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Endothelial dysfunction and thromboembolism in children, adolescents, and young adults with acute lymphoblastic leukemia

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Endothelial dysfunction has not previously been investigated as a thrombogenic risk factor among patients with acute lymphoblastic leukemia (ALL), known to be at high risk of thromboembolism. We retrospectively explored the association between three circulating biomarkers of endothelial dysfunction (thrombomodulin, syndecan-1, VEGFR-1) measured in prospectively collected blood samples and risk of thromboembolism in 55 cases and 165 time-matched controls, treated according to the NOPHO ALL2008 protocol. In age-, sex-, and risk group-adjusted analysis, increasing levels of thrombomodulin and VEGFR-1 were independently associated with increased odds of developing thromboembolism (OR 1.37 per 1 ng/mL [95% CI 1.20‒1.56, P < 0.0001] and OR 1.21 per 100 pg/mL [95% CI 1.02‒1.21, P = 0.005], respectively). These associations remained significant when including only samples drawn >30 days before thromboembolic diagnosis. Thrombomodulin levels were on average 3.2 ng/mL (95% CI 2.6-8.2 ng/mL) higher in samples with measurable asparaginase activity (P < 0.0001). Among single nucleotide variants located in or neighboring coding genes for the three biomarkers, none were significantly associated with odds of thromboembolism. If results are validated in another cohort, thrombomodulin and VEGFR-1 could serve as predictive biomarkers, identifying patients in need of preemptive antithrombotic prophylaxis.

Original languageEnglish
JournalLeukemia
Volume36
Issue number2
Pages (from-to)361-369
Number of pages9
ISSN0887-6924
DOIs
Publication statusPublished - Feb 2022

    Research areas

  • Adolescent, Adult, Asparaginase/metabolism, Case-Control Studies, Child, Child, Preschool, Endothelium, Vascular/physiology, Female, Follow-Up Studies, Humans, Infant, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications, Prognosis, Retrospective Studies, Risk Factors, Thromboembolism/enzymology, Young Adult

ID: 67654436