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

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 (HR).

RESULTS: TE events (n = 63) occurred most frequently in conjunction with asparaginase administration (52/63). The cumulative incidence of TE was 6.1% (95% confidence interval [CI] 4.8-7.7). Age 15 to 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 asparaginase therapy in 36.2% (21/58). Major hemorrhage occurred in 3.5% (2/58) 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 asparaginase should be avoided. The long-term survival outcomes for ALL-patients with TE require closely monitored in the future. This article is protected by copyright. All rights reserved.