FLT3 -ITD Allelic Burden and Acute Promyelocytic Leukemia Risk Stratification

• Published in: Biology (Basel, Switzerland) Switzerland), 2021-03, Vol.10 (3), p.243
• Main Authors: Li, Andrew Y, Kashanian, Sarah M, Hambley, Bryan C, Zacholski, Kyle, Duong, Vu H, El Chaer, Firas, Holtzman, Noa G, Gojo, Ivana, Webster, Jonathan A, Norsworthy, Kelly J, Smith, Bruce Douglas, DeZern, Amy E, Levis, Mark J, Baer, Maria R, Kamangar, Farin, Ghiaur, Gabriel, Emadi, Ashkan
• Format: Article
• Language: English
• Subjects: APL; Communication; FLT3-ITD; leukemia
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology10030243

The significance of -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 -ITD. APL patients with -ITD had higher baseline white blood cell counts (WBCs) ( < 0.001), higher hemoglobin, ( = 0.03), higher aspartate aminotransferase ( = 0.001), lower platelets ( = 0.004), lower fibrinogen ( = 0.003), and higher incidences of disseminated intravascular coagulation ( = 0.005), M3v variant morphology ( < 0.001), and the bcr3 isoform ( < 0.001). -ITD was associated with inferior post-consolidation complete remission (CR) ( = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for -WT (wild-type) ( = 0.02). -ITD was strongly associated with baseline WBCs ≥ 25 × 10 /L (odds ratio (OR): 54.4; 95% CI: 10.4-286.1; < 0.001). High -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 × 10 /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; < 0.001). Our results provide additional evidence that -ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.