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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.

Venous thromboembolism in a large cohort of children with acute lymphoblastic leukemia: Risk factors and effect on prognosis