Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome

Allergy. 2016 Jun;71(6):803-10. doi: 10.1111/all.12843. Epub 2016 Mar 2.


Background: 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).

Methods: 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 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.

Results: 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).

Conclusions: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.

Trial registration: NCT00044304 NCT00001406.

Keywords: PDGFRA-negative; eosinophilia; hypereosinophilic syndrome; imatinib; myeloid neoplasm.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Bone Marrow / pathology
  • Eosinophils
  • Female
  • Follow-Up Studies
  • Humans
  • Hypereosinophilic Syndrome / diagnosis*
  • Hypereosinophilic Syndrome / drug therapy*
  • Hypereosinophilic Syndrome / genetics
  • Imatinib Mesylate / therapeutic use*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Phenotype*
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Treatment Outcome
  • Young Adult
  • mRNA Cleavage and Polyadenylation Factors / genetics


  • Biomarkers
  • FIP1L1 protein, human
  • Protein Kinase Inhibitors
  • mRNA Cleavage and Polyadenylation Factors
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor alpha

Associated data