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

Pediatr Blood Cancer. 2022 Sep;69(9):e29786. doi: 10.1002/pbc.29786. Epub 2022 May 20.


Background: 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).

Methods: We reviewed medical records from patients diagnosed with CML between 2006 and 2019 at <21 years of age and prescribed one or more TKIs. Patients treated with stem cell transplant were excluded. Outcomes were captured beginning at 1 year after CML diagnosis. Outcome incidence was described overall and stratified by TKI exposure during the data-capture period.

Results: Twenty-two eligible TKI-exposed patients with CML were identified. The median follow-up was 6.0 years (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.

Conclusions: 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.

Keywords: chronic myeloid leukemia; late effects of cancer treatment; tyrosine kinase inhibitor.

Publication types

  • Review

MeSH terms

  • Child
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
  • Prognosis
  • Protein Kinase Inhibitors / adverse effects


  • Protein Kinase Inhibitors