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	Ayako Arai, Weihua Yan, Shihoko Wakabayashi, Shin Hayashi, Johji Inazawa, Osamu Miura
Journal	International journal of hematology (Int J Hematol) Vol. 86 Issue 3 Pg. 233-7 (Oct 2007) ISSN: 0925-5710 [Print] Japan
PMID	17988989 (Publication Type: Case Reports, Journal Article, Review)
Chemical References	Antineoplastic Agents Benzamides Glucocorticoids Oncogene Proteins, Fusion Piperazines Pyrimidines Sodium Potassium Chloride Symporter Inhibitors mRNA Cleavage and Polyadenylation Factors Furosemide Imatinib Mesylate Prednisolone FIP1L1-PDGFRA fusion protein, human Receptor, Platelet-Derived Growth Factor alpha
Topics	Adult Antineoplastic Agents (administration & dosage, adverse effects) Benzamides Biopsy Chemical and Drug Induced Liver Injury Chromosomes, Human, Pair 4 (genetics) Chronic Disease Exons (genetics) Female Furosemide (administration & dosage) Glucocorticoids (administration & dosage) Heart Diseases (complications, drug therapy, genetics, pathology) Heart Ventricles (pathology) Hepatocytes (pathology) Humans Hypereosinophilic Syndrome (complications, drug therapy, genetics, pathology) Imatinib Mesylate Introns (genetics) Liver Diseases (drug therapy, genetics, pathology) Lymphocytes (pathology) Male Middle Aged Necrosis Oncogene Proteins, Fusion (genetics) Piperazines (administration & dosage, adverse effects) Prednisolone (administration & dosage) Pyrimidines (administration & dosage, adverse effects) Receptor, Platelet-Derived Growth Factor alpha (genetics) Sequence Deletion Sodium Potassium Chloride Symporter Inhibitors (administration & dosage) Thrombosis (complications, drug therapy, genetics, pathology) mRNA Cleavage and Polyadenylation Factors (genetics)

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