Format

Send to

Choose Destination
Thromb Res. 2019 Dec;184:92-98. doi: 10.1016/j.thromres.2019.11.002. Epub 2019 Nov 7.

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

Author information

1
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.
2
Oslo Center for Biostatistics and Epidemiology, Oslo University Hospital, Postboks 4950, Nydalen, 0424 Oslo, Norway.
3
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University Hospital of Copenhagen, Belgdamsvej 9, 2100 Copenhagen, Denmark.
4
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.
5
Children and Adolescent Health, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus, Denmark.
6
Department of Health technology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark.
7
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, New Children's Hospital, Helsinki University Hospital, Stenbäckinkatu 9, 00290 Helsinki, Finland.
8
Children's Hospital, Barnaspitali Hringsins, Landspitali University Hospital, Hringbraut 101, 101 Reykjavik, Iceland.
9
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.
10
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.
11
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.
12
Department of Hematology and Oncology, Tallinn Children's Hospital, 13419 Tallinn, Estonia.
13
Center for Pediatric Oncology and Hematology, Children's Hospital, Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius 08410, Lithuania.
14
Department of Pediatrics, Aalborg University Hospital, Hobrovej 18-22, 9100 Aalborg, Denmark.
15
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.

Abstract

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.

KEYWORDS:

Acute lymphoblastic leukemia; Single nucleotide polymorphisms; Thromboembolism

Supplemental Content

Full text links

Icon for Elsevier Science Icon for Norwegian BIBSYS system
Loading ...
Support Center