THE HYPEREOSINOPHILIC SYNDROMES AND MEPOLIZUMAB

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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 Is effective for the treatment of patients who have withdrawn from the double-blind mepolizumab protocol because of lack of efficacy 2.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