RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia

Abstract

Background: RUNX1 (AML1) amplification in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poor survival for unclear reasons. Our anecdotal experience suggests that children with B-ALL and RUNX1 amplification might be predisposed to thrombosis.

Procedure: We performed a retrospective cohort study of children with B-ALL treated from 2008 to 2014 at the North Carolina Children's Hospital. Patient demographics, cytogenetics, and diagnosis of thrombosis were extracted by blinded chart review. Analysis was performed examining the relationship between RUNX1 amplification and thrombosis.

Results: We identified 119 patients with B-ALL and a median age of 4.9 years (interquartile range, 2.9 to 8.6 y) at diagnosis. Four patients (3%) had RUNX1 amplification. The average number of RUNX1 copies among those with amplification was 5 (SD 0.81 [range, 4 to 6]). Eighteen thromboses were diagnosed within 6 months of starting treatment. These events were more likely among patients with RUNX1 amplification than in patients without amplification (75% vs. 13%; RR 5.75, 95% confidence interval, 2.75-12.01).

Conclusions: RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings.