[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-409226-105":59,"doc-detail-409226-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","abatacept-today-tma-away-protecting-the-endothelium","Abatacept today, TMA away - protecting the endothelium","","Abatacept is evaluated as a dual-action strategy for children with transfusion-dependent β-thalassemia undergoing hematopoietic stem cell transplantation (HSCT). Added to standard calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis, it improves thalassemia-free survival while reducing endothelial injury syndromes including TA-TMA, SOS, and complement-associated toxicity. In a single-center retrospective study, abatacept lowered biomarkers linked to NETosis and complement activation and was well tolerated without infusion-related adverse events.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/abatacept-today-tma-away-protecting-the-endothelium/409226/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/abatacept-today-tma-away-protecting-the-endothelium/409226.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does abatacept aim to address in pediatric HSCT for transfusion-dependent β-thalassemia?","Question",{"text":113,"@type":114},"It targets transplant-associated endothelial complications, including TA-TMA and related endothelial syndromes, while also preventing acute GVHD.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was abatacept used in the study and what were the main clinical results?",{"text":118,"@type":114},"A retrospective single-center analysis compared 50 children receiving abatacept on specified post-transplant days with 14 controls; abatacept reduced acute grade 2–4 GVHD, endothelial injury syndromes, and improved thalassemia-free survival.",{"name":120,"@type":111,"acceptedAnswer":121},"What mechanism do the biomarker findings suggest for abatacept’s endothelial protective effects?",{"text":122,"@type":114},"Lower day +14 levels of circulating double-stranded DNA (a NET surrogate) and soluble C5b-9 (a complement activation marker) suggest reduced NETosis and downstream complement-driven vascular injury.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},409226,1790742806,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":24,"preview_page_count":4},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","INSIDE BLOOD ADVANCES  \nAbatacept today, TMA away: protecting the endothelium  \nAlexander Ngwube 1 and Allistair Abraham2  \n1 Division Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Cell Therapy and Bone Marrow Transplant Program, Cancer and Hematology Center, Texas Children’s Hospital, Houston, TX; and 2 Center for Cancer and Immunology Research, Cell Enhancement and Technologies for Immunotherapy, Children’s National Hospital, Washington, DC  \nComment on Khandelwal et al, page 6370  \nTransplant-associated thrombotic microangiopathy (TA-TMA) and related endothelial syndromes remain among the most vexing complications of hematopoietic stem cell transplantation (HSCT), but in this issue of Blood Advances, Khandelwal et al 1 present a good solution in the form of abatacept as a dual-action agent that not only prevents acute graft-versus-host disease (GVHD) but also reduces endothelial injury syndromes in children with transfusion-dependent β-thalassemia (TDT) who are undergoing HSCT. Their retrospective study offers compelling evidence that abatacept, when added to standard calcineurin inhibitor–based GVHD prophylaxis, improves thalassemia-free survival and mitigates transplant-related toxicities.  \nHSCT is a curative option for TDT, but transplant-related complications remain formidable.2 Decades of transfusions lead to iron overload, which catalyzes reactive oxygen species and primes the vascular endothelium for injury.3 This proinflammatory milieu, exacerbated by calcineurin inhibitors, increases susceptibility to endothelial syndromes, such as TA-TMA, sinusoidal obstruction syndrome (SOS), and posterior reversible encephalopathy syndrome.4,5 These complications, often refractory to supportive care, drive morbidity and nonrelapse mortality. Thus, strategies that simultaneously prevent GVHD and protect the endothelium are urgently needed.  \nAt the heart of this study lies a pivotal question: can abatacept, long recognized for its ability to prevent acute GVHD, also protect the vascular endothelium and thereby improve survival in children with transfusion-dependent thalassemia who are undergoing HSCT? Abatacept is a cytotoxic T lymphocyte–associated protein 4 and immunoglobin fusion protein that binds CD80/CD86, thereby blocking CD28-mediated T-cell costimulation. Its efficacy in acute GVHD prophylaxis is now well established.6 However, its potential endothelial benefits are less explored. Of note, CD80 is also expressed on neutrophils, and neutrophil extracellular traps (NETs) have been implicated in activating complement and injuring the endothelium.7 Khandelwal et al hypothesized that abatacept might blunt this immunologic cascade by reducing NET formation and downstream complement activation, thereby mitigating endothelial syndromes.  \nIn this single-center, retrospective analysis, 64 children with TDT underwent HSCT using a busulfanbased conditioning regimen. Of those, 50 received abatacept on days −1, +5, +14, and +28 after transplant, whereas 14 served as controls. The results were striking; neutrophil and platelet recovery were prompt in both groups, and infection/reactivation rates were similar, indicating that attenuating Tcell costimulation did not come at the expense of graft integrity or immune reconstitution. Acute grade  \n2 to 4 GVHD occurred in 0% of the abatacept group vs 35% of controls. Endothelial injury syndromes were significantly lower in the abatacept cohort (16% vs 64%; P = .0009) and thalassemia-free survival was 100% as opposed to 71% in the control group. Importantly, the study explored mechanistic biomarkers. The day +14 levels of circulating double-stranded DNA, a surrogate for NETs, and soluble C5b-9, a marker of complement activation, were significantly lower in the abatacept group. These findings suggest that abatacept may reduce NETosis and downstream complement activation, offering a novel explanation for its endothelial protective effects.  \nThe dual benefit, namel","cbCaitNBGoNY5HBb","https://ap.wps.com/l/cbCaitNBGoNY5HBb","pdf",174636,"English","# Transplant complications and rationale\n## Study question and mechanistic hypothesis\n## Retrospective study design and outcomes\n## Biomarkers and endothelial protection model\n## Limitations and future research directions","[{\"question\":\"What problem does abatacept aim to address in pediatric HSCT for transfusion-dependent β-thalassemia?\",\"answer\":\"It targets transplant-associated endothelial complications, including TA-TMA and related endothelial syndromes, while also preventing acute GVHD.\"},{\"question\":\"How was abatacept used in the study and what were the main clinical results?\",\"answer\":\"A retrospective single-center analysis compared 50 children receiving abatacept on specified post-transplant days with 14 controls; abatacept reduced acute grade 2–4 GVHD, endothelial injury syndromes, and improved thalassemia-free survival.\"},{\"question\":\"What mechanism do the biomarker findings suggest for abatacept’s endothelial protective effects?\",\"answer\":\"Lower day +14 levels of circulating double-stranded DNA (a NET surrogate) and soluble C5b-9 (a complement activation marker) suggest reduced NETosis and downstream complement-driven vascular injury.\"}]","Abatacept today, TMA away - protecting the endothelium | PDF",1790581702]