Blood advances最新文献

{"title":"Sex and genotype specificities of microvasculature and muscle remodeling in sub-Saharan sickle cell trait and disease.","authors":"Léo Blervaque, Pablo Bartolucci, Manon Riccetti, Marion Ravelojaona, Angèle N Merlet, Mathilde Noguer, Manon Rojo, Christophe Hourdé, Cyril Martin, Vincent Pialoux, Barnabas Gellen, Frédéric Galactéros, Samuel Oyono-Enguéllé, Léonard Féasson, Laurent A Messonnier","doi":"10.1182/bloodadvances.2024015657","DOIUrl":"10.1182/bloodadvances.2024015657","url":null,"abstract":"<p><strong>Abstract: </strong>Sickle cell disease (SCD) is associated with microvascular and muscle remodeling as well as reduced exercise tolerance. However, SCD repercussions on microvasculature and muscle in women remain unknown. This study aimed to compare (1) muscle microvascular and energetic characteristics of female and male healthy individuals (CON), carriers of sickle cell trait (SCT), and patients with SCD; and (2) adaptations to endurance training (ET) compared with habitual life (untrained [UT]) in patients. In SCD, correlations between capillary density and plasma L-selectin and intercellular adhesion molecule and between capillary diameter and mean corpuscular hemoglobin S concentration were noticed (P < .01 all). The capillary network rarefaction observed in SCD was more pronounced in women than in men (interaction: P < .01). Muscle hypoxia markers were not different between groups. Compared with CON, the surface area for 100 myocytes was lower in men with SCD (both P < .001) but not in women. Advanced oxidation protein products were increased in patients with SCD and to a greater extent in men (interaction: P < .02). Components of muscle pH regulation were specifically higher in SCT. Compared with UT, ET saw its microvascular network and oxidative capacities increase, without differences between men and women. Our results suggest that SCD-associated capillary rarefaction and enlargement could be related to disturbed hemodynamics and reduced erythrocytes deformability, respectively. The specific remodeling in female patients with SCD included aggravated microvascular remodeling but preserved myocytes. Muscle pH regulation mechanisms appeared specifically upregulated in carriers of SCT. Men and women with SCD improved similarly their microvasculature and muscle energetic characteristics in response to ET.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4661-4672"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559213","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":"National Alliance of Sickle Cell Centers consensus standards for transition to adult care in sickle cell disease.","authors":"Stephanie Howe Guarino, Akshat Jain, Mohan Madisetti, Kenneth Rivlin, Payal C Desai, Julie Kanter, Sophie Lanzkron, Deepa Manwani","doi":"10.1182/bloodadvances.2025015909","DOIUrl":"10.1182/bloodadvances.2025015909","url":null,"abstract":"<p><strong>Abstract: </strong>Sickle cell disease (SCD), an autosomal recessive hemoglobinopathy, affects ∼100 000 people in the United States.1 The process of transitioning from pediatric to adult SCD health care systems can be disjointed and poorly coordinated, contributing to the high morbidity and mortality seen in this population. There is no universally accepted definition of a successful SCD care transition, nor are there existing standards and recommendations for SCD clinicians. National Alliance of Sickle Cell Centers (NASCC) uses a described modified Delphi process to reach consensus among its members, through which we defined standards and recommendations for transitioning care from pediatric to adult care health systems, including the definition of successful transfer and integration into adult care, as well as the essential health data elements needed for a standardized electronic health record transition note to facilitate clinician communication. NASCC members from pediatric, adult, and life span SCD centers evaluated standards and recommendations for successful transfer and integration of care, as well as pediatric and adult transition program operating practices. Consensus was achieved for 4 standards and 14 recommendations for transition from pediatric to adult care in SCD in the areas of transition policies, documents, tracking, definitions of successful transfer and transition of care, and initial visit responsibilities. This initiative defines 2 key elements of successful transition, which will allow for the study of interventions to improve outcomes. Importantly, these materials now provide the needed framework and quantifiable metrics for clinicians to evaluate their transition programs for quality improvement.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4585-4591"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233241","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":"Inequalities in CAR T-cell therapy access for US patients with relapsed/refractory DLBCL: a SEER-Medicare data analysis.","authors":"Andrea P Chung, Jason T Shafrin, Sachin Vadgama, Kristen Hurley, Miguel-Angel Perales, Leonard C Alsfeld, Sanjana Muthukrishnan, Anik R Patel, Gunjan L Shah, Richard T Maziarz","doi":"10.1182/bloodadvances.2024015634","DOIUrl":"10.1182/bloodadvances.2024015634","url":null,"abstract":"<p><strong>Abstract: </strong>Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy has shown curative potential for patients with diffuse large B-cell lymphoma (DLBCL) and other malignancies, but its accessibility among Medicare patients, particularly in disadvantaged populations, remains uncertain. This study aims to assess CAR-T use among Medicare patients with DLBCL receiving third-line or later (3L+) treatment, focusing on access disparities and their impact on clinical outcomes. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2007 to 2020, multivariate logistic regression was used to evaluate patient characteristics and the effects of distance to authorized treatment centers (ATCs) on CAR-T access. Between 2017 and 2020, 2241 patients were treated for 3L+ DLBCL in the SEER-Medicare data, of whom 122 (5.4%) received CAR-Ts. CAR-T recipients were less likely to have multiple comorbidities (odds ratio [OR], 0.904; P = .001) but more likely to live in higher income areas (OR, 1.176; P = .004). If distance to the nearest ATC for \"poor-access\" states (average distance to ATC, 104.4 miles) decreased to the average distance in \"better-access\" states (34.2 miles), there would be a 37.6% increase in number of patients receiving CAR-Ts (6.6%-9.1%; P < .001). These findings highlight substantial disparities in CAR-T use, driven by geographic and socioeconomic factors. Addressing these barriers could significantly enhance equitable access to CAR-T therapy and improve outcomes for underserved populations, emphasizing the need for targeted interventions to reduce geographic and systemic barriers to care.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4727-4735"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076050","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":"Sequential BCMA CAR T-cell therapy in refractory multiple myeloma.","authors":"Tim Richardson, Udo Holtick, Jan-Hendrik Frenking, Hishan Tharmaseelan, Hyatt Balke-Want, Ruth Flümann, Elias Karl Mai, Sandra Sauer, Raphael Teipel, Malte von Bonin, Michael Hallek, Christof Scheid, Philipp Gödel","doi":"10.1182/bloodadvances.2025016712","DOIUrl":"10.1182/bloodadvances.2025016712","url":null,"abstract":"<p><strong>Abstract: </strong>Multiple myeloma (MM) relapsing after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell treatment remains a therapeutic challenge. Data on re-exposure to CAR T-cell therapy targeting the same antigen are scarce. We analyzed 10 heavily pretreated patients with RRMM at 3 medical centers treated with the commercially approved CAR T-cell therapy product idecabtagene vicleucel in a real-world setting. Upon relapse, all patients received ciltacabtagene autoleucel as a second CAR T-cell therapy infusion, with bridging treatments permitted between both therapies. Sequential therapy with BCMA-directed CAR T-cell therapy was safe, with no higher-grade immune-cell-associated side effects or new safety signals. We found robust CAR T-cell therapy expansion and high response rates (100% with at least very good partial response, with 60% achieving minimal residual disease negativity), with an estimated progression-free survival of 64.8% (95% confidence interval, 39%-100%) at 6 months after the second CAR T-cell treatment. Duration of response to first CAR T-cell therapy was predictive for durable responses to the second CAR T-cell therapy product. Loss of BCMA antigen occurred in only 1 of 3 patients relapsing after ciltacabtagene autoleucel. Two of three relapsing patients died within a year, and showed no further response to bispecific antibody treatment. To our knowledge, this study provides the first real-world evidence that sequential treatment with 2 different commercially approved BCMA CAR T-cell therapy products is both feasible and effective, particularly in patients with prolonged responses to initial BCMA CAR T-cell therapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4624-4630"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612106","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":"Safety and efficacy of apixaban thrombosis prevention in pediatric patients with obesity and acute lymphoblastic leukemia.","authors":"Vilmarie Rodriguez, Sarah H O'Brien, Etan Orgel, Corinna L Schultz, Adam J Esbenshade, Arteid Memaj, Joshua L Dyme, Nicholas A Favatella, Lesley G Mitchell","doi":"10.1182/bloodadvances.2025016160","DOIUrl":"10.1182/bloodadvances.2025016160","url":null,"abstract":"<p><strong>Abstract: </strong>Pediatric patients with acute lymphoblastic leukemia and lymphoma (ALL/LL) and obesity are at increased risk for venous thromboembolism (VTE). The PREVAPIX-ALL trial was an open-label, randomized, controlled trial assessing the safety and efficacy of apixaban for VTE prevention in pediatric patients with ALL/LL. An a priori subgroup analysis of patients with obesity in the PREVAPIX-ALL trial was planned because of increased VTE risk in this group. Patients with obesity, aged ≥2 to <18 years, central venous catheter, and chemotherapy containing asparaginase were randomized to apixaban (prophylactic dose) vs standard of care (SOC; no anticoagulation) during induction chemotherapy. The primary efficacy end point was a composite of nonfatal symptomatic and asymptomatic VTE and VTE-related death. The primary and secondary safety outcomes were major bleeding and a composite of major and clinically relevant nonmajor (CRNM) bleeding, respectively. A total of 82 PREVAPIX-ALL participants presented with obesity, of whom 42 were randomized to apixaban. For the primary efficacy end point, a significant decrease in VTE events was present in the apixaban arm (1/42 [2.4%]) as compared with the SOC arm (10/40 [25%]; relative risk [RR], 0.09; 95% confidence interval [CI], 0.01-0.97; P = .007). There was a statistically significant treatment obesity interaction, P = .03. No statistically significant difference was observed for the primary efficacy end point among the nonobese group (RR, 0.85; 95% CI, 0.53-1.37; P = .50). No statistically significant difference in major or CRNM bleeding was observed. Apixaban prophylaxis in patients with obesity and ALL/LL resulted in a statistically significant VTE risk reduction with no increase bleeding. This trial was registered at www.clinicaltrials.gov as #NCT02369653.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4738-4747"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282410","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":"Long-term outcomes of genome-edited \"universal\" CAR19 T cells for relapsed/refractory B-ALL at a single pediatric center.","authors":"Daniela Guardo, Avijeet Kumar Mishra, Hebatalla Rashed, Kimberly Gilmour, Stuart Adams, Danielle Pinner, Martin Sauer, Ajay Vora, Paul Veys, Vesna Pavasovic, Kanchan Rao, Waseem Qasim","doi":"10.1182/bloodadvances.2025016366","DOIUrl":"10.1182/bloodadvances.2025016366","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4750-4754"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552346","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":"Age-adjusted dosing of fludarabine for lymphodepletion in CAR T-cell therapy: a clinical trial simulation study.","authors":"John C Panetta, Aimee C Talleur, Swati Naik, Stephen Gottschalk, Markos Leggas","doi":"10.1182/bloodadvances.2025015928","DOIUrl":"10.1182/bloodadvances.2025015928","url":null,"abstract":"<p><strong>Abstract: </strong>Fludarabine (FLU) is used for lymphodepletion and improves the persistence and expansion of chimeric antigen receptor (CAR) T cells in vivo. Higher FLU systemic exposure is associated with lower relapse risk and improved leukemia-free survival in pediatric patients with acute lymphoblastic leukemia treated with CD19 CAR T-cell therapy. FLU pharmacokinetics (PKs) is age dependent, with increased clearance in younger children. Here, we used modeling and simulation, including clinical trial simulations, to define age-adjusted FLU dosage regimens that may maintain effective FLU exposures and improve outcomes. The FLU PK and pharmacodynamic relationships with overall survival (OS) and cumulative incidence of relapse (CIR) were derived from published pediatric populations. Four FLU dosages were considered for the simulations: 75 or 120 mg/m2 cumulative fixed dose, age-adjusted dosing, and doses based on therapeutic drug monitoring (TDM). The target FLU cumulative area under the curve range was defined as 13.8 to 25 mg × h/L. Clinical trial simulations showed that across the pediatric age range, the number of individuals in the target range increased from a median of 22% to 61% with fixed dosages, to 72% with age-adjusted dosing and 94% with TDM. Clinical trial simulations also showed that age-adjusted or TDM dosing could increase the median number of individuals with OS at 24 months by 67% and decrease the median number of individuals with CIR at 12 months by 72%, compared with fixed dosages. In conclusion, these simulation studies support using FLU age-adjusted or TDM dosing to increase the number of individuals achieving exposure within the targeted range and, therefore, improve clinical outcomes.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4676-4682"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559208","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":"Asciminib for relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.","authors":"Mathilde Chanut, Aurélie Cabannes-Hamy, Marie Balsat, Nassim Sahki, Emmanuel Raffoux, Yosr Hicheri, Bruno Lioure, Lucie Laemmel, Thibaut Leguay, Victoria Cacheux, Maria Pilar Gallego-Hernanz, Andrea Pieragostini, Gabrielle Roth-Guepin, Ludovic Gabellier, Nathalie Denizon, Lise Willems, Quentin Cabrera, Sylvain Chantepie, Valérie Coiteux, Claudie Capdupuy, Martin Carré, Antoine Machet, Juliette Lambert, Sandrine Roux, Franck-Emmanuel Nicolini, Nicolas Boissel, Emmanuelle Clappier, Rathana Kim, Philippe Rousselot","doi":"10.1182/bloodadvances.2025016665","DOIUrl":"10.1182/bloodadvances.2025016665","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4580-4584"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552344","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":"PROM1/CD133 marks a proliferative stem cell-like population of blasts in KMT2A rearranged infant ALL.","authors":"Joe Wilson Cross, Lucy Field, Alastair Smith, Emily Neil, Lucy Hamer, Thomas Jackson, Natalina Elliott, Siobhan Rice, Nicholas Crump, Joe Harman, Rebecca E Ling, Qingqing Wu, Nouhad El Ouazzani, Rebecca Thomas, Sarah Inglott, Jack Bartram, Owen Smith, Jonathan Bond, Irene Roberts, Thomas A Milne, Anindita Roy","doi":"10.1182/bloodadvances.2024015185","DOIUrl":"10.1182/bloodadvances.2024015185","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4607-4613"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559212","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":"Estimation of benefit to bispecific antibodies in US patients with lymphoma and multiple myeloma.","authors":"Fausto Alfredo Rios-Olais, Talal Hilal","doi":"10.1182/bloodadvances.2025016176","DOIUrl":"10.1182/bloodadvances.2025016176","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4673-4675"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648536","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}