentiates outcomes associated with known markers, is upregulated independently of its interacting neighbors, and is associated with dysregulated P53 pathways. This suggests that <i>WEE1</i> expression levels may have clinical utility in prognosticating outcomes in newly diagnosed MM and may support the application of <i>WEE1</i> inhibitors to MM preclinical models. Determining the causes of abnormal <i>WEE1</i> expression may uncover novel therapeutic pathways.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"31 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451473","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}
Adam S. Kittai, Ying Huang, Sarah Miller, John N. Allan, Seema A. Bhat, David A. Bond, Danielle M. Brander, John C. Byrd, Julio C. Chavez, Elise Chong, Matthew S. Davids, Alexey V. Danilov, Wei Ding, Mark R. Dowling, Kaitlyn Dvorak-Kornaus, Hannah Freedman, Paul J. Hampel, Carrie Ho, Steven R. Hwang, Prioty Islam, Nikita Malakhov, Matthew Matasar, Cecelia Miller, Zulfa Omer, Sameer A. Parikh, Erin Parry, Kari G. Rabe, Philipp W. Raess, Manoj Rai, Lindsey Roeker, Joanna Rhodes, Kerry A. Rogers, Aditi Saha, Jake Schade, Hamish W. Scott, Mazyar Shadman, Geoffrey Shouse, Alan Skarbnik, Stephen Spurgeon, Deborah M. Stephens, Meghan C. Thompson, Philip A. Thompson, Yucai Wang, Max Yano, Jennifer A. Woyach
{"title":"Outcomes of patients with Richter transformation who received no prior chemoimmunotherapy for their CLL","authors":"Adam S. Kittai, Ying Huang, Sarah Miller, John N. Allan, Seema A. Bhat, David A. Bond, Danielle M. Brander, John C. Byrd, Julio C. Chavez, Elise Chong, Matthew S. Davids, Alexey V. Danilov, Wei Ding, Mark R. Dowling, Kaitlyn Dvorak-Kornaus, Hannah Freedman, Paul J. Hampel, Carrie Ho, Steven R. Hwang, Prioty Islam, Nikita Malakhov, Matthew Matasar, Cecelia Miller, Zulfa Omer, Sameer A. Parikh, Erin Parry, Kari G. Rabe, Philipp W. Raess, Manoj Rai, Lindsey Roeker, Joanna Rhodes, Kerry A. Rogers, Aditi Saha, Jake Schade, Hamish W. Scott, Mazyar Shadman, Geoffrey Shouse, Alan Skarbnik, Stephen Spurgeon, Deborah M. Stephens, Meghan C. Thompson, Philip A. Thompson, Yucai Wang, Max Yano, Jennifer A. Woyach","doi":"10.1038/s41408-025-01236-6","DOIUrl":"https://doi.org/10.1038/s41408-025-01236-6","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451471","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}
Rongtao Xue, Min Dai, Erlie Jiang, Xueying Ou, Fen Huang, Zhiping Fan, Na Xu, Chenhua Yan, Danian Nie, Xinquan Liang, Hong Chen, Jieyu Ye, Ling Jiang, Hui Liu, Hua Jin, Ren Lin, Yu Zhang, Jing Sun, Mingzhe Han, Qifa Liu, Yu Wang, Li Xuan
{"title":"Effect of pre-transplant cytoreductive therapy on the outcomes of patients with MDS or secondary AML evolving from MDS undergoing allo-HSCT: a secondary analysis of an RCT","authors":"Rongtao Xue, Min Dai, Erlie Jiang, Xueying Ou, Fen Huang, Zhiping Fan, Na Xu, Chenhua Yan, Danian Nie, Xinquan Liang, Hong Chen, Jieyu Ye, Ling Jiang, Hui Liu, Hua Jin, Ren Lin, Yu Zhang, Jing Sun, Mingzhe Han, Qifa Liu, Yu Wang, Li Xuan","doi":"10.1038/s41408-025-01233-9","DOIUrl":"https://doi.org/10.1038/s41408-025-01233-9","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"51 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451474","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
