title: FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature.
abstract: We previously studied clinico-pathologic features of 89 consecutive adult patients with moderate-to-severe eosinophilia, and reported a FIP1L1-PDGFRA prevalence of 12%. In that series, all 11 FIP1L1-PDGFRA+ patients receiving imatinib achieved a complete response. We now extend our observations through a study of 741 unselected patients with eosinophilia for FIP1L1-PDGFRA, and present longer term follow up data for the imatinib-treated cohort. We also include data for three previously unreported FIP1L1-PDGFRA+ patients. Among the 741 requests, only 21 (3%) were found to carry the FIP1L1-PDGFRA mutation. While all 14 FIP1L1-PDGFRA+ patients receiving imatinib achieved a complete response, the 4 patients who attempted to discontinue imatinib all relapsed. We also find that it is possible to maintain patients in clinical remission with an empirically derived schedule of low-dose (50-100 mg), intermittent (once daily to once weekly) imatinib. Lastly, we present a comprehensive review of the literature pertaining to FIP1L1-PDGFRA in order to address several key aspects of this mutation from a clinical standpoint.
authors.affiliation: Divisions of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. pardanani.animesh@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.forename: R P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: C-Y
authors.initials: CY
authors.lastname: Li
authors.forename: M M
authors.initials: MM
authors.lastname: Patnaik
authors.forename: A P
authors.initials: AP
authors.lastname: Wolanskyj
authors.forename: M A
authors.initials: MA
authors.lastname: Elliott
authors.forename: J K
authors.initials: JK
authors.lastname: Camoriano
authors.forename: J H
authors.initials: JH
authors.lastname: Butterfield
authors.forename: G W
authors.initials: GW
authors.lastname: Dewald
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004802:Eosinophilia / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010879:Piperazines / Q000008:administration & dosage*; D015995:Prevalence; D011743:Pyrimidines / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
chemical_list: D001549:Benzamides; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha