The efficacy of imatinib mesylate in patients with FIP1L1-PDGFR{alpha}-positive hypereosinophilic syndrome. Results of a multicenter prospective study

From Department of Hematology-Oncology "L. and A. Seràgnoli", University of Bologna, and S.Orsola-Malpighi University Hospital, Bologna (MB, MR, EO, NT, AdV, II, SP, SS, GR, GM); Department of Clinical and Biological Sciences, University of Turin at Orbassano, and S.Luigi Gonzaga Hospital, Orbassano (DC,FM, EG, EG, GS); Division of Hematology, IRCCS S. Matteo, Pavia (SM); Division of Hematology, Udine University and General Hospital, Udine (MT); Division of Hematology, University Tor Vergata, Rome (FB); CEINGE Advanced Biotechnologies and Department of Biochemistry and Medical Biotechnology, University Federico II, Naples (CA, FP) Correspondence: Michele Baccarani, Department of Hematology-Oncology "L. and A. Seràgnoli", S.Orsola-Malpighi University Hospital, Via Massarenti, 9 40138 Bologna, Italy. E-mail: michele.baccarani{at}unibo.it Background and Objectives: The hypereosinophilic syndrome (HES) may be associated with the fusion of the platelet derived growth factor receptor ( PDGFR ) gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated PDGFR tyrosine kinase. These cases with FIP1L1-PDGFR rearrangement have been reported to be very sensitive to the tyrosine kinase inhibitor imatinib mesylate. Design and Methods: A prospective multicenter study of idiopathic or primary HES was established in 2001 (Study Protocol Registration no. NCT 0027 6929). One hundred and ninety-six patients were screened, of whom 72 where identified as having idiopathic or primary HES and 63 were treated with imatinib 100 to 400 mg daily. Results: Twenty-seven male patients carried the FIP1L1-PDGFR rearrangement. All 27 achieved a complete hematologic remission (CHR) and became negative for the fusion transcripts according to reverse transcriptase polymerase chain reaction (RT-PCR) analysis. With a median follow-up of 25 months (15–60 months) all 27 patients remain in CHR and RT-PCR negative, and continue treatment at a dose of 100 to 400 mg daily. In three patients imatinib treatment was discontinued for few months, the fusion transcript became rapidly detectable, and then again undetectable upon treatment reassumption. Thirty-six patients did not carry the rearrangement; of these, five (14%) achieved a CHR, which was lost in all cases after 1 to 15 months. Interpretation and Conclusions: All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFR rearrangement. For all patients with this rearrangement, chronic