Prospective study of thromboembolism in 1038 children with acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology (NOPHO) study. (30th January 2016)

• Record Type: Journal Article
• Authors: Tuckuviene, R.; Ranta, S.; Albertsen, B. K.; Andersson, N. G.; Bendtsen, M. D.; Frisk, T.; Gunnes, M. W.; Helgestad, J.; Heyman, M. M.; Jonsson, O. G.; Mäkipernaa, A.; Pruunsild, K.; Tedgård, U.; Trakymiene, S. S.; Ruud, E.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 14:Number 3(2016:Mar.)
• Page Start: 485
• Page End: 494
• Publication Date: 2016-01-30
• Subjects: acute lymphoblastic leukemia -- asparaginase -- children -- thromboembolism; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13236
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : Essentials Children with acute lymphoblastic leukemia (ALL) are at risk of thromboembolism (TE). This is a prospective evaluation of the incidence, risk factors and outcomes of TE in 1038 children with ALL. TE occurred in 6.1% of children, with the highest incidence (20.5%) among those aged 15–17 years. A TE‐associated case fatality of 6.4% indicates that TE is a severe complication of ALL treatment. Summary: Background: Thromboembolism (TE) is a major toxicity in children with acute lymphoblastic leukemia (ALL) and may have a negative impact on ALL treatment. Objectives: To examine the cumulative incidence, outcomes and risk factors associated with TE in children with leukemia. Patients/Methods: We prospectively evaluated TE in 1038 Nordic children and adolescents (≥ 1 and < 18 years) diagnosed with ALL during 2008–2013 and treated according to the NOPHO (Nordic Society of Pediatric Hematology and Oncology)‐ALL 2008 protocol. The cohort was followed until December 2014. Cox proportional regression was used to compute hazard ratios (HRs). Results: TE events ( n = 63) occurred most frequently in conjunction with asparaginase (ASP) administration (52/63). The cumulative incidence of TE was 6.1% (95% confidence interval [CI], 4.8–7.7). Being aged 15–17 years was associated with an increased risk of TE (adjusted HR of 4.0; 95% CI, 2.1–7.7). We found a TE‐associated 30‐day case fatality of 6.4% (95% CI, 1.8–15.5) and TE‐related truncation of ASP therapy in 36.2% (21/58). Major hemorrhage occurred in 3.5% (2/58) of anticoagulated patients. Minor hemorrhage was reported in two out of 58 patients. No major bleeds occurred in children who received low‐molecular‐weight heparin. Conclusions: Methods to identify children and adolescents who will benefit from thromboprophylaxis during ALL treatment are called for. The truncation of ASP should be avoided. The long‐term survival outcomes for ALL patients with TE require close monitoring in the future.