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

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  3. T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol

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  • Kirsten Brunsvig Jarvis
  • Marissa LeBlanc
  • Morten Tulstrup
  • Rikke Linnemann Nielsen
  • Birgitte Klug Albertsen
  • Ramneek Gupta
  • Pasi Huttunen
  • Ólafur Gisli Jónsson
  • Cecilie Utke Rank
  • Susanna Ranta
  • Ellen Ruud
  • Kadri Saks
  • Sonata Saulyte Trakymiene
  • Ruta Tuckuviene
  • Kjeld Schmiegelow
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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.

Original languageEnglish
JournalThrombosis Research
Volume184
Pages (from-to)92-98
Number of pages7
ISSN0049-3848
DOIs
Publication statusPublished - Dec 2019

ID: 58919471