Biology (Mar 2021)

<i>FLT3</i>-ITD Allelic Burden and Acute Promyelocytic Leukemia Risk Stratification

  • Andrew Y. Li,
  • Sarah M. Kashanian,
  • Bryan C. 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

DOI
https://doi.org/10.3390/biology10030243
Journal volume & issue
Vol. 10, no. 3
p. 243

Abstract

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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 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 p 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 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 FLT3-ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.

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