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Bosutinib-induced late-onset severe liver injury preceded by eosinophilia

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Abstract

Tyrosine kinase inhibitors (TKIs) have dramatically changed the way chronic myeloid leukemia (CML) is treated. Although TKI therapy improves the overall survival of patients with CML, the management of various adverse events (AEs) from the therapy has become a major barrier to its adherence. Bosutinib is a second-generation TKI and an effective first-line treatment for CML. The most frequent AE is diarrhea; however, liver toxicity is also a major complication. In general, drug-induced hepatic enzyme elevation occurs within 1–2 weeks after treatment initiation. However, we noticed that, in a certain number of patients, liver injury appeared late (4–7 weeks) and was accompanied by eosinophilia. Herein, we retrospectively analyzed patients with CML treated with bosutinib at the Juntendo University School of Medicine and observed five patients with CML who developed late-onset liver injury with an elevation of the eosinophil count. In all cases, the liver enzyme level was within the normal range or grade 1 during the first 3 weeks of the bosutinib treatment and then elevated steeply thereafter. The pattern of hepatic toxicity was hepatocellular injury. In addition, all cases of eosinophilia tended to precede or coincide with an elevated liver enzyme level. Thus, the elevation of the eosinophil count may be a predictor for bosutinib-induced liver injury. Careful attention should be paid to delayed-onset hepatic injury, especially at 4–6 weeks after bosutinib initiation.

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Acknowledgements

The results of this study were presented in part at the 83rd Japanese Society of Hematology Annual Meeting, Japan, 2021.

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Authors and Affiliations

  1. Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Naoki Watanabe, Tomoiku Takaku, Isao Fujioka, Shun Tsuchiya & Miki Ando

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  1. Naoki Watanabe
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  2. Tomoiku Takaku
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  3. Isao Fujioka
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  4. Shun Tsuchiya
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  5. Miki Ando
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Contributions

NW, TT, and IF designed the study. TT and MA advised on the research design and analyses. NW, IF, and ST collected the patient data. NW, TT, and IF analyzed the data. NW, TT, and IF drafted the manuscript. All the authors have revised the manuscript and approved the final version of the manuscript.

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Correspondence to Tomoiku Takaku.

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Tomoiku Takaku has received a speaker honorarium from Pfizer, Inc.

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Watanabe, N., Takaku, T., Fujioka, I. et al. Bosutinib-induced late-onset severe liver injury preceded by eosinophilia. Ann Hematol 101, 2257–2262 (2022). https://doi.org/10.1007/s00277-022-04945-1

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  • DOI: https://doi.org/10.1007/s00277-022-04945-1

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