Venous Thromboembolism and Its Risk Factors in Children with Acute Lymphoblastic Leukemia in Israel: A Population-Based Study

SIMPLE SUMMARY: Current cure rates of childhood acute lymphoblastic leukemia (ALL) surpass 90% and thus the mitigation of chemotherapy-associated toxicity has become a major goal. Venous thromboembolism (VTE) is a major toxicity of ALL therapy, but its precise prevalence, risk factors, and optimal prophylaxis are yet to be determined. This study evaluated VTE in a cohort of 1191 children, including its rate, risk factors, and long-term sequelae. VTE was found in 7.5% of the cohort, 27% severe events. Most events resolved without late sequelae. We identified four risk factors associated with VTEs: Age >10 years, high-risk ALL group, severe hypertriglyceridemia during therapy, and inherited thrombophilia. Since children with these risk factors had significantly higher rates of severe VTE, a routine evaluation may identify potential candidates for prophylactic interventions. ABSTRACT: Venous thromboembolism (VTE) is a serious complication of acute lymphoblastic leukemia (ALL) therapy. The aim of this population-based study was to evaluate the rate, risk factors, and long-term sequelae of VTE in children treated for ALL. The cohort included 1191 children aged 1–19 years diagnosed with ALL between 2003–2018, prospectively enrolled in two consecutive protocols: ALL-IC BFM 2002 and AIEOP-BFM ALL 2009. VTEs occurred in 89 patients (7.5%). Long-term sequelae were uncommon. By univariate analysis, we identified four significant risk factors for VTEs: Severe hypertriglyceridemia (p = 0.005), inherited thrombophilia (p < 0.001), age >10 years (p = 0.015), and high-risk ALL group (p = 0.039). In addition, the incidence of VTE was significantly higher in patients enrolled in AIEOP-BFM ALL 2009 than in those enrolled in ALL-IC BFM 2002 (p = 0.001). Severe VTE occurred in 24 children (2%), all of whom had at least one risk factor. Elevated triglyceride levels at diagnosis did not predict hypertriglyceridemia during therapy. In a multivariate analysis of 388 children, severe hypertriglyceridemia and inherited thrombophilia were independent risk factors for VTE. Routine evaluation for these risk factors in children treated for ALL may help identify candidates for intervention.