伴t（5；12）（q31；p13），FIP1L1／PDGFRα阴性慢性嗜酸细胞白血病一例并文献复习

FIP1L1/PDGFRα fusion gene-negative chronic eosinophilic leukemia with t （ 5;12 ） （ q31;p13 ）：a case report and review of literatures

目的提高对慢性嗜酸细胞白血病（CEL）的认识水平。方法报告1例伴t（5；12）（q31；p13），FIP1样基因1（FIP1L1）血小板衍化生长因子（PDGFRα）（-）CEL的诊治过程。外周血及胸腔积液细胞的免疫表型采用流式细胞术（FCM）分析，染色体采用G显带分析，FIP1L1／PDGFRα融合基因表达采用RT-PCR技术检测，骨髓、肺及脾组织行常规病理学检查。结果1例16岁女性患者严重贫血、发热、脾大、血小板减少、嗜酸细胞显著增高，持续22个月。骨髓嗜酸细胞浸润伴纤维化改变；肺和脾组织均呈嗜酸细胞浸润，伴脾栓塞。克隆性染色体异常为t（5；12）（q31；p13），不表达FIP1L1／PDGFRα融合基因。外周血及胸腔积液细胞中除大量嗜酸细胞外，CD3^-、CD4^-、CD8^＋异常T淋巴细胞分别占淋巴细胞总数的5．43％和1．66％。患者对羟基脲、泼尼松、干扰素和甲磺酸伊马替尼（400mg／d共40d）治疗无效，小剂量阿糖胞苷、米托蒽醌、长春新碱、环磷酰胺、甲氨蝶呤、泼尼松等联合化疗仅有短期效果。患者最终死于心、肺、肝、肾多脏器功能衰竭。结论本例FIP1L1／PDGFRα（-）CEL符合WHO诊断标准，对多种药物及甲磺酸伊马替尼治疗无效，应在疾病早期尽早争取造血干细胞移植。CD3^-、CD4^-、CD8^＋克隆性T细胞异常与CEL发病的关系值得关注。

Objective To deepen the understanding of chronic eosinophilic leukemia （CEL） Methods The course of diagnosis and treatment in a case of FIP1L1/PDGFRα fusion gene negative CEL was reported. Flow cytometry was used to analyze the immunophenotype of the cells in peripheral blood and pleural fluid. Karyotype was analyzed with G-banding. The expression of FIP1L1/PDGFRα fusion gene was detected by RT-PCR technique. Routine pathological examination of the tissues from bone marrow, lung and spleen were performed. Result A sixteen-year-old girl had severe anemia, fever, splenomegaly, thrombocytopenia and dominant hypereosinophilia lasting for 22 months. Trephine biopsy showed a hypercellular marrow with eosinophilic proliferation and moderate reticular fibrosis. Eosinophilic infiltration was found in lung and spleen and embolism was also found in spleen. She had a clonal chromosomal abnormality t（5;12） （q31 ;p13 ） . The expression of FIP1L1/PDGFRα was negative. An abnormal clone of T cells expressing CD3^- ,CD4^- ,CD^8＋ was found in peripheral blood and pleural fluid, in which the clonal T cell accounted for 5.43% and 1.66% of the total lympbocytes respectively. The patient was refractory to treatment with hydroxyurea, prednisone and interferon alpha. She had poor response to a combination of therapy with low dose cytosine arabinoside, mitoxantrone, vincristine, cyclophosphamide, methotrexate and prednisone. She did not respond to imatinib and died of multiple organ failure. Conclusion The present case fulfilled the WHO diagnostic criteria of FIP1L1/PDGFRα（ - ） CEL which did not respond to routine treatment and imatinib. Allogenic stem cell transplantation should be considered as early as possible in this case. It is noteworthy that clonal CD3^-, CD4^-, CD^8＋ T-cell abnormality is related to the pathogenesis of CEL.