Idiopathic Hypereosinophilic Syndrome (HES) with FIP1L1-PDGFRA Rearrangement Can Be Effectively Treated with Imatinib.

We studied 141 patients with HES, of which 55 primary HES (39%) defined as a peripheral blood eosinophilia greater than 1,500 cells/μL for longer than 6 months, absence of other apparent aetiologies for eosinophilia and symptoms of organ involvement. All patients were studied by molecular analysis for PDGFRB-TEL, FGFR1-BCR and BCR-ABL transcripts, frequently associated with HES/CMML/MDS syndrome: all these transcripts were absent in our series. We also sought for the recently reported involvement of PDGFRα, cryptically translocated with FIP1L1 in some HES pts responsive to Imatinib therapy: 13 pts (23%) were positive for the FIP1L1-PDGFRA rearrangement and all of them showed previously unreported, abnormal-sized fusion transcripts. Curiously, all FIP1L1-PDGFRA positive pts were male. We enrolled in a national clinical trial 31 (55%) primary HES pts, including all 13 (23%) FIP1L1-PDGFRA positive, with imatinib mesylate (100 to 400 mg/day). Median follow up of treatment was 4,5 moths (range 2–28). Rapid and complete haematological responses to imatinib therapy were recorded only in all FIP1L1-PDGFRA positive pts (100%) after one months of therapy and partial response in only one cases with HES without FIP1L1-PDGFRA fusion transcript. Complete molecular response without evidence of FIP1L1-PDGFRA transcript by qualitative RT-PCR was also recorded in all responding pts after median 2 months of therapy. We conclude that FIP1L1-PDGFRA rearrangement may be useful molecular marker of myeloproliferative HES, a predictor of imatinib-responsiveness and as a means to follow therapy in this subgroup of pts.