title: Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome.
abstract: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES).
  
  
  
  Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 × 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study.
  
  
  
  Overall, imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36).
  
  
  
  Clinical features of MHES predict imatinib response in PDGFRA-negative HES.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Khoury
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.|Department of Hematology, Tallaght Hospital, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Desmond
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pabon
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Holland-Thomas
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Ware
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Arthur
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kurlander
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Fay
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: I
authors.initials: I
authors.lastname: Maric
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Klion
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D004804:Eosinophils; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
chemical_list: D015415:Biomarkers; C479818:FIP1L1 protein, human; D047428:Protein Kinase Inhibitors; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: PDGFRA-negative; eosinophilia; hypereosinophilic syndrome; imatinib; myeloid neoplasm