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dc.contributor.authorHøjfeldt, Sofie G
dc.contributor.authorWolthers, Benjamin O
dc.contributor.authorTulstrup, Morten
dc.contributor.authorAbrahamsson, Jonas
dc.contributor.authorGupta, Ramneek
dc.contributor.authorHarila-Saari, Arja
dc.contributor.authorHeyman, Mats
dc.contributor.authorHenriksen, Louise T
dc.contributor.authorJónsson, Òlafur G
dc.contributor.authorLähteenmäki, Päivi M
dc.contributor.authorLund, Bendik
dc.contributor.authorPruunsild, Kaie
dc.contributor.authorVaitkeviciene, Goda
dc.contributor.authorSchmiegelow, Kjeld
dc.contributor.authorAlbertsen, Birgitte K
dc.date.accessioned2019-04-12T09:37:42Z
dc.date.available2019-04-12T09:37:42Z
dc.date.issued2019-02-01
dc.date.submitted2019-04
dc.identifier.citationGenetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008. 2019, 184(3):405-417 Br J Haematolen_US
dc.identifier.issn1365-2141
dc.identifier.pmid30450575
dc.identifier.doi10.1111/bjh.15660
dc.identifier.urihttp://hdl.handle.net/2336/620868
dc.descriptionTo access publisher's full text version of this article click on the hyperlink belowen_US
dc.description.abstractAsparaginase is essential in childhood acute lymphoblastic leukaemia (ALL) treatment, however hypersensitivity reactions to pegylated asparaginase (PEG-asparaginase) hampers anti-neoplastic efficacy. Patients with PEG-asparaginase hypersensitivity have been shown to possess zero asparaginase enzyme activity. Using this measurement to define the phenotype, we investigated genetic predisposition to PEG-asparaginase hypersensitivity in a genome-wide association study (GWAS). From July 2008 to March 2016, 1494 children were treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol. Cases were defined by clinical hypersensitivity and no enzyme activity, controls had enzyme activity ≥ 100 iu/l and no hypersensitivity symptoms. PEG-asparaginase hypersensitivity was reported in 13·8% (206/1494) of patients. Fifty-nine cases and 772 controls fulfilled GWAS inclusion criteria. The CNOT3 variant rs73062673 on 19q13.42, was associated with PEG-asparaginase allergy (P = 4·68 × 10en_US
dc.description.sponsorshipDanish Childhood Cancer Foundationen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/full/10.1111/bjh.15660en_US
dc.subjectPEG-asparaginaseen_US
dc.subjectgenome-wide association studyen_US
dc.subjecthypersensitivityen_US
dc.subjectpaediatric acute lymphoblastic leukaemiaen_US
dc.subjectBráðahvítblæðien_US
dc.subjectLyfjameðferðen_US
dc.subjectLyfen_US
dc.subjectOfnæmien_US
dc.subject.meshAsparaginaseen_US
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphomaen_US
dc.subject.meshHypersensitivityen_US
dc.titleGenetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008.en_US
dc.typeArticleen_US
dc.contributor.department1 Child and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark. 2 Department of Paediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark. 3 Department of Paediatrics, Institution for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 4 Department of Bio- and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark. 5 Department of Women's and Children's health, Uppsala University, Uppsala, Sweden. 6 Department of Women's and Children's health, Childhood Cancer Research Unit, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden. 7 Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 8 Department of Paediatric and Adolescent Medicine, Turku University Hospital and Turku University, Turku, Finland. 9 Department of Paediatrics, St. Olavs Hospital, Trondheim, Norway. 10 Department of Oncology and Haematology, University Children's Hospital, Tallinn, Estonia. 11 Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.en_US
dc.identifier.journalBritish journal of haematologyen_US
dc.rights.accessNational Consortium - Landsaðganguren_US
dc.departmentcodePED12
dc.source.journaltitleBritish journal of haematology


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