Flt3-itd allelic burden and acute promyelocytic leukemia risk stratification

Andrew Y. Li, Sarah M. Kashanian, Bryan Hambley, Kyle Zacholski, Vu H. Duong, Firas El Chaer, Noa G. Holtzman, Ivana Gojo, Jonathan A. Webster, Kelly J. Norsworthy, Bruce Douglas Smith, Amy E. Dezern, Mark J. Levis, Maria R. Baer, Farin Kamangar, Gabriel Ghiaur, Ashkan Emadi

Research output: Contribution to journalArticlepeer-review

Abstract

The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3-ITD. APL patients with FLT3-ITD had higher baseline white blood cell counts (WBCs) (p < 0.001), higher hemoglobin, (p = 0.03), higher aspartate aminotransferase (p = 0.001), lower platelets (p = 0.004), lower fibrinogen (p = 0.003), and higher incidences of disseminated intravascular coagulation (p = 0.005), M3v variant morphology (p < 0.001), and the bcr3 isoform (p < 0.001). FLT3-ITD was associated with inferior post-consolidation complete remission (CR) (p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3-WT (wild-type) (p = 0.02). FLT3-ITD was strongly associated with baseline WBCs ≥ 25 × 109/L (odds ratio (OR): 54.4; 95% CI: 10.4–286.1; p < 0.001). High FLT3-ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increase in allelic burden corresponding to a 0.6 × 109/L increase in WBC. HR APL was associated with a 38.5% increase in allelic burden compared with low-risk (LR) APL (95% CI: 19.8–57.2; p < 0.001). Our results provide additional evidence that FLT3-ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.

Original languageEnglish (US)
Article number243
JournalBiology
Volume10
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • APL
  • FLT3-ITD
  • Leukemia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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