Blood最新文献

{"title":"CAR-DLI for ALL, but not without lymphodepletion.","authors":"Lutz P Müller","doi":"10.1182/blood.2025030291","DOIUrl":"https://doi.org/10.1182/blood.2025030291","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"32 1","pages":"1632-1634"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203946","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":"Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST.","authors":"Maximilian Merz, Nico Gagelmann, Samih Smaili, Sarah Flossdorf, Sandra Sauer, Christof Scheid, Bastian von Tresckow, Gerald Wulf, Katja Weisel, Igor Wolfgang Blau, Monika Engelhardt, Ralph Wäsch, Natalie Schub, Raphael Teipel, Judith Hecker, Johannes Waldschmidt, Britta Besemer, Ben-Niklas Baermann, Simon Call, Leo Hansmann, Francis Ayuketang Ayuk, Marc S Raab, Hermann Einsele, Uwe Platzbecker, Nicolaus Kröger","doi":"10.1182/blood.2025028330","DOIUrl":"10.1182/blood.2025028330","url":null,"abstract":"<p><strong>Abstract: </strong>Cellular therapies targeting B-cell maturation antigen have shown promise in controlled clinical trials, but their impact in broader, diverse patient populations remains underexplored. This study examines the real-world efficacy and safety in 343 triple-class-exposed patients with relapsed and refractory multiple myeloma who received idecabtagene vicleucel (ide-cel; n = 266) or ciltacabtagene autoleucel (cilta-cel; n = 77) after >3 previous lines of therapy in Germany. Cilta-cel, compared with ide-cel, demonstrated superior outcomes, achieving a higher overall response rate (94% vs 82%) and 10-month progression-free survival (PFS; 76% vs 47%). Cilta-cel also led to higher complete response (CR; 61% vs 39%) and improved response conversion, with more patients achieving CR after starting from less than CR before chimeric antigen receptor T-cell (CAR T) therapy. For those attaining CR after therapy, cilta-cel showed longer PFS, especially in patients who entered treatment with a partial response or worse. Cytokine release syndrome was observed in 85% of cilta-cel and 81% of ide-cel cases, predominantly low grade. Immune effector cell-associated neurotoxicity syndrome was more common with cilta-cel (25% vs 15%), although nonrelapse mortality at 10 months was comparable between therapies (7% vs 5%). Weighted multivariable analysis after propensity score matching confirmed a significant advantage in terms of PFS for cilta-cel, with a hazard ratio of 0.48. Overall, outcomes in our registry analysis were comparable with the pivotal trials that led to approval of the respective agents. Cilta-cel demonstrated a greater capacity for response conversion and durable remission. These findings underscore the need for individualized CAR T therapy selection to optimize patient outcomes.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1677-1686"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282369","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":"Foxo1 unlocks the liver endothelial code to iron sensing.","authors":"Kostas Pantopoulos","doi":"10.1182/blood.2025030281","DOIUrl":"https://doi.org/10.1182/blood.2025030281","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"14 1","pages":"1639-1641"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203947","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":"DRiving STandard-of-care CAR T cells in real-world Germany.","authors":"Mark R Dowling,Simon J Harrison","doi":"10.1182/blood.2025029932","DOIUrl":"https://doi.org/10.1182/blood.2025029932","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"157 1","pages":"1634-1635"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203948","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":"AML halts neutrophil maturation.","authors":"Lakshmi Sandhow, Diana Passaro","doi":"10.1182/blood.2025030403","DOIUrl":"https://doi.org/10.1182/blood.2025030403","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"146 14","pages":"1638-1639"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205539","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":"In low-risk myelodysplastic syndrome, don't shoot the STAG2.","authors":"Natasha Szuber,Lambert Busque","doi":"10.1182/blood.2025030114","DOIUrl":"https://doi.org/10.1182/blood.2025030114","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"2 1","pages":"1636-1638"},"PeriodicalIF":20.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203949","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":"Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial.","authors":"Davide Matino, Andrew Palladino, Carrie Turich Taylor, Eunhee Hwang, Sangeeta Raje, Satyaprakash Nayak, Regina McDonald, Suchitra S Acharya, Johnny Mahlangu, Victor Jiménez-Yuste, Nirmalkumar Choraria, Renchi Yang, Chi-Kong Li, Murtadha Al-Khabori, Yasser Wali, Javier Morales Adrián, Young-Shil Park, O Bülent Zülfikar, John Teeter","doi":"10.1182/blood.2024027468","DOIUrl":"10.1182/blood.2024027468","url":null,"abstract":"<p><strong>Abstract: </strong>Marstacimab targets the tissue factor pathway inhibitor to rebalance hemostasis. Previous phase 1 and 2 trials established marstacimab safety and efficacy in adults with severe hemophilia A (HA) or B (HB). BASIS is an open-label, marstacimab phase 3 trial in males aged 12 to 74 years with severe HA (factor VIII <1%) or moderately severe to severe HB (factor IX ≤2%). Participants without inhibitors received on-demand (OD) or routine prophylaxis (RP) therapy during a 6-month observational phase (OP) before receiving once-weekly subcutaneous 150 mg marstacimab during a 12-month active treatment phase (ATP). Primary end points were annualized bleeding rate (ABR) for treated bleeds vs previous OD or RP during the OP, and safety. Of 128 participants enrolled in the OP, 116 received marstacimab in the ATP. In the OD group (n = 33), mean ABR decreased from 39.86 (95% confidence interval [CI], 33.05-48.07) in the OP to 3.20 (95% CI, 2.10-4.88) in the ATP, demonstrating superiority of marstacimab (estimated ABR ratio, 0.080 [95% CI, 0.057-0.113]; P < .0001). In the RP group (n = 83), mean ABR decreased from 7.90 (95% CI, 5.14-10.66) in the OP to 5.09 (95% CI, 3.40-6.78) in the ATP, demonstrating noninferiority and superiority of marstacimab (estimated ABR difference, -2.81 [95% CI, -5.42 to -0.20]; P = .0349). There were no deaths or thromboembolic events. Weekly subcutaneous marstacimab reduced ABR vs OD or RP therapy in the OP in individuals with severe HA or moderately severe to severe HB without inhibitors. Marstacimab was safe and well tolerated with no unanticipated side effects. This trial was registered at www.clinicaltrials.gov as #NCT03938792.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1654-1663"},"PeriodicalIF":23.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559141","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":"Domain and Residue Mapping of Autoantibodies to β2GPI Reveals Differences Among Antiphospholipid Syndrome Phenotypes.","authors":"Suresh Kumar,Deepesh Vaid,Paola Adele Lonati,Arianna Da Via,Marta Tonello,Pier Luigi Luigi Meroni,Vittorio Pengo,Nicola Pozzi","doi":"10.1182/blood.2025029488","DOIUrl":"https://doi.org/10.1182/blood.2025029488","url":null,"abstract":"Antiphospholipid antibodies targeting b2-glycoprotein I (b2GPI) are a hallmark of antiphospholipid syndrome (APS), associated with an increased risk of thrombosis and pregnancy morbidity. Among these, antibodies targeting Domain I (DI) are common in individuals at higher risk; however, their epitopes and prevalence among APS phenotypes remain unclear. Here, we employ a large collection of 29 structurally and functionally validated b2GPI variants to provide new insights into the molecular mechanisms of autoantibody recognition in APS. Using the prototypic human-derived monoclonal anti-DI antibody MBB2, we identified positively charged residue R39 as the key driver for MBB2 binding, followed by residues R43, N56, and T57. Structural analyses revealed that, while R39 is solvent-exposed, R43 is not, as it is caged by residues N56 and T57. The narrow epitope footprint explains why MBB2 exhibits a modest affinity for soluble b2GPI. The cage structure accounts for the epitope being conformational rather than linear. Mutational analyses of IgG anti-b2GPI antibodies from 52 triple-positive APS patients, 37 with a history of thrombosis and 15 non-vascular obstetric patients, confirmed significant reactivity against DI and showed signatures of two conformational epitopes: one similar to MBB2 (epitope I), in which the presence of R39 is essential, and another that does not require R39 (epitope II). While less frequent than epitope-II in our cohort, epitope-I reactivity was notably enriched in thrombotic obstetric patients. Varying epitope specificities for DI may therefore aid in identifying different APS phenotypes and predicting clinical outcomes.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"20 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203619","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":"Mucosal calprotectin is associated with severity of aGI-GVHD and poor outcomes after allogeneic stem cell transplantation.","authors":"Ekin Ece Gurer Kluge,Elisabeth Meedt,Julia Feicht,Kedi Cao,Andreas Hiergeist,Andreas Mamilos,Daniela Hirsch,Matthias Hoepting,Anna-Sophia Kattner,Carina Matos,Sigrid Bülow,Erik Thiele Orberg,Philipp Beckhove,Arne Kandulski,Matthias Evert,Kai Hildner,Marina Kreutz,Matthias Edinger,Daniel Wolff,Wolfgang Herr,Hendrik Poeck,André Gessner,Daniela Andrea Weber,Birte Kehr,Ernst Holler,Sakhila Ghimire","doi":"10.1182/blood.2025029402","DOIUrl":"https://doi.org/10.1182/blood.2025029402","url":null,"abstract":"Calprotectin, a calcium- and zinc-binding protein composed of the subunits S100A8 and S100A9, has been extensively studied as a biomarker of gastrointestinal (GI) inflammation through fecal and serum analyses. However, its role in intestinal tissue remains poorly understood due to limited availability of biopsies. In this study, we analyzed S100A8 and S100A9 mRNA expression in 579 intestinal biopsies from allogeneic stem cell transplant (ASCT) patients and observed a strong association with acute GI graft-versus-host disease (aGI-GvHD) (p<0.001). Neutrophil infiltration correlated with the severity of aGI-GvHD (p<0.001), and calprotectin expression was strongly linked to Toll-like receptor 4 (TLR4) (p<0.001) and TLR2 (p<0.001) expression. TLR4 and aGI-GvHD were associated with elevated calprotectin mRNA levels (p<0.001). When patients received broad-spectrum antibiotics at disease onset, expression of calprotectin was suppressed (S100A8, p=0.001; S100A9, p=0.01). Gastrointestinal site-specific differences in calprotectin expression were identified: during severe aGI-GvHD, levels increased up to 30-fold in the small intestine and up to 5-fold in the large intestine with respect to mild/no aGI-GVHD, while under homeostasis, the large intestine exhibited higher baseline calprotectin (p=0.001). The high clinical relevance is evident from the observation that calprotectin expression was prognostic for transplant-related mortality (TRM). Our study suggests that (a) calprotectin is a potential biopsy biomarker in aGI-GvHD, (b) calprotectin expression and neutrophil infiltration possibly indicate translocation of microbiota, which (c) may be modulated by antibiotics.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"101 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203617","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 single-cell atlas of bone marrow B cells reveals defective central B-cell tolerance in immune thrombocytopenia.","authors":"Zi Sheng,Nan Jiang,Yan Gao,Yuhan Zhang,Xiaoyu Zhang,Nailin Li,Qi Feng,Yanqi Zhang,Limei Wang,John W Semple,Shuwen Wang,Song Li,Jun Peng","doi":"10.1182/blood.2025028960","DOIUrl":"https://doi.org/10.1182/blood.2025028960","url":null,"abstract":"Immune thrombocytopenia (ITP) is characterized by overproduction of anti-platelet autoantibodies. While B-cell depletion therapies show promise in ITP, their high relapse rates suggest a potential de novo breakdown of tolerance during an early stage of B cell development. Here, we investigated how central B-cell tolerance mechanisms affect autoantibody production in ITP. Paired single-cell RNA/B cell receptor (BCR) sequencing and bulk BCR sequencing revealed reduced V-J genomic distances in immunoglobulin kappa-chain (IGK) genes within bone marrow and peripheral B cells from ITP patients, along with decreased expression of recombination activating gene (RAG) in the immature B cells, suggesting insufficient receptor editing. Single-cell antibody cloning demonstrated increased autoreactive and polyreactive naïve B cells in ITP, indicating defective central B-cell tolerance. Through in vivo study, we established a causal link between receptor editing defects and anti-platelet antibody production, validating the immature B cell stage as the key phase of dysregulation. These findings suggest that insufficient receptor editing of immature B cells triggers central B-cell tolerance deficiency and autoantibody accumulation in ITP.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"9 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203621","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}