Background Venous thromboembolism ( VTE ) is relatively common in children with acute lymphoblastic leukemia ( ALL ). Thrombotic risk factors in ALL are asparaginase and steroids. However, within the ALL populations treated on the same regimen, it is less clear which other risk factors play a role. Furthermore, few data are available on the effect of VTE on ALL outcomes. Methods In 778 children (1‐18 years) with newly diagnosed precursor‐B‐lineage or T‐lineage ALL , treated in the Dutch Childhood Oncology Group ( DCOG ) ALL ‐10 protocol in the Netherlands (October 2004 to April 2013), we conducted a nested case control study with 59 VTE cases and 118 controls to identify risk factors for VTE . Results Fifty‐nine of 778 ALL patients developed VTE (7.6%), with cerebral venous sinus thrombosis ( CVST ) in 26 of 59 patients (44.1%). VTE occurred during induction treatment in 59.3% (n = 35) and in 40.7% (n = 24) during medium risk intensification. Conditional multivariable logistic regression analysis showed that age and ALL subtype were significantly associated with VTE (age ≥7 years: OR 2.72, 95% CI 1.33‐5.57; ALL subtype T‐ ALL : OR 2.95, 95% CI 1.02‐8.57). A multivariable Cox model showed no association between the occurrence of VTE and event free survival. In CVST patients, permanent disability was present in 34.6%. Conclusion Within this large pediatric ALL cohort, we demonstrated a high morbidity in CVST patients. Age ≥7 years at diagnosis and T‐ ALL subtype were the main risk factors for VTE , and should be considered in preventive strategies.

The etiology of pediatric venous thromboembolic disease (VTE) is multifactorial, and in most children, 1 or more clinical risk factors are present. In addition, inherited thrombophilic disorders contribute to the development of pediatric VTE. In this review, the role of inherited thrombophilic disorders in the development of pediatric VTE, as well as the benefits and limitations of thrombophilia testing, will be discussed.

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