Chrobák L, Voglová J
Oddelení klinické hematologie II. interní kliniky Lékaeské fakulty UK a FN, Hradec Králové.
Vnitr Lek. 2005 Dec;51(12):1385-93.
Idiopathic hypereosinophilic syndrome is a heterogenous group of hematological disorders characterized by eosinophilia (> 1.5 x 10(9)/l) persistent for more than 6 months, exclusion of reactive eosinophilia from other causes, such as parasitic infections or allergy, and evidence of end-organ damage. According to World Health Organization the exclusion includes all neoplastic disorders in which eosinophils are part of the neoplastic clone. Excluded should be also T cell population with aberant phenotype and abnormal cytokine production, recently considert also as "lymphocytic" variants of the HES [42]. HES has to be reclassified as chronic eosinophilic leukemia (CEL) when there is evidence for clonality based on the presence of chromosomal abnormalities or inactivation of X-chromosome in female patients. The successful empiric treatment of patients with tyrosine kinase inhibitor imatinib (Glivec) suggested the presence of an imatinib-sensitive tyrosine kinase inhibitor. The identification of a specific intersticial chromosome deletion del(4)(q12;q12) creating the FIP1L1-PDGFRA fusion gene confirmed this hypothesis. Patients carrying this gene should be reclassified as CEL and detection of this gene is a positive predictor for response to imatinib therapy. Effective doses of imatinib are 100 mg/day. The side effects are minimal. The only exception is an acute left ventricular dysfunction which has been reported in three patients within the first week of treatment with imatinib. Imatinib has been successfully used also in some patients with the constitutively activated thyrosine kinase ETV6-PDGFRbeta [1] and in systemic mast cell disease associated with eosinophilia. Other therapeutical options for HES/CEL have been mentioned. The resistence to imatinib and the possibilities how to overcome it are discussed.
特发性嗜酸性粒细胞增多综合征是一组异质性血液系统疾病，其特征为嗜酸性粒细胞增多（>1.5×10⁹/L）持续超过6个月，排除其他原因引起的反应性嗜酸性粒细胞增多，如寄生虫感染或过敏，并有终末器官损害的证据。根据世界卫生组织的标准，排除范围包括所有嗜酸性粒细胞是肿瘤克隆一部分的肿瘤性疾病。具有异常表型和细胞因子产生异常的T细胞群体也应排除，最近也被视为HES的“淋巴细胞性”变异型[42]。当基于染色体异常的存在或女性患者X染色体失活有克隆性证据时，HES必须重新分类为慢性嗜酸性粒细胞白血病（CEL）。酪氨酸激酶抑制剂伊马替尼（格列卫）对患者的成功经验性治疗提示存在对伊马替尼敏感的酪氨酸激酶。特定的间质染色体缺失del(4)(q12;q12)产生FIP1L1-PDGFRA融合基因的鉴定证实了这一假设。携带该基因的患者应重新分类为CEL，该基因的检测是对伊马替尼治疗反应的阳性预测指标。伊马替尼的有效剂量为100mg/天。副作用极小。唯一的例外是在伊马替尼治疗的第一周内有3例患者报告出现急性左心室功能障碍。伊马替尼也已成功用于一些具有组成性激活的酪氨酸激酶ETV6-PDGFRβ的患者[1]以及与嗜酸性粒细胞增多相关的系统性肥大细胞病。还提到了HES/CEL的其他治疗选择。讨论了对伊马替尼的耐药性以及克服它的可能性。
