Document Detail


Successful imatinib treatment of cardiac involvement of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia followed by severe hepatotoxicity.
MedLine Citation:
PMID:  17988989     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Case Reports; Journal Article; Review    
Journal Detail:
Title:  International journal of hematology     Volume:  86     ISSN:  0925-5710     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-11-08     Completed Date:  2007-12-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  233-7     Citation Subset:  IM    
Affiliation:
Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan. ara.hema@tmd.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adult
Antineoplastic Agents / administration & dosage,  adverse effects*
Biopsy
Chromosomes, Human, Pair 4 / genetics
Chronic Disease
Drug-Induced Liver Injury*
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
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
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/FIP1L1-PDGFRA fusion protein, human; 0/Glucocorticoids; 0/Oncogene Proteins, Fusion; 0/Piperazines; 0/Pyrimidines; 0/Sodium Potassium Chloride Symporter Inhibitors; 0/mRNA Cleavage and Polyadenylation Factors; 152459-95-5/imatinib; 50-24-8/Prednisolone; 54-31-9/Furosemide; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor alpha

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