Imatinib has limited therapeutic activity for hypereosinophilic syndrome patients with unknown or negative PDGFRalpha mutation status.

Hypereosinophilic syndrome (HES) is characterized by sustained non-clonal blood and tissue eosinophilia, leading to end-organ damage. With a molecular/cytogenetic clonality marker, the disease is classified as chronic eosinophilic leukemia (CEL). Efficacy of imatinib mesylate is well established in CEL with FIP1L1-platelet-derived growth factor-alpha (PDGFRalpha) rearrangement. We treated with imatinib 18 HES patients (11 PDGFRalpha-negative and 7 PDGFRalpha-status unknown). One patient with unknown PDGFRalpha status achieved complete hematologic response, and two (one PDGFRalpha negative and one status unknown) achieved partial hematologic response. Our results confirm low response rate to imatinib in HES patients with unknown or negative PDGFRalpha status, and underscore the need for new therapeutic options for this disorder.