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.