Blood最新文献

{"title":"Eliminating The Need for Sequential Confirmation of Response in Multiple Myeloma.","authors":"Jean-Sébastien Claveau, Prashant Kapoor, Moritz Binder, Francis K Buadi, David Dingli, Angela Dispenzieri, Amie L Fonder, Morie A Gertz, Wilson I Gonsalves, Suzanne R Hayman, Miriam A Hobbs, Lisa Hwa Christenson, Taxiarchis V Kourelis, Martha Q Lacy, Nelson Leung, Yi Lin, Rahma Warsame, Robert A Kyle, S Vincent Rajkumar, Shaji K Kumar","doi":"10.1182/blood.2024027949","DOIUrl":"https://doi.org/10.1182/blood.2024027949","url":null,"abstract":"<p><p>Disease response and progression assessment in multiple myeloma (MM) is based on various measurements of monoclonal protein (serum and urine protein electrophoresis, serum free light chain (FLC, and or quantitative immunoglobulins). Currently, the IMWG consensus response criteria require two sequential assessments of any one marker made at any time before confirmation of disease progression and the institution of any new therapy. However, this can be cumbersome in clinical trials. Herein, we hypothesized that if two markers meet the progression criteria simultaneously, a repeat of either will not be necessary for confirmation. We retrospectively studied all sequential patients with myeloma enrolled in clinical trials at Mayo Clinic. We identified 583 episodes of confirmed progression in our study. Among the 583 progression episodes, nearly 70% (sensitivity of the simultaneous criteria) met the two simultaneous variable criteria at the first testing, indicating progression. Conversely, among 413 patients who met progression criteria by two simultaneous values, 98% (specificity of the simultaneous criteria) of patients subsequently had confirmed progression by sequential values. In summary, for patients with two disease burden markers meeting the simultaneous progression criteria, sequential assessment either one for confirmation may not be necessary to determine disease progression.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257320","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 in GVHD and GVL after hematopoietic stem cell transplantation for myeloid malignancies.","authors":"Gérard Socié","doi":"10.1182/blood.2025028617","DOIUrl":"https://doi.org/10.1182/blood.2025028617","url":null,"abstract":"<p><p>Although allogeneic HCT is a leading treatment approach for myeloid malignancies, challenges in its immune biology and in treatment approaches remain. In the past decade major advances in the knowledge of mechanisms of graft-versus host disease (GvHD) has allowed development of new treatments both for GvHD prophylaxis and treatment. However, although successes did occur, failure did as well. Reasons for failure can be linked either to incomplete understanding of the pathophysiology of GVHD, or, in some cases, to errors in the design of clinical trials. Better GVHD prophylaxes and disease control have likely led to decreased non relapse mortality (NRM). However, while NRM rates have decreased, rates of relapse of the original malignancy have not significantly improved. Our current understanding of the biology of the graft-versus leukemia effect (GvL) still lag beyond that of GvHD, and treatment approaches to manipulate the GvL effect remain limited. The reasons for such a lag are numerous, but improved knowledge of the biology of hematological malignancies open the gate to new developments, providing that we can better understand the interplay between the immune system with leukemic clones. From a therapeutical perspective, much attention has been paid to the results from randomized clinical trials and from a biological perspective on recent discoveries, especially in the human setting. The objective of this perspective is to analyze what are the current challenges in the biology and treatment of GvHD and GvL and to provide a personal view on how some biological and therapeutic issues could be approached.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257319","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 sweet business of VWF clearance.","authors":"Renhao Li, Robert F Sidonio","doi":"10.1182/blood.2025029022","DOIUrl":"https://doi.org/10.1182/blood.2025029022","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 23","pages":"2680-2681"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224222","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":"Outcomes among adult recipients of CAR T-cell therapy for Burkitt lymphoma.","authors":"Laura Samples, Hossein Sadrzadeh, Matthew J Frigault, Caron A Jacobson, Mehdi Hamadani, Ashwath Gurumurthi, Paolo Strati, Roni Shouval, Ariela Noy, Peter A Riedell, Saurabh Dahiya, David G Maloney, Brian G Till, Alexandre V Hirayama, Jordan Gauthier, Ajay K Gopal, Stephen D Smith, Christina Poh, Ryan Lynch, Chaitra Ujjani, Mengyang Di, Vikram Raghunathan, Mehrdad Shakib-Azar, Kikkeri N Naresh, Ted A Gooley, Jean Yared, Michael D Jain, Frederick L Locke, Lori Ann Leslie, Narendranath Epperla, Monalisa Ghosh, Alan Skarbnik, Brian T Hill, Manali K Kamdar, Valentin Ortiz-Maldonado, Nuria Martinez-Cibrian, Leyla Shune, Mazyar Shadman","doi":"10.1182/blood.2024026831","DOIUrl":"10.1182/blood.2024026831","url":null,"abstract":"<p><strong>Abstract: </strong>Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that is associated with poor outcomes in patients with relapsed/refractory disease. This multicenter, retrospective study evaluated real-world CD19 chimeric antigen receptor (CAR) T-cell therapy outcomes in patients with relapsed/refractory BL using data abstracted from the medical records. In total, 31 patients received CAR T cells after a median of 3 previous therapies (range, 1-6). Patients received axicabtagene ciloleucel (n = 19), lisocabtagene maraleucel (n = 4), tisagenlecleucel (n = 4), or other agents (n = 4). Grade 1 to 2 cytokine release syndrome occurred in 83.9% of patients (grade ≥3, 65%), and grade 1 to 2 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 29% of patients (grade ≥3, 19.4%). The 28-day mortality rate was 16.1%, including 1 patient who died from grade 5 ICANS. The overall response rate at 1 month was 58.0% with a complete response (CR) rate of 41.9%; however, the 6-month CR rate was only 19.4%. The median progression-free survival was 2.3 months (95% confidence interval, 1.0-9.0), and the median overall survival was 6.0 months (95% confidence interval, 1.9-11.5). Three patients (9.7%) received consolidative allogeneic stem cell transplants, but all subsequently relapsed. In conclusion, CD19 CAR T-cell therapy infrequently delivers long-term disease control in BL. Further investigation is needed to determine the most effective alternative management strategy for these patients.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2762-2767"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405369","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":"Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome.","authors":"Changya Chen, Jason Xu, Jonathan H Sussman, Tiffaney Vincent, Joseph S Tumulty, Satoshi Yoshimura, Fatemeh Alikarami, Wenbao Yu, Yang-Yang Ding, Chia-Hui Chen, Elizabeth Y Li, Austin Yang, Xiaohuan Qin, Shovik Bandyopadhyay, Jacqueline Peng, Petri Pölönen, Haley Newman, Brent L Wood, Jianzhong Hu, Rawan Shraim, Andrew D Hughes, Caroline Diorio, Lahari Uppuluri, Gongping Shi, Theresa Ryan, Tori Fuller, Mignon L Loh, Elizabeth A Raetz, Stephen P Hunger, Stanley B Pounds, Charles G Mullighan, David Frank, Jun J Yang, Kathrin M Bernt, David T Teachey, Kai Tan","doi":"10.1182/blood.2024027270","DOIUrl":"10.1182/blood.2024027270","url":null,"abstract":"<p><strong>Abstract: </strong>The critical role of leukemia-initiating cells as a therapy-resistant population in myeloid leukemia is well established. However, the molecular signatures of such cells in acute lymphoblastic leukemia remain underexplored. Moreover, their role in therapy response and patient prognosis is yet to be systematically investigated across various types of acute leukemia. We used single-cell multiomics to analyze diagnostic specimens from 96 pediatric patients with acute lymphoblastic, myeloid, and lineage-ambiguous leukemias. Through the integration of single-cell multiomics with extensive bulk RNA sequencing and clinical data sets, we uncovered a prevalent, chemotherapy-resistant subpopulation that resembles hematopoietic stem and progenitor cells (HSPC-like) and is associated with poor clinical outcomes across all subtypes investigated. We identified a core transcriptional regulatory network (TRN) in HSPC-like blasts that is combinatorially controlled by HOXA/AP1/CEBPA. This TRN signature can predict chemotherapy response and long-term clinical outcomes. We identified shared potential therapeutic targets against HSPC-like blasts, including FLT3, BCL2, and the PI3K pathway. Our study provides a framework for linking intratumoral heterogeneity with therapy response, patient outcomes, and the discovery of new therapeutic targets for pediatric acute leukemias.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2685-2700"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639668","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":"Enhanced α2-3-linked sialylation determines the extended half-life of CHO-rVWF.","authors":"Ciara Byrne, Soracha Ward, Jamie O'Sullivan, Alain Chion, Patricia Lopes, Bogdan Baci, Caoimhe Dowd, Darragh Jordan, Ross Baker, Roger J S Preston, Marco Monopoli, Peter L Turecek, Maximilianos Kotsias, Jack Cheeseman, Alan B Moran, Richard A Gardner, Daniel I R Spencer, Ferdows Atiq, James S O'Donnell","doi":"10.1182/blood.2024027038","DOIUrl":"10.1182/blood.2024027038","url":null,"abstract":"<p><strong>Abstract: </strong>The half-life of recombinant human von Willebrand factor (rVWF) expressed in CHO cells (CHO-rVWF; Vonicog alfa; and Vonvendi/Veyvondi) is significantly longer than that of plasma-derived VWF (pdVWF). This finding is intriguing because CHO cells do not generate α2-6 sialylation, which constitutes the majority of human pdVWF sialylation. We hypothesized that glycan differences might regulate the longer half-life of CHO-rVWF. In lectin plate-binding assays and liquid chromatography-mass spectrometry analysis, we confirmed that CHO-rVWF lacked α2-6-linked sialylation. Conversely, however, α2-3-linked sialylation was significantly increased on CHO-rVWF, which also had reduced exposed β-galactose (β-Gal) compared to pdVWF. Consistent with human data, CHO-rVWF clearance was significantly (P < .001) reduced in VWF-/- mice compared to pdVWF. However, clearance of asialo-pdVWF and asialo-CHO-rVWF were identical. In keeping with the in vivo half-life prolongation, CHO-rVWF binding to murine macrophages (P = .012) and HepG2 cells (P = .001) was significantly decreased compared to pdVWF. Furthermore, CHO-rVWF binding to purified macrophage-galactose-type lectin (MGL) receptor and asialoglycoprotein receptor (ASGPR) was also significantly reduced. In contrast to pdVWF, in vivo studies in MGL1-/- mice and Asgr1-/- mice demonstrated that neither MGL nor ASGPR plays significant roles in regulating CHO-rVWF clearance. Together, our findings demonstrate that enhanced α2-3-linked sialylation on CHO-rVWF is responsible for its extended half-life.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2768-2773"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656091","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":"A great mitigator of non-ICANS neurotoxicities?","authors":"Jasia Mahdi","doi":"10.1182/blood.2025029233","DOIUrl":"https://doi.org/10.1182/blood.2025029233","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 23","pages":"2682-2684"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224215","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":"Getting to the root of high-risk leukemias.","authors":"Michael Poeschla, Vijay G Sankaran","doi":"10.1182/blood.2025029069","DOIUrl":"https://doi.org/10.1182/blood.2025029069","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 23","pages":"2673-2674"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224219","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":"MURANO's final conclusions: what we've learned, what's next?","authors":"Othman Al-Sawaf","doi":"10.1182/blood.2025028678","DOIUrl":"https://doi.org/10.1182/blood.2025028678","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 23","pages":"2674-2676"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224220","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":"Novel regulators of GVHD revealed through microbiome and metabolome patterns across distinct intestinal regions.","authors":"Emma Lauder, Erik Anders Kiledal, Laure Maneix, Teal Furnholm, Ana Santibanez, Dongchang Zhao, Yaping Sun, Gregory J Dick, Pavan Reddy","doi":"10.1182/blood.2024025924","DOIUrl":"10.1182/blood.2024025924","url":null,"abstract":"<p><strong>Abstract: </strong>Microbial dysbiosis and metabolite changes in the gastrointestinal (GI) tract have been linked to pathogenesis and severity of many diseases, including graft-versus-host disease (GVHD), the major complication of allogeneic hematopoietic stem cell transplantation. However, published studies have only considered the microbiome and metabolome of excreted stool and do not provide insight into the variability of the microbial community and metabolite composition throughout the GI tract or the unique temporal dynamics associated with different gut locations. Because such geographical variations are known to influence disease processes, we used a multi-omics approach to characterize the microbiome and metabolite profiles of gut contents from different intestinal regions in well-characterized mouse models of GVHD. Our analysis validated analyses from excreted stool, but importantly, uncovered new biological insights from the microbial and metabolite changes between syngeneic and allogeneic hosts that varied by GI location and time after transplantation. Our integrated analysis confirmed the involvement of known metabolic pathways, including short-chain fatty acid synthesis and bile acid metabolism, and identified additional functional genes, pathways, and metabolites, such as amino acids, fatty acids, and sphingolipids, linked to GI GVHD. Finally, we validated a biological relevance for one such newly identified microbial metabolite, phenyl lactate, that heretofore had not been linked to GI GVHD. Thus, our analysis of the geographic variability in the intestinal microbiome and metabolome offers new insights into GI GVHD pathogenesis and potential for novel therapeutics.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2774-2787"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514608","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}