Candidate single nucleotide polymorphisms and thromboembolism in acute lymphoblastic leukemia - A NOPHO ALL2008 study.

Autor: Jarvis KB; Department of Pediatric Hematology and Oncology, Oslo University Hospital, Postboks 4950, Nydalen, 0424 Oslo, Norway; Department of Pediatric Research, Oslo University Hospital, Postbok 4950, Nydalen, 0424 Oslo, Norway; The Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Postboks 1072, Blindern, 0316 Oslo, Norway. Electronic address: kirjar@ous-hf.no., LeBlanc M; Oslo Center for Biostatistics and Epidemiology, Oslo University Hospital, Postboks 4950, Nydalen, 0424 Oslo, Norway., Tulstrup M; Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University Hospital of Copenhagen, Belgdamsvej 9, 2100 Copenhagen, Denmark., Nielsen RL; Department of Health technology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark; Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, 380 Huaibeizhuang, Huairou district, Beijing, China., Albertsen BK; Children and Adolescent Health, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark., Gupta R; Department of Health technology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark., Huttunen P; Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, New Children's Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00290 Helsinki, Finland., Jónsson ÓG; Children's Hospital, Barnaspitali Hringsins, Landspitali University Hospital, Hringbraut 101, 101 Reykjavik, Iceland., Rank CU; Department of hematology, Rigshospitalet, University Hospital of Copenhagen, Belgdamsvej 9, 2100 Copenhagen, Denmark; Pediatric Oncology Research Laboratory, Rigshospitalet, University of Copenhagen, Belgdamsvej 9, 2100 Copenhagen, Denmark., Ranta S; Department of Women's and Children's Health, Karolinska University Hospital, Eugeniavägen 3, 171 76 Solna, Sweden; Childhood Cancer Research Unit, Women's and Children's Health, Karolinska Insitutet, Solnavägen 1, 171 77 Solna, Sweden., Ruud E; Department of Pediatric Hematology and Oncology, Oslo University Hospital, Postboks 4950, Nydalen, 0424 Oslo, Norway; Department of Pediatric Research, Oslo University Hospital, Postbok 4950, Nydalen, 0424 Oslo, Norway; The Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Postboks 1072, Blindern, 0316 Oslo, Norway., Saks K; Department of Hematology and Oncology, Tallinn Children's Hospital, 13419 Tallinn, Estonia., Trakymiene SS; Center for Pediatric Oncology and Hematology, Children's Hospital, Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius 08410, Lithuania., Tuckuviene R; Department of Pediatrics, Aalborg University Hospital, Hobrovej 18-22, 9100 Aalborg, Denmark., Schmiegelow K; Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University Hospital of Copenhagen, Belgdamsvej 9, 2100 Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Nørregade 10, 1165 Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Thrombosis research [Thromb Res] 2019 Dec; Vol. 184, pp. 92-98. Date of Electronic Publication: 2019 Nov 07.
DOI: 10.1016/j.thromres.2019.11.002
Abstrakt: Introduction: Thromboembolism is a serious toxicity of acute lymphoblastic leukemia treatment, and contributes to substantial morbidity and mortality. Several single nucleotide polymorphisms have been associated with thromboembolism in the general population; however, their impact in patients with acute lymphoblastic leukemia, particularly in children, remains uncertain.
Materials and Methods: We collected constitutional DNA and prospectively registered thromboembolic events in 1252 patients, 1-45 years, with acute lymphoblastic leukemia included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol in the Nordic and Baltic countries (7/2008-7/2016). Based on previously published data and a priori power calculations, we selected four single nucleotide polymorphisms: F5 rs6025, F11 rs2036914, FGG rs2066865, and ABO rs8176719.
Results: The 2.5 year cumulative incidence of thromboembolism was 7.1% (95% confidence interval (CI) 5.6-8.5). F11 rs2036914 was associated with thromboembolism (hazard ratio (HR) 1.52, 95%CI 1.11-2.07) and there was a borderline significant association for FGG rs2066865 (HR 1.37, 95%CI 0.99-1.91), but no association for ABO rs8176719 or F5 rs6025 in multiple cox regression. A genetic risk score based on F11 rs2036914 and FGG rs2066865 was associated with thromboembolism (HR 1.45 per risk allele, 95%CI 1.15-1.81), the association was strongest in adolescents 10.0-17.9 years (HR 1.64).
Conclusion: If validated, a F11 rs2036914/FGG rs2066865 risk prediction model should be tested as a stratification tool for prevention of thromboembolism in patients with acute lymphoblastic leukemia.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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