PMID- 36002756 OWN - NLM STAT- MEDLINE DCOM- 20220913 LR - 20220913 IS - 1432-0584 (Electronic) IS - 0939-5555 (Linking) VI - 101 IP - 10 DP - 2022 Oct TI - Bosutinib-induced late-onset severe liver injury preceded by eosinophilia. PG - 2257-2262 LID - 10.1007/s00277-022-04945-1 [doi] AB - 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. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Watanabe, Naoki AU - Watanabe N AD - Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. FAU - Takaku, Tomoiku AU - Takaku T AUID- ORCID: 0000-0002-6493-6225 AD - Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. ttakaku@juntendo.ac.jp. FAU - Fujioka, Isao AU - Fujioka I AD - Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. FAU - Tsuchiya, Shun AU - Tsuchiya S AD - Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. FAU - Ando, Miki AU - Ando M AD - Department of Hematology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. LA - eng PT - Journal Article DEP - 20220825 PL - Germany TA - Ann Hematol JT - Annals of hematology JID - 9107334 RN - 0 (Aniline Compounds) RN - 0 (Antineoplastic Agents) RN - 0 (Nitriles) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinolines) RN - 5018V4AEZ0 (bosutinib) SB - IM MH - Aniline Compounds MH - *Antineoplastic Agents/adverse effects MH - *Eosinophilia/chemically induced MH - Humans MH - *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/chemically induced/drug therapy MH - Liver MH - Nitriles MH - Protein Kinase Inhibitors/adverse effects MH - *Quinolines/adverse effects MH - Retrospective Studies OTO - NOTNLM OT - Bosutinib OT - Chronic myeloid leukemia OT - Drug-induced liver injury OT - Eosinophilia OT - Tyrosine kinase inhibitor EDAT- 2022/08/25 06:00 MHDA- 2022/09/14 06:00 CRDT- 2022/08/24 23:31 PHST- 2022/05/06 00:00 [received] PHST- 2022/08/04 00:00 [accepted] PHST- 2022/08/25 06:00 [pubmed] PHST- 2022/09/14 06:00 [medline] PHST- 2022/08/24 23:31 [entrez] AID - 10.1007/s00277-022-04945-1 [pii] AID - 10.1007/s00277-022-04945-1 [doi] PST - ppublish SO - Ann Hematol. 2022 Oct;101(10):2257-2262. doi: 10.1007/s00277-022-04945-1. Epub 2022 Aug 25.