Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP‐C

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TE_ind ) therapy and whether TE_ind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TE_ind and whether TE_ind predicted induction failure and ALL treatment intensification. The impact of TE_ind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TE_ind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TE_ind in univariate analysis. Age and T-cell phenotype remained independent predictors of TE_ind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TE_ind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TE_ind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TE_ind was associated with age and T-cell phenotype and mortality but did not predict induction failure.