Blood advances最新文献

{"title":"The differential expression of circulating microRNAs in sickle cell trait compared with the normal hemoglobin phenotype.","authors":"Kabir Olaniran, Ronak Lakhia, Scott Krinsky, Sagar Nigwekar, Susan Hedayati","doi":"10.1182/bloodadvances.2024015312","DOIUrl":"10.1182/bloodadvances.2024015312","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3350-3355"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging radiotherapy before chimeric antigen receptor T cells for B-cell lymphomas: an ILROG multicenter study.","authors":"Nikhil Yegya-Raman, John P Plastaras, Christopher M Wright, Monica Chelius, Siqi Zhang, Jonathan A Baron, Harper Hubbeling, Austin J Sim, Timothy J Robinson, Michael D Jain, Brandon Imber, Beatrice Fregonese, Joachim Yahalom, Colton Ladbury, Savita Dandapani, Chelsea C Pinnix, Jillian R Gunther, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Joanna C Yang, Jessica Chew, Steve Braunstein, Sumi Sinha, Nathan M Delinger, Susan Sun, Stephanie A Terezakis, Gukan Sakthivel, Louis S Constine, Amit K Chowdhry, Patrick M Reagan, Skyler Burke, Yolanda D Tseng, Michael J LaRiviere, Amit Maity, Stephen J Schuster, Elise A Chong, Nicholas B Figura","doi":"10.1182/bloodadvances.2025015855","DOIUrl":"10.1182/bloodadvances.2025015855","url":null,"abstract":"<p><strong>Abstract: </strong>Despite the increasing utilization of bridging radiotherapy (Br-RT), its impact on chimeric antigen receptor T-cell therapy (CAR-T) efficacy and toxicity remains poorly characterized. We retrospectively reviewed patients with relapsed/refractory B-cell lymphomas (BCLs) who received Br-RT followed by CAR-T from 2018 to 2020 across 10 institutions. Br-RT toxicities were graded per Common Terminology Criteria for Adverse Events version 5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy Consensus Guidelines. One hundred seventy-two patients (168 large BCL) received Br-RT before axicabtagene ciloleucel (73%), tisagenlecleucel (24%), or brexucabtagene autoleucel (2%). At leukapheresis, most patients (74%) had advanced-stage disease and 39% had bulky disease measuring ≥10cm. Comprehensive Br-RT was administered to 39% and bridging systemic therapy to 35%. Among all patients, grade ≥3 Br-RT toxicity occurred in 2% (1 grade 5 toxicity), grade ≥3 CRS in 9%, and grade ≥3 ICANS in 24%. Median follow-up was 31.3 months. Two-year progression-free survival (PFS) and overall survival (OS) were 38% and 53%, respectively. On multivariable analysis, comprehensive Br-RT was associated with superior PFS (hazard ratio [HR], 0.38; P < .001) and OS (HR, 0.48; P = .011). Patients with lactate dehydrogenase (LDH) normalization after Br-RT (high pre-Br-RT LDH, normal post-Br-RT LDH) had superior PFS and OS compared with those with high post-Br-RT LDH and similar PFS and OS compared with those with normal baseline LDH. In this particularly high-risk cohort, Br-RT before CAR-T demonstrates an acceptable toxicity profile with favorable clinical outcomes compared with historical controls. Comprehensive Br-RT and LDH normalization after Br-RT may be associated with superior PFS and OS.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3293-3303"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic use: impact on the microbiome and cellular therapy outcomes.","authors":"Alicia Darwin, Jiayi Xie, Melody Smith","doi":"10.1182/bloodadvances.2024013809","DOIUrl":"10.1182/bloodadvances.2024013809","url":null,"abstract":"<p><strong>Abstract: </strong>Antibiotics disrupt the delicate balance of bacteria, fungi, and viruses in the human microbiome. Growing evidence indicates a significant relationship between the intestinal microbiome and cellular therapy, which aligns with the established influence of the microbiome on immune responses. When examining the link between cellular therapy and the microbiome, it is essential to understand how disruptions in the microbiome, especially those caused by antibiotics, affect these therapies. Here, we discuss the impact of antibiotics on the intestinal microbiome, cellular therapy outcomes, and associated toxicities, particularly in the context of hematopoietic cell transplantation and chimeric antigen receptor T-cell therapy. Furthermore, we examine the mechanisms through which antibiotics affect cellular therapy, the future implications of this knowledge, and the areas that warrant further investigation.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3356-3367"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepancy between original and adapted ASH VTE guidelines: same clinical evidence but different recommendations.","authors":"Suely Meireles Rezende, Ignacio Neumann, Benjamim Djulbegovic","doi":"10.1182/bloodadvances.2025016102","DOIUrl":"10.1182/bloodadvances.2025016102","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3182-3189"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients with AML and an IDH2-R172 mutation exhibit a unique initial response to intensive chemotherapy induction.","authors":"Meira Yisraeli Salman, Alexander R Terry, Andriy Derkach, David Nemirovsky, Kuo-Kai Chin, Yannis K Valtis, Leora Boussi, Theresa Spivey, Wenbin Xiao, Christopher Famulare, Jenna Ciervo, Jacob M Rowe, Martin S Tallman, Eytan M Stein","doi":"10.1182/bloodadvances.2024015324","DOIUrl":"10.1182/bloodadvances.2024015324","url":null,"abstract":"<p><strong>Abstract: </strong>The utility of a midcycle bone marrow biopsy (BMB) for early assessment of response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there is little consideration as to the possibility of different response dynamics among genetically defined subgroups. Clinical observations led to the hypothesis that patients with AML and mutations in IDH2-R172 (R172-m) exhibit particularly slow blast reduction after IC induction. The purpose of this study was to analyze response kinetics of patients with R172-m to IC and compare the dynamics to patients with AML and IDH2-R140 mutations (R140-m). A retrospective single-center analysis was conducted among patients with newly diagnosed IDH2-mutated AML who received IC induction. Dynamics of blast reduction were compared and correlated with outcomes. A total of 52 patients were identified; 33 with R140-m and 19 with R172-m. Patients with R172-m had significantly higher midcycle BMB median blast count (70% vs 5%; P < .001), and their BMBs were slightly more cellular (P = .045). Among the R140-m, 58% had ≤5% blasts vs 0 of the R172-m. Furthermore, it took significantly longer for patients with R172-m to achieve blast clearance (≤5% blasts in BMB) compared to those with R140-m (P = .017). However, there was no difference in overall survival between the 2 groups, and outcomes were similar and favorable. This type of slow blast reduction has only previously been described in patients with acute promyelocytic leukemia. These findings suggest judicial application of reinduction strategies in this subgroup and warrant further investigation.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3213-3222"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of peripheral neuropathy in the POLARIX study using clinician- and patient-reported outcomes.","authors":"Marek Trněný, Laura Fogliatto, Faithlore Gardner, Ian Flinn, Jean-François Larouche, Corinne Haioun, Miguel Canales, Hideki Goto, Roman Hajek, Gilles Salles, Avrita Singh, Mark Yan, Rucha Kothari, Gabriel Man, Deniz Sahin, Jamie Hirata, Calvin Lee, Hervé Tilly, Christopher R Flowers","doi":"10.1182/bloodadvances.2024014695","DOIUrl":"10.1182/bloodadvances.2024014695","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3263-3267"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-based risk stratification of myeloid neoplasms harboring TP53 mutations.","authors":"Mithun Vinod Shah, Kevin Hung, Anmol Baranwal, Monika M Kutyna, Aref Al-Kali, Carla Toop, Patricia Greipp, Anna Brown, Syed Shah, Shreyas Khanna, Dariusz Ladon, Vedavyas Gannamani, Dong Chen, Kebede Begna, Zoe K Price, Danielle Rud, Mark R Litzow, William J Hogan, Peter Bardy, Talha Badar, Sharad Kumar, David T Yeung, Mrinal M Patnaik, James M Foran, Rong He, Naseema Gangat, Hamish S Scott, Cecilia Y Arana Yi, Hassan Alkhateeb, Abhishek A Mangaonkar, Daniel Thomas, Christopher N Hahn, Attilio Orazi, Daniel A Arber, Chung Hoow Kok, Ayalew Tefferi, Devendra Hiwase","doi":"10.1182/bloodadvances.2024015238","DOIUrl":"10.1182/bloodadvances.2024015238","url":null,"abstract":"<p><strong>Abstract: </strong>This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3370-3380"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of factor VIII in zebrafish rebalances antithrombin deficiency but has a limited bleeding diathesis.","authors":"Azhwar Raghunath, Catherine E Richter, Megan S Griffin, Sylvia M Emly, Murat Yaman, Valder R Arruda, Benjamin J Samelson-Jones, Jordan A Shavit","doi":"10.1182/bloodadvances.2024013143","DOIUrl":"10.1182/bloodadvances.2024013143","url":null,"abstract":"<p><strong>Abstract: </strong>Deficiencies in coagulation factor VIII (FVIII, F8) result in the bleeding disorder hemophilia A. An emerging novel therapeutic strategy for bleeding disorders is to enhance hemostasis by limiting natural anticoagulants, such as antithrombin (AT3). To study pro/anticoagulant hemostatic balance in an in vivo model, we used genome editing to create null alleles for f8 and von Willebrand factor (vwf) in zebrafish, a model organism with a high degree of homology to the mammalian hemostatic system and unique attributes, including external development and optical transparency. f8 homozygous mutant larvae surprisingly formed normal thrombi when subjected to laser-mediated endothelial injury, had no overt signs of hemorrhage, although they did have a modest increase in mortality. We have previously shown that at3-/- larvae develop disseminated intravascular coagulation (DIC), with spontaneous thrombosis and fibrinogen consumption, resulting in a bleeding phenotype marked by secondary lack of induced thrombus formation upon endothelial injury. We found that with loss of FVIII (f8-/-;at3-/-), larvae no longer developed spontaneous fibrin thrombi and produced clots in response to endothelial injury. In contrast, homozygous loss of zebrafish Vwf failed to rescue the at3 DIC phenotype. These findings demonstrate an altered balance of natural anticoagulants that mitigates FVIII deficiency in zebrafish, similar to hemostatic drugs in the clinical development pipeline, and suggest that zebrafish FVIII might circulate independently of Vwf. Further exploration of this unique balance in zebrafish could provide novel insights into the treatment of hemophilia A and von Willebrand disease.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3136-3148"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Canagliflozin may increase thromboembolic events in males with erythrocytosis but not in females.","authors":"Yohei Doi, Takayuki Hamano, Osamu Yamaguchi, Yoshitaka Isaka","doi":"10.1182/bloodadvances.2025016320","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016320","url":null,"abstract":"<p><strong>Abstract: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly recognized as a common cause of drug-induced erythrocytosis. SGLT2 inhibitor-induced erythropoiesis may increase blood viscosity and precipitate thromboembolism, particularly in patients with preexisting erythrocytosis. We conducted a post hoc pooled analysis of patient-level data from the randomized, double-blind, placebo-controlled Canagliflozin Cardiovascular Assessment Study program and the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial, which assessed the safety and efficacy of canagliflozin in patients with type 2 diabetes mellitus. The primary outcome, a composite of myocardial infarction (MI), stroke, and any thromboembolism, was evaluated using sex-specific Cox models, with baseline hematocrit as an effect modifier. Among participants with available baseline hematocrit values (98.5% [14 321/14 543]), 35% were female. Canagliflozin significantly increased hematocrit levels compared with placebo even in patients with erythrocytosis (males > 49%; females > 48%) and increased the proportion of individuals with erythrocytosis at 1 year (males, 16.9% vs 5.5%; females, 5.2% vs 1.0%). Overall, canagliflozin did not alter the risk of the primary outcome in either males or females. However, in males, baseline hematocrit levels modified the treatment effect on the primary outcome, whether assessed categorically (anemia, normal, and erythrocytosis) or continuously with fractional polynomial (FP) analysis (P interaction < .05). FP analysis showed treatment benefits in anemic males but show harm in those with erythrocytosis, primarily driven by an increased risk of MI. Meanwhile, no heterogeneity was seen in females for these outcomes. In conclusion, canagliflozin may pose a safety concern for thromboembolism in males with erythrocytosis at baseline, warranting further investigations. These trials were registered at www.ClinicalTrials.gov as #NCT01032629, #NCT01989754, and #NCT02065791.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 13","pages":"3202-3212"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583142","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":"Immunological consequences of CAR T-cell therapy: an analysis of infectious complications and immune reconstitution.","authors":"Andreas Riedel, Laurent Phely, Stefan Hug, Philipp Faustmann, Jan Christian Schroeder, Britta Besemer, Anna M Paczulla Stanger, Christoph Faul, Claudia Lengerke, Jan Frederic Weller, Wolfgang Bethge","doi":"10.1182/bloodadvances.2024015346","DOIUrl":"10.1182/bloodadvances.2024015346","url":null,"abstract":"<p><strong>Abstract: </strong>Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in treating relapsed and refractory (R/R) B-cell neoplasms, such as diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Despite its success, the long-term effects and sequelae of CAR T cells on the immune system remain underexplored. This study presents a 1-year follow-up analysis of 52 patients (42 with R/R DLBCL and 10 with R/R MM) treated with anti-CD19- and B-cell maturation antigen-targeted CAR T cells, focusing on immune reconstitution and infectious complications. Our findings reveal that CAR T-cell therapy leads to profound depletion of B and T cells. CD4+ T cells and CD19+ B cells exhibited impaired regeneration after treatment. Infections were more frequent during the first 30 days. In the short-term follow-up, density of infections within 100 days at risk was 1.8 in patients with DLBCL and 4.6 in patients with MM, with bacterial infections predominating in this early period after CAR T-cell infusion. In addition, we observed a shift to viral infections in the long-term follow-up, alongside with a decline in infection density to 0.1 in patients with DLBCL and 0.4 infections per 100 days at risk in patients with MM, respectively. Severe cytokine release syndrome was associated with a higher risk of late-onset infections. These findings highlight the importance of close monitoring and prophylactic measures in patients undergoing CAR T-cell therapy to reduce infection risks and enhance immune recovery.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3149-3158"},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12242403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}