THE HYPEREOSINOPHILIC SYNDROMES AND MEPOLIZUMAB

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 高嗜酸性粒细胞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亚型，包括发作性血管水肿和嗜酸性粒细胞增多综合征、NERDS综合征、HES黏膜溃疡患者和T细胞克隆患者。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亚型，即血清类胰蛋白酶升高、骨髓中非典型纺锤形肥大细胞增多、预后不良和对伊马替尼有反应的患者。 美波利单抗是一种高亲和力的人源化抗IL-5单抗，可去除血液中的嗜酸性粒细胞，且无明显副作用。甲波利单抗应用于高嗜酸性粒细胞综合征(HES)患者使他们受益，并可能减弱了潜在的T辅助2优势。我们希望利用核心临床方案(MHE 100901)的开放标签扩展(MHE 100185)来了解甲波利单抗对HES的影响。具体目标是确定甲波利单抗给药是否： 1.对因疗效不佳而退出双盲甲波利单抗方案的患者有效 2.可以间隔一个月以上给药 3.根据长时间(长达39个月)的管理判断是安全的 4.将揭示迄今未被认识到的HES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 Is effective for the treatment of patients who have withdrawn from the double-blind mepolizumab protocol because of lack of efficacy 2.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