Myeloproliferative Hypereosinophilic Syndrome: Retrospective Analysis of Cytogenetic and Molecular Features
Monday, March 5, 2018
South Hall A2 (Convention Center)
Thanai Pongdee, MD FAAAAI, Irina Maric, Paneez Khoury, MD FAAAAI, Amy D. Klion, MD
RATIONALE: The myeloid subtype of hypereosinophilic syndrome (MHES) is associated with more aggressive disease, steroid unresponsiveness, and poor prognosis. Detection of the underlying molecular abnormality, such as FIP1L1-PDGFRA, is essential to determine an appropriate treatment approach.

METHODS: Forty-five subjects meeting clinical criteria for MHES were identified from a cohort of 485 subjects enrolled on a natural history study of eosinophilia from April 4, 1994 to June 21, 2017. All subjects were tested for FIP1L1-PDGFRA and BCR-ABL by reverse transcription nested PCR (RT-PCR), and 41/45 underwent bone marrow biopsy with cytogenetics and testing for D816V KIT. Results of prior bone marrow examinations and genetic mutation testing were extracted from outside records.

RESULTS: Prior evaluation for mutations associated with MHES was highly variable and included testing for abnormalities in PDGFRA, JAK2, PDGFRB, and FGFR1 in 53%, 31%, 29% and 20% of subjects, respectively. Among those tested, 38% were positive for FIP1L1-PDGFRA and 21% for JAK2 mutations. Translocations involving PDGFRB or FGFR1 were identified in one subject each. Of significance, 5 subjects (33%) who had tested negative for FIP1L1-PDGFRA by fluorescence in situ hybridization (FISH) were later found to be FIP1L1-PDGFRA-positive by RT-PCR. These initial false negative results led to delays in initiating imatinib, the treatment of choice for this subtype of MHES.

CONCLUSIONS: With the increasing availability of targeted therapies, systematic evaluation for genetic mutations is essential in evaluating patients with MHES. If FISH testing for FIP1L1-PDGFRA is negative and no other etiology is found, RT-PCR and/or empiric imatinib should be considered.