Blood advances最新文献

{"title":"BCLAF1 restrains stress responses in hematopoietic stem cells to support expansion and repopulation.","authors":"Stephanie J Crowley, Wei Yang, Lynn S White, Jun Wu, Yanan Li, Haley Schmidt, Kyunghee Choi, Jeffrey A Magee, Jeffrey J Bednarski","doi":"10.1182/bloodadvances.2024014916","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014916","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSC) rapidly expand during fetal development and after stress. Here, we identify BCLAF1 as a regulator of HSC repopulation activity with functions in expansion of fetal HSCs and hematopoietic reconstitution after stem cell transplantation. Using mice with hematopoietic-specific and inducible deletion of Bclaf1, we find that BCLAF1 promotes fetal HSC development but is dispensible for maintenance of adult HSCs at steady state. Loss of BCLAF1 in either fetal or adult HSCs significantly impairs their self-renewal and multi-lineage reconstitution activity after stem cell transplantation. Single-cell RNA sequencing of fetal hematopoietic progenitors reveals that loss of BCLAF1 reduces long-term HSCs and restrains expression of stress response genes. BCLAF1 associates with chromatin throughout the genome of fetal and adult hematopoietic cells, likely through indirect mechanisms, to regulate transcriptional programs. These results establish a novel function for the transcriptional regulator BCLAF1 in limiting stress responses in HSCs to preserve HSC development during embryogenesis and repopulation function after stem cell transplant.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172715","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":"Emergent BAX-mutated clonal hematopoiesis after venetoclax-based therapy for breast cancer.","authors":"Ing-Soo S Tiong, Tamia Nguyen, Chong Chyn Chua, Charis E Teh, Christine Muttiah, Sarah Ftouni, John F Seymour, Daniel H D Gray, Andrew W Roberts, Sarah-Jane Dawson, Geoffrey J Lindeman, Piers Blombery","doi":"10.1182/bloodadvances.2025016063","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016063","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172716","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":"Infection after CD19 chimeric antigen receptor T cell therapy for large B cell lymphoma: Real-world analysis from CIBMTR.","authors":"Kitsada Wudhikarn, Megan M Herr, Min Chen, Michael J Martens, John H Baird, Lohith Gowda, Hemalatha G Rangarajan, Muhammad Bilal Abid, Mohamed A Kharfan-Dabaja, Kristen M Williams, Siddhartha Ganguly, Jo-Anne H Young, Akshay Sharma, Giancarlo Fatobene, Tania Jain, Christopher G Kanakry, Dipenkumar Modi, Natalie S Grover, Baheyeldin Salem, Marjorie Vieira Batista, Paschalis Vergidis, Dwight E Yin, Amer M Beitinjaneh, Amar H Kelkar, Taiga Nishihori, Jennifer Holter-Chakrabarty, Usama Gergis, Melody Smith, Zeinab El Boghdadly, Christopher E Dandoy, Hemant S Murthy, Anna R Huppler, Miguel-Angel Perales, Roy F Chemaly, Joshua A Hill, Marcie Riches, Jeff J Auletta","doi":"10.1182/bloodadvances.2025016141","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016141","url":null,"abstract":"<p><p>Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 R/R LBCL patients receiving commercial CD19 CAR T-cell (n=2804 axicabtagene ciloleucel, n=546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 (24.9%) patients within 100 days post-infusion, resulting in an infection density of 0.43 per 100 patient-days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 (3.2%) patients, respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient-days. After a 24-month median follow-up, 1482 (44%) patients had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0%). Patients with Karnofsky score ≤80, infection history pre-CAR-T, axicabtagene ciloleucel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell-associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell. Furthermore, results identify patients at heightened risk for infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172129","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":"Rituximab for children with EBV-positive Burkitt lymphoma in East Africa.","authors":"William Frank Mawalla, Caroline Achola, Hadijah Nabalende, Isaac Otim, Ismail D Legason, Martin D Ogwang, Pamella M Aol, Godlove Sandi, Hadija Mwamtemi, Salama Mahawi, Elifuraha Mkwizu, Philomena G Lyamuya, Jacqueline P Kamanga, Kristin Schroeder, Paul Ntemi, Clara Chamba, Dimitris Vavoulis, Liz Morrell, Lulu Chirande, Anna Schuh","doi":"10.1182/bloodadvances.2024015234","DOIUrl":"10.1182/bloodadvances.2024015234","url":null,"abstract":"<p><strong>Abstract: </strong>The addition of rituximab to the chemotherapy backbone was shown to significantly improve outcomes of children with aggressive high-grade lymphomas in high-income countries. However, data on its safety and efficacy in children with Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) are limited. We conducted a prospective nonrandomized observational study in East African patients aged ≤25 years with confirmed BL. Patients received either the International Network for Cancer Treatment and Research (INCTR)-based standard chemotherapy (cyclophosphamide, vincristine, and methotrexate [COM]) or rituximab plus standard chemotherapy (R-COM). The primary end point was safety. The secondary outcomes were event-free and overall survival and cost-effectiveness of incorporating rituximab. Primary analyses were conducted in the intention-to-treat population. The median follow-up was 23 months. Safety analyses included 72 patients: 32 in the COM group and 40 in the R-COM group. Grade ≥3 adverse events occurred in 18% of R-COM patients and 16% of COM patients. With respect to treatment outcomes at 12 months, 5 events were observed in the R-COM group and 14 in the COM group. The 12-month event-free survival was 67% with R-COM and 43% with COM (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.24-0.98; P = .045). There were 8 deaths in the R-COM group, whereas 16 patients died in the COM group (HR, 0.32; 95% CI, 0.14-0.75; P = .009). R-COM was particularly effective in advanced-stage disease. The addition of rituximab to the INCTR-based protocol (COM) for EBV-positive BL has been observed to be safe and feasible in experienced centers in East Africa and saves lives.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"2393-2401"},"PeriodicalIF":7.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472316","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":"American Society of Hematology/International Society on Thrombosis and Haemostasis 2024 updated guidelines for treatment of venous thromboembolism in pediatric patients.","authors":"Paul Monagle, Muayad Azzam, Rachel Bercovitz, Marisol Betensky, Rukhmi Bhat, Tina Biss, Brian Branchford, Leonardo R Brandão, Anthony K C Chan, E Vincent S Faustino, Julie Jaffray, Sophie Jones, Hassan Kawtharany, Bryce A Kerlin, Nicole Kucine, Riten Kumar, Christoph Male, Marie-Claude Pelland-Marcotte, Leslie Raffini, Chittalsinh Raulji, Sarah E Sartain, Clifford M Takemoto, Cristina Tarango, C Heleen van Ommen, Maria C Velez, Sara K Vesely, John Wiernikowski, Suzan Williams, Hope P Wilson, Gary Woods, Ayesha Zia, Reem A Mustafa","doi":"10.1182/bloodadvances.2024015328","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015328","url":null,"abstract":"<p><strong>Background: </strong>The American Society of Hematology (ASH) guidelines on treatment of pediatric venous thromboembolism (VTE) were published in 2018. In the last 6 years, there has been a 10-fold increase in the number of children involved in VTE treatment trials.</p><p><strong>Objective: </strong>The ASH Committee on Quality and Guidelines agreed to update the pediatric guidelines in conjunction with the International Society on Thrombosis and Haemostasis (ISTH). These ASH/ISTH evidence-based guidelines are intended to support patients, clinicians, and other health care professionals in the management of pediatric patients with VTE.</p><p><strong>Methods: </strong>ASH/ISTH formed a multidisciplinary guideline panel to minimize potential bias from conflicts of interest. An unconflicted patient representative was not identified. The University of Kansas Health System supported the guideline development process, updating or performing systematic evidence reviews up to 2024. The panel focused specifically on the 2018 questions for which there was the greatest amount of interim data. The panel used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.</p><p><strong>Results: </strong>The panel agreed on 20 recommendations and also provided implementation guidance on the optimal use of anticoagulants in pediatric patients. Key recommendations of these guidelines include the role of DOACs in the treatment of a variety of pediatric VTEs.</p><p><strong>Conclusions: </strong>Further research is required. Key priorities are understanding the natural history of clinically unsuspected thrombosis across a range of patient subpopulations and obtaining real-world data on the use of DOACs in children.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 10","pages":"2587-2636"},"PeriodicalIF":7.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149306","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":"Phase 2 trial of cyclosporine-A, mycophenolate mofetil, and tocilizumab GVHD prophylaxis in cord blood transplantation.","authors":"Ioannis Politikos, Samantha Brown, Joshua A Fein, Stephen Eng, Kristian Casem, Stephanie Chinapen, Sean Quach, Andromachi Scaradavou, Christina Cho, Parastoo Dahi, Sergio A Giralt, Boglarka Gyurkocza, Alan M Hanash, Ann A Jakubowski, Esperanza B Papadopoulos, Miguel-Angel Perales, Doris M Ponce, Brian C Shaffer, Roni Tamari, James W Young, Sean Devlin, Jonathan U Peled, Juliet N Barker","doi":"10.1182/bloodadvances.2024014177","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014177","url":null,"abstract":"<p><strong>Abstract: </strong>Double-unit cord blood transplantation (dCBT) has been associated with high rates of progression-free survival (PFS) in adults with hematologic malignancies but also with relatively high rates of acute graft-versus-host disease (aGVHD). We conducted a single-arm, phase 2 clinical trial that investigated the addition of tocilizumab, an interleukin-6 receptor blocker, to cyclosporine-A (CSA) and mycophenolate mofetil (MMF) for aGVHD prophylaxis after intermediate-intensity dCBT. A total of 45 patients (median age, 47 years; range, 27-60 years; 80% acute leukemia; median hematopoietic cell transplant-comorbidity index, 2) were enrolled from March 2018 to March 2021. Transplant outcomes were compared with 39 previous CSA and MMF dCBT controls with similar inclusion criteria. Tocilizumab recipients had less pre-engraftment syndrome (38%; 95% confidence interval [CI], 24-52 vs 72%; 95% CI, 54-84; P < .001) but inferior day 45 neutrophil engraftment (93%; median, 25.5 days vs 97%; median, 22 days; P = .009]. The primary end point of day 100 grade 2 to 4 aGVHD was no different between groups (71%; 95% CI, 55-82 with tocilizumab vs 82%; 95% CI, 65-91; P = .11). However, there was a trend toward a lower day 100 incidence of stage 1 to 4 lower gastrointestinal aGVHD with tocilizumab (16%; 95% CI, 7-28 vs 33%; 95% CI, 19-48; P = .059). There were no significant differences in the 3-year incidences of relapse, transplant-related mortality, PFS, or overall survival between the groups. Tocilizumab recipients exhibited a distinct pattern of gut microbiome disruption. In summary, tocilizumab-based GVHD prophylaxis delayed neutrophil recovery without a significant reduction in aGVHD and had no survival benefit after dCBT. Investigation of alternative strategies to prevent severe aGVHD after dCBT is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03434730.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 10","pages":"2570-2584"},"PeriodicalIF":7.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149311","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":"Kuaban A, Croker AK, Keefer J, et al. The roadmap to integrate diversity, equity, and inclusion in hematology clinical trials: an American Society of Hematology initiative. Blood Adv. 2025;9(4):687-695.","authors":"","doi":"10.1182/bloodadvances.2025016358","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025016358","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 10","pages":"2637"},"PeriodicalIF":7.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149308","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":"Tocilizumab prophylaxis in double cord blood transplantation.","authors":"William R Drobyski","doi":"10.1182/bloodadvances.2024015785","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015785","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 10","pages":"2585-2586"},"PeriodicalIF":7.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149336","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 sequencing on PBMCs from HA & HB patients with inhibitors reveals different immune responses to FVIII & FIX.","authors":"Enhao Li, Zekun Li, Jinzeng Wang, Haoyang Wu, Yilun Xue, Can Lou, Zhenping Chen, Feng Liu, Wenman Wu, Qiulan Ding, Runhui Wu, Xuefeng Wang, Jing Dai","doi":"10.1182/bloodadvances.2025015799","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025015799","url":null,"abstract":"<p><p>Inhibitors are the most severe complication of replacement therapy in hemophilia patients. Previous studies, along with our clinical observations, have identified distinct incidence rates and clinical manifestations of factor VIII (FVIII) and factor IX (FIX) inhibitors in patients with severe hemophilia A (HA) and severe hemophilia B (HB). In order to explore different immune responses to FVIII and FIX in HA and HB patients and to elucidate the mechanisms underlying the varying clinical manifestations of these patients, we performed single-cell sequencing on peripheral blood mononuclear cells (PBMCs) collected from five HA and five HB patients with inhibitors. After quality control, a total of 75,051 cells were clustered into 19 subsets. Transcriptome analysis revealed differences in the composition of lymphocyte subsets and the functional status of immune cells between the HA and HB groups. Additionally, immune repertoire analysis indicated variations in the diversity of B and T cell clones between the two groups. HA group exhibited a relatively higher proportion of B cells and more active B cells, whereas HB group demonstrated a higher proportion of T cells, with more active CD4+ T helper (Th) cells. Our study provides insights into the distinct biological processes underlying the distinct immune responses to therapeutic FVIII and FIX in HA and HB patients, as revealed through single-cell sequencing of PBMCs from hemophilia patients with inhibitors. The data generated will serve as a valuable resource for future research on how the immune system recognizes and initiates responses to antigens with varying molecular characteristics.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118834","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":"Circulating Tumor DNA Determinants of Response and Outcome in Relapsed/Refractory Mantle Cell Lymphoma.","authors":"Leo Meriranta, Rasmus Rask Kragh Jørgensen, Annika Pasanen, Arne Kolstad, Martin Hutchings, Carsten Utoft Niemann, Tarec Christoffer El Galaly, Jon Riise, Jacob Haaber Christensen, Kristina Sonnevi, Lone Bredo Pedersen, Karin Fahl Wader, Ingrid Glimelius, Sirpa Leppä, Mats Jerkeman","doi":"10.1182/bloodadvances.2025015791","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025015791","url":null,"abstract":"<p><p>Clinical tools to guide treatment decisions in relapsed and refractory mantle cell lymphoma (R/R MCL) are limited. Moreover, the translational potential of circulating tumor DNA (ctDNA) remains largely unproven. We designed and applied panel-based duplex sequencing of ctDNA to study molecular determinants of response and outcome in 58 R/R MCL patients treated with venetoclax, lenalidomide, and rituximab. Genetic analysis revealed molecular predictors of response that were independent of clinical prognostic factors, with SMARCA4-mutated R/R MCLs responding to therapy, whereas TP53 mutations conferred resistance. Pretreatment ctDNA captured spatial heterogeneity, and its concentration was associated with multiple clinicopathological disease features and survival, independently of molecular predictors. Dynamic ctDNA assessment for minimal residual disease complemented clinical response evaluation and uncovered refractoriness in patients with molecular remission according to contemporary real-time quantitative PCR assay. Features of clonal hematopoiesis (CH) at baseline were associated with hematological toxicity during treatment and poor outcomes on follow-up. Positive selection of TP53-related CH during treatment did not compromise the specificity of ctDNA response analysis, and fragmentation signatures allowed distinction between MCL ctDNA and CH-bearing cfDNA. Taken together, we report novel features in MCL ctDNA that reveal new minimally invasive tools that could potentially transform clinical decision-making in R/R MCL.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118823","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}