Blood advances最新文献

{"title":"Genetic variation at PPM1H predicts mobilization efficiency in stem cell donors.","authors":"Yen Phuong La, Daniela Torres Di Bello, Maria Laura Mahecha Escobar, Caterina Cafaro, Stina Wichert, Aitzkoa Lopez de Lapuente Portilla, Björn Nilsson","doi":"10.1182/bloodadvances.2024015246","DOIUrl":"10.1182/bloodadvances.2024015246","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4683-4686"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612100","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":"A standardized metric to define a successful transition from pediatric to adult care in sickle cell disease.","authors":"Galia Pollock, Susanna Curtis","doi":"10.1182/bloodadvances.2025017088","DOIUrl":"10.1182/bloodadvances.2025017088","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 18","pages":"4622-4623"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032797","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":"Elucidating the dynamics of integrin αIIbβ3 from native platelet membranes by cryo-EM with build-and-retrieve method.","authors":"Xu Han, Zhemin Zhang, Chih-Chia Su, Meinan Lyu, Masaru Miyagi, Edward Yu, Marvin T Nieman","doi":"10.1182/bloodadvances.2025016209","DOIUrl":"10.1182/bloodadvances.2025016209","url":null,"abstract":"<p><strong>Abstract: </strong>Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that affect the protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins to be solved from homogeneous samples. Our recent breakthroughs in data processing now make it feasible to obtain atomic-level-resolution protein structures from crude preparations in their native environments by integrating cryo-EM with the \"build-and-retrieve\" (BaR) data processing methodology. We applied this iterative bottom-up methodology on resting human platelet membranes for an in-depth systems biology approach to uncover how lipids, metal binding, post-translational modifications, and cofactor associations in the native environment regulate platelet function at the molecular level. Here, we report using cryo-EM followed by the BaR method to solve the unmodified integrin αIIbβ3 structure directly from resting human platelet membranes in its inactivated and intermediate states at 2.75 and 2.67 Å, respectively. Furthermore, we also solved a novel dimer conformation of αIIbβ3 at 2.85 Å formed by 2 intermediate states of αIIbβ3. This may indicate a previously unknown self-regulatory mechanism of αIIbβ3 in its native environment. In conclusion, our data show the power of using cryo-EM with the BaR method to determine 3 distinct structures including a novel dimer directly from natural sources. This approach allows us to identify unrecognized regulation mechanisms for proteins without artifacts owing to purification processes. These data have the potential to enrich our understanding of platelet signaling circuitry.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4592-4606"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233238","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":"Maintenance therapy with romidepsin after autologous stem-cell transplant for peripheral T-cell lymphoma.","authors":"Niloufer Khan, Parastoo B Dahi, Farhad Khimani, Andrei R Shustov, Mazyar Shadman, Jia Ruan, Alison J Moskowitz, Andrew D Zelenetz, Ariela Noy, David J Straus, Pamela Drullinsky, Audrey Hamilton, Anita Kumar, Craig S Sauter, Gunjan L Shah, Matthew J Matasar, Esther Drill, Theresa Davey, Helen Hancock, Nivetha Ganesan, Natasha Galasso, Koen van Beisen, Sergio Giralt, Steven M Horwitz","doi":"10.1182/bloodadvances.2024014263","DOIUrl":"10.1182/bloodadvances.2024014263","url":null,"abstract":"<p><strong>Abstract: </strong>Patients with peripheral T-cell lymphoma (PTCL) have suboptimal outcomes. Autologous hematopoietic stem-cell transplantation (AHCT) is a therapeutic strategy for patients in first complete remission (CR1) or first partial remission (PR1), with median intent-to-treat progression-free survival (PFS) of 36% to 48%. Romidepsin is a histone deacetylase inhibitor used for treatment of relapsed/refractory PTCL. We present a multicenter study to evaluate the PFS of patients receiving maintenance therapy with romidepsin after AHCT. Twenty-six patients who underwent AHCT in CR1 or PR1 were evaluated for the primary end point of 2-year PFS. The exploratory cohort enrolled patients who underwent transplantation during or after CR/PR2 (n = 5) or high-risk histologies (n = 2). Patients underwent AHCT with carmustine, etoposide, cytarabine, and melphalan conditioning. Romidepsin 14 mg/m2 was started on days 42 to 80 after -AHCT every other week until 6 months of -AHCT, every 3 weeks between 6 months and 1-year of -AHCT, and every 4 weeks between 1 and 2 years of -AHCT. PFS was estimated using the Kaplan-Meier analysis. Forty-seven patients consented and 13 did not receive romidepsin. With a median progression-free follow-up of 32 months (range, 24-36), 15 of the first 25 patients in cohort 1 were progression-free after 2 years. The estimated 2-year PFS was 62% (95% confidence interval, 45-83). The most common toxicities were fatigue (n = 24, 73%), decreased platelets (n = 16, 48%), and anemia (n = 16, 48%). Although the study did not meet its desired primary efficacy end point, maintenance romidepsin was feasible, with a favorable estimated 2-year PFS of 62%. This trial was registered at www.ClinicalTrials.gov as #NCT01908777.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4687-4692"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779167","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":"Immunoglobulin prophylaxis should be initiated after bispecific antibody therapy in multiple myeloma, regardless of IgG levels.","authors":"Rahul Banerjee, Meera Mohan, Kai Rejeski, Benjamin R Puliafito, Diana D Cirstea, Gurbakhash Kaur, Shonali Midha, Georgia J McCaughan, Nikhil M Kumar, Nikita Mehra, Bhausaheb Bagal, Noopur S Raje","doi":"10.1182/bloodadvances.2025016490","DOIUrl":"10.1182/bloodadvances.2025016490","url":null,"abstract":"<p><strong>Abstract: </strong>Bispecific antibodies (bsAbs), such as teclistamab, elranatamab, linvoseltamab, and talquetamab, have impressive efficacy in multiple myeloma (MM) but come with substantial infectious risks that do not dissipate over time. Immunoglobulin replacement therapy (IgRT), which includes IV and subcutaneous (SC) immunoglobulins, may lower these risks. In this viewpoint, we contrast primary IgRT prophylaxis (initiation regardless of IgG levels) with preemptive IgRT treatment (initiation only once IgG levels fall below a certain threshold) in this setting. We make evidence-based arguments for primary prophylaxis as a safer and simpler approach than preemptive IgG-guided IgRT. We also discuss strategies to improve the cost-effectiveness of IV and SC immunoglobulins across the world. Given the overwhelmingly favorable benefit-risk profile of IgRT, coupled with the limitations inherent to IgG measurements in MM, withholding IgRT access based on arbitrary IgG thresholds is neither scientifically sound nor clinically appropriate for patients with MM who are receiving bsAb therapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"4720-4726"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681974","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":"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":"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}