OC 38.1 - Thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: risk factors and impact on induction outcomes

Background: Thrombo-embolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness, where a pathological activation of the hemostatic system drives both TE and cancer progression.

Aims: Among children with ALL, to determine risk factors for TE during induction (TEind) and whether TEind is associated with induction failure (IF) and intensification of anti-leukemia therapy.

Methods: This retrospective cohort study using the population-based registry Cancer in Young People Canada (CYP-C) included children < 15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers. Patients were categorized as to whether they experienced TEind, defined as radiologically confirmed TE graded ≥3 as per the Common Terminology Criteria for Adverse Events v.4 within six weeks of anti-leukemic treatment start. Univariate and multivariable logistic regression models estimated predictors of TEind and predictive value of TEind on IF (progressive/refractory disease within 12 weeks of treatment start) and treatment intensification within 12 weeks of treatment start. The institutional review board approved the study; informed consent was waived.

Results: The study included 2,589 children (median age: 4.5 years, 54.6% male). Of these, 149 (5.8%) developed a TE, including 45 (1.7%) during induction (Table 1). Age ( < 1 year and ≥10 years vs. 1-9.99 years), T-cell phenotype, high-risk ALL, central nervous system and extra-medullary involvement were all associated with TEind in univariate analysis (Table 2). Age and T-cell phenotype remained independent predictors of TEind in multivariate analysis.
IF occurred in 71 patients (2.8%). No patient with TEind developed IF. Moreover, TEind was not predictive of treatment intensification (OR [95% CI]: 0.64 [0.19-1.51], p=0.238).

Conclusion(s): In this population-based study of children treated with contemporary anti-leukemia chemotherapy protocols, TEind was associated with markers of ALL aggressiveness but did not predict ALL refractoriness.