THE HYPEREOSINOPHILIC SYNDROMES AND MEPOLIZUMAB - OPEN LABEL

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。嗜酸性粒细胞增多综合征是一种罕见的疾病，与显著的血液嗜酸性粒细胞增多和组织损伤有关。存在不同的HES亚组，包括发作性血管性水肿和嗜酸性粒细胞增多综合征、NERDS综合征、伴有粘膜溃疡的HES患者和伴有T细胞克隆的患者。HES患者的一个主要区别是认识到一些患者对伊马替尼有反应。随后，又发现了另一个HES亚群，即血清类胰蛋白酶升高、骨髓中非典型梭形肥大细胞增加、预后不良和伊马替尼反应性的患者。 美泊利珠单抗是一种高亲和力的人源化单克隆抗IL-5，其消耗血液嗜酸性粒细胞并且显著地无副作用。对嗜酸性粒细胞增多综合征（HES）患者给予美泊利单抗使其受益，并可能减少了潜在的辅助性T细胞2优势。我们希望利用核心临床方案（MHE 100185）的开放标签扩展（MHE 100901）来了解mepolizumab对HES的影响。具体目标是确定美泊利单抗给药是否：1.对于因缺乏疗效而退出双盲mepolizumab方案的患者有效2。可以在间隔大于一个月3.通过长期给药（长达39个月）判断是安全的4。将揭示迄今尚未认识到的羟乙基淀粉异质性

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The hypereosinophilic syndrome is a rare disease associated with striking blood eosinophilia and tissue damage. Distinct HES subgroups exist including the episodic angioedema and eosinophilia syndrome, the NERDS syndrome, HES patients with mucosal ulcers and those with T cell clones. A major differentiation of HES patients resulted from recognition that some patients respond to imatinib. Subsequently, yet another HES subset was recognized namely patients with elevated serum tryptase, increased atypical spindle-shaped mast cells in the bone marrow, a poor prognosis and imatinib responsiveness . Mepolizumab is a high-affinity humanized monoclonal anti-IL-5 which depletes blood eosinophils and is remarkably free of side-effects. Mepolizumab administration to patients with the hypereosinophilic syndrome (HES) has benefited them and may have lessened the underlying T helper 2 predominance. We wish to take advantage of the open label extension (MHE 100901) of the core clinical protocol (MHE 100185) to understand the effects of mepolizumab on HES. Specific objectives are to determine whether mepolizumab administration: 1. Is effective for the treatment of patients who have withdrawn from the double-blind mepolizumab protocol because of lack of efficacy 2. Can be given at intervals greater than one month 3. Is safe as judged by administration over long periods of time (up to 39 months) 4. Will reveal HES heterogeneity not heretofore recognized