title: Successful imatinib treatment of cardiac involvement of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia followed by severe hepatotoxicity.
abstract: Imatinib is highly effective for the treatment of chronic eosinophilic leukemia (CEL) caused by the FIP1L1-PDGFRA fusion gene. However, its effectiveness for cardiac involvement of CEL has remained unclear. We describe a 46-year-old man with CEL treated with imatinib. Reverse transcriptase-polymerase chain reaction and sequencing analyses revealed a FIP1L1-PDGFRA fusion transcript with FIP1L1 intron 10 fused to PDGFRA exon 12, and fluorescent in situ hybridization analysis confirmed the interstitial deletion in chromosome 4q12. On admission, the patient had left heart failure accompanied by a large thrombus in the left ventricle. After pretreatment with furosemide and prednisolone, we started imatinib treatment at 100 mg/day. Eosinophilia disappeared within 1 week, and the left ventricular thrombus was resolved within 5 months. At 6 months after starting imatinib, the patient showed grade 4 liver dysfunction. A liver biopsy revealed hepatocyte necrosis with lymphocyte infiltration. Fortunately, the FIP1L1-PDGFRA fusion transcript had become undetectable, and imatinib treatment was stopped. The liver dysfunction resolved within a month. Although the CEL relapsed 6 months later, imatinib could be successfully resumed in combination with 25 mg/day of prednisolone. Thus, imatinib may be very effective for treating the early cardiac involvement of FIP1L1-PDGFRA-positive CEL, but it needs to be used cautiously.
authors.affiliation: Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan. ara.hema@tmd.ac.jp
authors.forename: Ayako
authors.initials: A
authors.lastname: Arai
authors.forename: Weihua
authors.initials: W
authors.lastname: Yan
authors.forename: Shihoko
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001549:Benzamides; D001706:Biopsy; D056486:Chemical and Drug Induced Liver Injury; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002908:Chronic Disease; D005091:Exons / Q000235:genetics; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D005938:Glucocorticoids / Q000008:administration & dosage; D006331:Heart Diseases / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000068877:Imatinib Mesylate; D007438:Introns / Q000235:genetics; D008107:Liver Diseases / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D011239:Prednisolone / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D017384:Sequence Deletion; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D005938:Glucocorticoids; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D039221:mRNA Cleavage and Polyadenylation Factors; D005665:Furosemide; D000068877:Imatinib Mesylate; D011239:Prednisolone; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha