Steroid Treatment for Hypereosinophilic Syndrome

This study aims to develop a model to determine whether a single, oral, weight-based dose of glucocorticoid (GC) can predict clinical and biologic response to GC s over the long term in subjects with hypereosinophilic syndrome (HES). Subjects with FIP1L1/PDGFRalpha-negative HES, who are symptomatic with eosinophil count >1500/microL and receiving less than or equal to10 mg prednisone daily, will be enrolled. A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) will be administered. Eosinophil count and various laboratory parameters will be assessed at 2 hours, 4 hours and 24 hours following prednisone administration (investigators will be blinded to the results of the eosinophil counts). The subjects will then begin GC therapy at 30 mg prednisone daily followed by a standardized taper. The lowest dose of GC at which symptoms and eosinophilia are controlled will be compared to the change in eosinophil count at 2, 4 and 24 hours post-challenge. Mechanisms and in vitro correlates of GC resistance will also be explored.

• SUBJECT INCLUSION CRITERIA:

Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all of the following criteria apply:

• Subjects must be 7 years of age or older to enroll
• Subject meets diagnostic criteria for HES (AEC >1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia)
• AEC greater than 1500 microL obtained within 14 days prior to enrollment
• Willingness to perform the timed steroid challenge
• Appropriate candidate for GC treatment after challenge
• Willingness to have samples stored for future research

SUBJECT EXCLUSION CRITERIA:

A subject will not be eligible to participate in the study if any of the following apply:

• Receiving >10 mg prednisone or equivalent at the time of enrollment.
• Receiving less than or equal to 10 mg of prednisone or equivalent but have not been on a fixed dose for at least 3 weeks (subjects on a current corticosteroid taper will be excluded).
• AEC less than or equal to 1500/microl on the day of the steroid challenge
• Use of immunomodulatory medications, (other than less than or equal to 10 mg/day prednisone) including but not limited to biologics, within the past 6 months.
• Pregnant at the time of screening.
• Have a known mutation in the FIP1L1-PDGFR gene.
• Any condition that, in the opinion of the investigator, places the subject at undue risk by participating in the protocol.
• Weight less than 48 kg (106 lbs) in subjects less than 18 years of age.