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    Flt3-itd allelic burden and acute promyelocytic leukemia risk stratification

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    Author
    Li, A.Y.
    Kashanian, S.M.
    Hambley, B.C.
    Zacholski, K.
    Duong, V.H.
    Chaer, F.E.
    Holtzman, N.G.
    Gojo, I.
    Webster, J.A.
    Norsworthy, K.J.
    Smith, B.D.
    Dezern, A.E.
    Levis, M.J.
    Baer, M.R.
    Kamangar, F.
    Ghiaur, G.
    Emadi, A.
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    Date
    2021-03-21
    Journal
    Biology
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/biology10030243
    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. © 2021 by the authors.
    Sponsors
    This research was partially funded by the University of Maryland Greenebaum Comprehensive Cancer Center Support Grant, grant number P30CA134274; the NHLBI, grant numbers K08HL127269 and R03HL145226; the NCI, grant number P01CA225618; and the State of Maryland's Cigarette Restitution Funds.
    Keyword
    APL
    FLT3-ITD
    Leukemia
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15151
    ae974a485f413a2113503eed53cd6c53
    10.3390/biology10030243
    Scopus Count
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