{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T04:24:45Z","timestamp":1768710285889,"version":"3.49.0"},"reference-count":35,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007928","name":"Perelman School of Medicine, University of Pennsylvania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015982","name":"Midwest Athletes Against Childhood Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["HL-102035"],"award-info":[{"award-number":["HL-102035"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2023,3]]},"DOI":"10.1016\/j.jtha.2022.10.006","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T10:24:06Z","timestamp":1674642246000},"page":"488-498","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells"],"prefix":"10.1016","volume":"21","author":[{"given":"Weiqing","family":"Jing","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina K.","family":"Baumgartner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocelyn A.","family":"Schroeder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qizhen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtha.2022.10.006_bib1","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1182\/blood-2008-02-138214","article-title":"Syngeneic transplantation of hematopoietic stem cells that are genetically modified to express factor VIII in platelets restores hemostasis to hemophilia A mice with preexisting FVIII immunity","volume":"112","author":"Shi","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2022.10.006_bib2","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1111\/j.1538-7836.2012.04791.x","article-title":"Lentivirus-mediated platelet gene therapy of murine hemophilia A with pre-existing anti-factor VIII immunity","volume":"10","author":"Kuether","year":"2012","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2022.10.006_bib3","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1182\/bloodadvances.2019000516","article-title":"Nongenotoxic antibody-drug conjugate conditioning enables safe and effective platelet gene therapy of hemophilia A mice","volume":"3","author":"Gao","year":"2019","journal-title":"Blood Adv"},{"key":"10.1016\/j.jtha.2022.10.006_bib4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/bmt.2010.60","article-title":"Safety and efficacy of targeted busulfan therapy in children undergoing myeloablative matched sibling donor BMT for sickle cell disease","volume":"46","author":"McPherson","year":"2011","journal-title":"Bone Marrow Transplant"},{"key":"10.1016\/j.jtha.2022.10.006_bib5","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1177\/106002809402800911","volume":"28","author":"Buggia","year":"1994","journal-title":"Busulfan. Ann Pharmacother"},{"key":"10.1016\/j.jtha.2022.10.006_bib6","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/sj.bmt.1702042","article-title":"High-dose busulfan\/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors","volume":"24","author":"Diaz","year":"1999","journal-title":"Bone Marrow Transplant"},{"key":"10.1016\/j.jtha.2022.10.006_bib7","first-page":"437","article-title":"Busulfan-containing pre-transplant regimens for the treatment of solid tumors","volume":"14","author":"Ghalie","year":"1994","journal-title":"Bone Marrow Transplant"},{"key":"10.1016\/j.jtha.2022.10.006_bib8","first-page":"144","article-title":"The use of busulfan therapy in bone marrow transplantation. A nursing overview","volume":"12","author":"Rohaly","year":"1989","journal-title":"Cancer Nurs"},{"key":"10.1016\/j.jtha.2022.10.006_bib9","doi-asserted-by":"crossref","first-page":"6867","DOI":"10.1158\/1078-0432.CCR-11-0074","article-title":"Population pharmacokinetics of busulfan in children: increased evidence for body surface area and allometric body weight dosing of busulfan in children","volume":"17","author":"Trame","year":"2011","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jtha.2022.10.006_bib10","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.3389\/fimmu.2018.01950","article-title":"Platelet gene therapy promotes targeted peripheral tolerance by clonal deletion and induction of antigen-specific regulatory T cells","volume":"9","author":"Luo","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.jtha.2022.10.006_bib11","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.omtn.2020.12.026","article-title":"Platelet gene therapy induces robust immune tolerance even in a primed model via peripheral clonal deletion of antigen-specific T cells","volume":"23","author":"Li","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"key":"10.1016\/j.jtha.2022.10.006_bib12","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/j.1538-7836.2004.00802.x","article-title":"Pathogenic antibodies to coagulation factors. Part one: factor VIII and factor IX","volume":"2","author":"Lollar","year":"2004","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2022.10.006_bib13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1182\/blood-2003-07-2456","article-title":"Preventing restimulation of memory B cells in hemophilia A: a potential new strategy for the treatment of antibody-dependent immune disorders","volume":"104","author":"Hausl","year":"2004","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2022.10.006_bib14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/ng0595-119","article-title":"Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A","volume":"10","author":"Bi","year":"1995","journal-title":"Nat Genet"},{"key":"10.1016\/j.jtha.2022.10.006_bib15","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1172\/JCI28416","article-title":"Factor VIII ectopically targeted to platelets is therapeutic in hemophilia A with high-titer inhibitory antibodies","volume":"116","author":"Shi","year":"2006","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jtha.2022.10.006_bib16","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1182\/blood-2015-08-662916","article-title":"The immunogenicity of platelet-derived FVIII in hemophilia A mice with or without preexisting anti-FVIII immunity","volume":"127","author":"Chen","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2022.10.006_bib17","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1111\/jth.13169","article-title":"Comparison of platelet-derived and plasma factor VIII efficacy using a novel native whole blood thrombin generation assay","volume":"13","author":"Baumgartner","year":"2015","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2022.10.006_bib18","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/jth.13436","article-title":"Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice","volume":"15","author":"Baumgartner","year":"2017","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2022.10.006_bib19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/mt.2013.197","article-title":"Platelet gene therapy by lentiviral gene delivery to hematopoietic stem cells restores hemostasis and induces humoral immune tolerance in FIX(null) mice","volume":"22","author":"Chen","year":"2014","journal-title":"Mol Ther"},{"key":"10.1016\/j.jtha.2022.10.006_bib20","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1111\/jth.12633","article-title":"In\u00a0vivo enrichment of genetically manipulated platelets corrects the murine hemophilic phenotype and induces immune tolerance even using a low multiplicity of infection","volume":"12","author":"Schroeder","year":"2014","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.jtha.2022.10.006_bib21","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.4049\/jimmunol.141.11.3697","article-title":"The stem cell antigens Sca-1 and Sca-2 subdivide thymic and peripheral T lymphocytes into unique subsets","volume":"141","author":"Spangrude","year":"1988","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.jtha.2022.10.006_bib22","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/350423a0","article-title":"A\u00a0B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene","volume":"350","author":"Kitamura","year":"1991","journal-title":"Nature"},{"key":"10.1016\/j.jtha.2022.10.006_bib23","doi-asserted-by":"crossref","first-page":"5558","DOI":"10.4049\/jimmunol.165.10.5558","article-title":"A\u00a0critical role for B cells in the development of memory CD4 cells","volume":"165","author":"Linton","year":"2000","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.jtha.2022.10.006_bib24","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.4049\/jimmunol.165.8.4353","article-title":"Unexpected autoantibody production in membrane Ig-mu-deficient\/lpr mice","volume":"165","author":"Melamed","year":"2000","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.jtha.2022.10.006_bib25","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1055\/s-2004-825635","article-title":"Immune implications of gene therapy for hemophilia","volume":"30","author":"Herzog","year":"2004","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.jtha.2022.10.006_bib26","doi-asserted-by":"crossref","first-page":"4482","DOI":"10.1182\/blood-2012-05-423210","article-title":"The gene therapy journey for hemophilia: are we there yet?","volume":"120","author":"High","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2022.10.006_bib27","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-2141.2011.08925.x","article-title":"Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation","volume":"156","author":"Scott","year":"2012","journal-title":"Br J Haematol"},{"key":"10.1016\/j.jtha.2022.10.006_bib28","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1056\/NEJM198312013092202","article-title":"Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide","volume":"309","author":"Santos","year":"1983","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jtha.2022.10.006_bib29","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0140-6736(53)90884-8","article-title":"Myleran in chronic myeloid leukaemia; chemical constitution and biological action","volume":"264","author":"Haddow","year":"1953","journal-title":"Lancet"},{"key":"10.1016\/j.jtha.2022.10.006_bib30","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1365-2141.1958.tb06038.x","article-title":"The action of chlorambucil (CB. 1348) and busulphan (myleran) on the haemopoietic organs of the rat","volume":"4","author":"Elson","year":"1958","journal-title":"Br J Haematol"},{"key":"10.1016\/j.jtha.2022.10.006_bib31","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.exphem.2005.10.010","article-title":"Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model","volume":"34","author":"Kang","year":"2006","journal-title":"Exp Hematol"},{"key":"10.1016\/j.jtha.2022.10.006_bib32","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1053\/j.seminhematol.2010.03.005","article-title":"Platelet formation","volume":"47","author":"Thon","year":"2010","journal-title":"Semin Hematol"},{"key":"10.1016\/j.jtha.2022.10.006_bib33","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1182\/blood.V68.3.762.762","article-title":"Expression of antigens of the platelet glycoprotein IIb\/IIIa complex on human hematopoietic stem cells","volume":"68","author":"Fraser","year":"1986","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2022.10.006_bib34","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1182\/blood.V93.9.2898.409k17_2898_2906","article-title":"Glycoprotein IIb-IIIa is expressed on avian multilineage hematopoietic progenitor cells","volume":"93","author":"Ody","year":"1999","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2022.10.006_bib35","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1182\/blood-2008-12-193888","article-title":"Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells","volume":"114","author":"McKinney-Freeman","year":"2009","journal-title":"Blood"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783622071756?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783622071756?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T03:38:23Z","timestamp":1761536303000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783622071756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["S1538783622071756"],"URL":"https:\/\/doi.org\/10.1016\/j.jtha.2022.10.006","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtha.2022.10.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}