Blood最新文献_第2页

A great mitigator of non-ICANS neurotoxicities? 非icans神经毒性的有效缓解剂？

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2025029233

Jasia Mahdi

引用次数: 0

Getting to the root of high-risk leukemias. 探究高危白血病的根源。

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2025029069

Michael Poeschla, Vijay G Sankaran

引用次数: 0

MURANO's final conclusions: what we've learned, what's next? 穆拉诺的最终结论是：我们学到了什么，接下来会发生什么？

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2025028678

Othman Al-Sawaf

引用次数: 0

Novel regulators of GVHD revealed through microbiome and metabolome patterns across distinct intestinal regions. 通过不同肠道区域的微生物组和代谢组模式揭示了GVHD的新调节因子。

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2024025924

Emma Lauder, Erik Anders Kiledal, Laure Maneix, Teal Furnholm, Ana Santibanez, Dongchang Zhao, Yaping Sun, Gregory J Dick, Pavan Reddy

{"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":"Abstract: 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.","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}

引用次数: 0

Considerations on the dose and schedule of tyrosine kinase inhibitors for chronic myeloid leukemia: does dose matter? 慢性髓系白血病酪氨酸激酶抑制剂的剂量和治疗方案：剂量重要吗？

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2024027944

Mark Dalgetty, Jorge Cortes

{"title":"Considerations on the dose and schedule of tyrosine kinase inhibitors for chronic myeloid leukemia: does dose matter?","authors":"Mark Dalgetty, Jorge Cortes","doi":"10.1182/blood.2024027944","DOIUrl":"10.1182/blood.2024027944","url":null,"abstract":"Abstract: Tyrosine kinase inhibitors (TKIs) are the mainstay of treatment for patients with chronic myeloid leukemia. The standard dose has been established for each drug according to the indication for the various stages of the disease and whether as initial therapy or after failure of previous therapies. The recommended doses are fixed for all patients and dose adjustments are mostly recommended for management of adverse events. The standard doses have been derived largely from phase 1 studies, but as we discuss in this review, the current model may not be optimal for this purpose for drugs such as TKIs that are meant to be used for extended periods of time. Subsequent studies have led to changes in the initial recommendations for some drugs. In others, experience and real-world data have led to the use of TKIs using doses and adjustments that may be different than what clinical trials have recommended. In other scenarios, available data suggest that the current standard dose may need to be revisited. It may also be time to reconsider the standard approach of starting therapy with the standard dose and adjusting merely based on adverse events. We propose a flexible model that perhaps reflects more accurately what is being done frequently in the clinic.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2701-2708"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656089","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}

引用次数: 0

Cyclophosphamide mitigates non-ICANS neurotoxicities following ciltacabtagene autoleucel treatment. 环磷酰胺减轻非icans神经毒性后，西他他烯自己醇治疗。

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2024028172

Viktoria Blumenberg, Benjamin R Puliafito, Charlotte E Graham, Mark B Leick, Md Raihan Chowdhury, Maxx King, Deshea L Harris, Noopur S Raje, Andrew R Branagan, Andrew J Yee, Diana Cirstea, Kathleen M E Gallagher, Jörg Dietrich, Marcela V Maus, Matthew J Frigault

引用次数: 0

Burkitt lymphoma: click here to add to CAR-T? 伯基特淋巴瘤：点击这里添加CAR-T？

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2025028549

Eliza A Hawkes, Gareth P Gregory

引用次数: 0

The advent of multiomics in experimental transplantation. 实验移植中多组学的出现。

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2024028276

Gerard Socie

引用次数: 0

IL-10 from tumoral B cells modulates the diffuse large B-cell lymphoma microenvironment and response to immunotherapy. 来自肿瘤B细胞的IL-10调节弥漫性大B细胞淋巴瘤微环境和对免疫治疗的反应。

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2024025755

Marcos Garcia-Lacarte, Sara C Grijalba, Javier Melchor, Marién Pascual, Enrique Goñi, Iñigo Clemente-Larramendi, Sandra Morales-Sánchez, María A Burrell, Oscar Blanco, Adrián Arnaiz-Leché, Blanca S Berrozpe, Maria Amann, Christian Klein, Pablo Umaña, Miguel Canales, José Ángel Martínez-Climent, Juan J Lasarte, Pablo Sarobe, Francisco J Novo, Sergio Roa

{"title":"IL-10 from tumoral B cells modulates the diffuse large B-cell lymphoma microenvironment and response to immunotherapy.","authors":"Marcos Garcia-Lacarte, Sara C Grijalba, Javier Melchor, Marién Pascual, Enrique Goñi, Iñigo Clemente-Larramendi, Sandra Morales-Sánchez, María A Burrell, Oscar Blanco, Adrián Arnaiz-Leché, Blanca S Berrozpe, Maria Amann, Christian Klein, Pablo Umaña, Miguel Canales, José Ángel Martínez-Climent, Juan J Lasarte, Pablo Sarobe, Francisco J Novo, Sergio Roa","doi":"10.1182/blood.2024025755","DOIUrl":"10.1182/blood.2024025755","url":null,"abstract":"Abstract: The contribution of interleukin-10 (IL-10), secreted by tumoral B cells, to the progression and shaping of the microenvironment in diffuse large B-cell lymphoma (DLBCL) with activated B-cell-like (ABC) phenotype is not yet completely understood. To shed light on this issue, we generated an immunocompetent mouse model of ABC-DLBCL with conditional knockout of IL-10 specifically in malignant B cells. Paradoxically, these mice had significantly worse overall survival when left untreated but experienced increased sensitivity to conventional anti-CD20 immunotherapy or regulatory T-cell depletion. We identified various immunomodulatory mechanisms involved in this behavior. In particular, we show that IL-10-deficient lymphomas acquire a highly immunosuppressed and T-cell-exhausted microenvironment with increased angiogenesis that results in a more aggressive phenotype, which is refractory to PD-1 immune checkpoint blockade. However, the response of IL-10-deficient mice to anti-CD20 immunotherapy was greatly enhanced by upregulation of calcium channels in B cells. In general, IL-10 autocrine signaling promotes the survival of malignant B cells, whereas the paracrine action of B-cell-derived IL-10 maintains an immunoreactive microenvironment that influences the efficacy of emerging immunotherapy strategies targeting the lymphoma microenvironment. Furthermore, IL-10-associated transcriptional signatures derived from our studies may correctly predict clinical outcomes of patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). Thus, our work provides important functional and mechanistic insights into the role of B-cell-derived IL-10 in the biology of ABC-DLBCL.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2746-2761"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122304","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}

引用次数: 0

The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL. MURANO研究：VenR对复发/难治性CLL患者的最终分析和再治疗/交叉亚研究结果。

IF 21 1区医学

Blood Pub Date : 2025-06-05 DOI: 10.1182/blood.2024025525

Arnon P Kater, Rosemary Harrup, Thomas J Kipps, Barbara Eichhorst, Carolyn J Owen, Sarit Assouline, Nicole Lamanna, Tadeusz Robak, Javier de la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Clemens Mellink, Anton W Langerak, Brenda Chyla, Relja Popovic, Yanwen Jiang, Rosemary Millen, Marcus Lefebure, Maria Thadani-Mulero, Michelle Boyer, John F Seymour

{"title":"The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL.","authors":"Arnon P Kater, Rosemary Harrup, Thomas J Kipps, Barbara Eichhorst, Carolyn J Owen, Sarit Assouline, Nicole Lamanna, Tadeusz Robak, Javier de la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Clemens Mellink, Anton W Langerak, Brenda Chyla, Relja Popovic, Yanwen Jiang, Rosemary Millen, Marcus Lefebure, Maria Thadani-Mulero, Michelle Boyer, John F Seymour","doi":"10.1182/blood.2024025525","DOIUrl":"10.1182/blood.2024025525","url":null,"abstract":"Abstract: Fixed-duration venetoclax-rituximab (VenR) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the phase 3 MURANO trial resulted in superior progression-free survival (PFS) and overall survival (OS) vs bendamustine-rituximab (BR). We report the final analyses of MURANO (median follow-up, 7 years). Patients were randomized to VenR (venetoclax 400 mg daily for 2 years plus monthly rituximab for 6 months; n = 194) or BR (6 months; n = 195). In a substudy, patients with progressive disease (PD) received VenR as retreatment or crossover from BR. At the final data cut (3 August 2022), the median PFS with VenR was 54.7 months vs 17.0 months with BR. The 7-year PFS with VenR was 23.0%. The 7-year OS was 69.6% and 51.0%, respectively. Among VenR-treated patients with undetectable minimal residual disease (MRD; uMRD) and no PD at end of treatment (EOT; n = 83), the median PFS from EOT was 52.5 vs 18.0 months in patients with MRD at EOT (n = 35; P < .0001). Fourteen patients had enduring uMRD. Three distinct mutations in BCL2 in 4 patients were identified. In the substudy, 25 patients were retreated with VenR, and 9 patients crossed over to VenR; the median PFS was 23 and 27 months, and the best overall response rate was 72% and 89%, respectively. At the end of combination treatment (EOCT), after retreatment or crossover, 8 and 6 patients achieved uMRD, respectively. No new safety findings were observed. Overall, these final MURANO analyses support consideration of fixed-duration VenR therapy for patients with relapsed/refractory CLL. This trial was registered at www.clinicaltrials.gov as #NCT02005471.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2733-2745"},"PeriodicalIF":21.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514613","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}

引用次数: 0