Distribution and frequency of tyrosine kinase inhibitor-associated long-term complications in children with chronic myeloid leukemia.

Abstract

Tyrosine kinase inhibitors (TKIs) improve outcomes for pediatric malignancies characterized by specific gene rearrangements and mutations; however, little is known about the long-term impact of TKI exposure. Our objective was to assess the incidence and type of late-onset TKI-related toxicities in children with chronic myeloid leukemia (CML). We reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21years of age and prescribed one or more TKIs. Patients treated with stem cell transplant were excluded. Outcomes were captured beginning at 1year after CML diagnosis. Outcome incidence was described overall and stratified by TKI exposure during the data-capture period. Twenty-two eligible TKI-exposed patients with CML were identified. The median follow-up was 6.0years (range: 2.2-14.3). All pericardial (n=3) or pleural (n=3) effusion outcomes occurred in patients treated with TKIs during the data-capture period. Other outcomes included hypertension (n=2), ectopy on electrocardiogram (n=2), and gastrointestinal bleed (n=1). All outcomes were graded as mild to moderate: some resulted in a temporary discontinuation of TKI, but none led to a change in TKI. No differences were noted in outcome incidence by type of TKI exposure. TKIs have substantially improved prognosis for subsets of childhood leukemia, but there are limited long-term data to inform exposure-based risk for late-onset complications and screening. Our results suggest that TKI-exposed survivors may be at risk for long-term outcomes that extend well into survivorship.