Thromboembolism in acute lymphoblastic leukemia: Results of nopho all2008 protocol treatment in patients aged 1 to 45 years

Research output: Contribution to journalArticle

Abstract

Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N 5 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P 5 .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged lymph nodes, 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P < .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P 5 .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P 5 .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P £ .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.

Details

Authors
  • Cecilie Utke Rank
  • Nina Toft
  • Ruta Tuckuviene
  • Kathrine Grell
  • Ove Juul Nielsen
  • Thomas Leth Frandsen
  • Hanne Vibeke Hansen Marquart
  • Birgitte Klug Albertsen
  • Helene Hallböök
  • Ellen Ruud
  • Kirsten Brunsvig Jarvis
  • Petter Quist-Paulsen
  • Pasi Huttunen
  • Ulla Wartiovaara-Kautto
  • Ólafur Gísli Jónsson
  • Sonata Saulyte Trakymiene
  • Laimonas Griškevičius
  • Kadri Saks
  • Mari Punab
  • Kjeld Schmiegelow
External organisations
  • University of Copenhagen
  • Aarhus University Hospital
  • Skåne University Hospital
  • Uppsala University Hospital
  • St. Olav’s University Hospital
  • Helsinki University Central Hospital
  • National University Hospital of Iceland
  • Tartu University Hospital
  • Copenhagen University Hospital
  • Aalborg University Hospital
  • Oslo university hospital
  • University of Helsinki
  • Vilnius University Hospital
  • Tallinn Children's Hospital
  • Vilnius University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)2475-2484
Number of pages10
JournalBlood
Volume131
Issue number22
Publication statusPublished - 2018 May 31
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes