European Multicenter Experience on Idiopathic Hypereosinophilic Syndrome (HES) with FIP1L1-PDGFRA Rearrangement treated with Imatinib.

Idiopathic hypereosinophilic syndrome (HES) is an infrequent hematological disorder characterized by persistent eosinophilia with organ involvement, often presenting to other medical specialists. We studied 89 primary HES 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 negative by molecular analysis for TEL-PDGFRB, and/or BCR-ABL transcripts, frequently associated with HES/CMML/MDS syndromes. We also sought for the recently reported involvement of PDGFRalpha, cryptically fused with FIP1L1 in some HES patients responsive to Imatinib therapy: 34 patients were positive for the FIP1L1-PDGFRA rearrangement and all of them showed previously unreported, abnormal-sized fusion transcripts. A specific RT-PCR assay has been set up for this analysis and a quantitative Q-RT-PCR Taqman assay is in development. Of note, all FIP1L1-PDGFRA positive patients were male. 56 out of 89 (62%) primary HES patients, including 31/34 FIP1L1-PDGFRA positive, were sensitive to imatinib mesylate (100 to 400 mg/daily). Median follow up of treatment was 10 months (range 2–28). Rapid and complete haematological responses (CHR) to imatinib therapy were recorded in all FIP1L1-PDGFRA positive patients (91%) after one month of therapy and partial response in nine cases with HES but without FIP1L1-PDGFRA fusion transcript. Complete molecular response without evidence of FIP1L1-PDGFRA transcript by qualitative RT-PCR was also recorded in the majority of responding patients after median 2 months of therapy, however in few cases the complete molecular response could be recognised only after more than 18 months of imatinib therapy. We conclude that FIP1L1-PDGFRA rearrangement is a useful molecular marker of myeloproliferative HES, a predictor of imatinib-responsiveness and as a means to follow therapy in this subgroup of patients.