title: Severe hepatitis and complete molecular response caused by imatinib mesylate: possible association of its serum concentration with clinical outcomes.
abstract: A 40-year-old female with chronic myelogeneous leukemia (CML) in the chronic phase was treated with imatinib mesylate (STI571) because of interferon resistance. She achieved complete cytogenetic response but not complete molecular response 3 months after STI571 administration. Six months later, she developed severe liver damage without evidence of actively infectious hepatitis A, B, C, G, E, TT virus, Epstein-Barr virus or cytomegalovirus. A significant serum level of STI571 (107 ng/ml) was detected, although she had not taken the drug for 6 days. Liver biopsy demonstrated massive hepatic necrosis, consistent with drug-induced hepatitis. She achieved complete molecular response, although she did not take STI571 for 47 days after the development of hepatitis. These results suggest that both hepatitis and molecular response were associated with the serum STI571 concentration.
authors.affiliation: Division of Hematology, Department of Medicine, Jichi Medical School, Minamikawachi, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Muroi
authors.forename: Satoko
authors.initials: S
authors.lastname: Takahashi
authors.forename: Chizuru
authors.initials: C
authors.lastname: Kawano-Yamamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takatoku
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazato
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagai
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D001706:Biopsy; D005260:Female; D006505:Hepatitis / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D008099:Liver / Q000293:injuries / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011517:Prothrombin Time; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D012621:Seasons; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate