Management of Hypereosinophilic Syndrome

Abstract

Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by unexplained persistent primary eosinophilia causing end-organ damage. We conducted a prospective cohort study of patients fulfilling the diagnostic criteria for HES. Of 20 patients considered eligible for the study, 2 were found to have clonal myeloid disorders, limiting the diagnosis of "true" HES to 18 patients. No patient carried the FIP1L1-PDGFRA fusion gene or other imatinib-responsive translocations. A clonal interleukin-5-producing T-cell population was not detected in any patient. Common manifestations at presentation were pulmonary, cutaneous, and neurologic involvement; serositis; and gastrointestinal involvement. Only 3 patients developed cardiac involvement. Fifteen of the HES patients were administered first-line combined treatment with steroids and hydroxyurea. Nine patients achieved complete response, while 6 attained only partial response. Imatinib was administered to 3HES patients who had been pretreated with steroids, resulting in complete hematologic and clinical response in 2 patients and no response at all in 1. Further treatment of the latter patient with steroids and hydroxyurea also proved ineffective. We conclude that the therapeutic approach should be individualized according to molecular findings. We consider the coadministration of corticosteroids and hydroxyurea to be an effective combination for the treatment of FIP1L1-PDGFRA-negative HES. Abbreviations: ABL = Abelson murine leukemia viral oncogene homolog, ANCA = anti-neutrophil cytoplasmic antibodies, ARMS = amplification refractory mutation system, CML = chronic myeloid leukemia, CT = computerized tomography, ELISA = enzyme-linked immunosorbent assay, HES = hypereosinophilic syndrome, IL-5 = interleukin-5, MPD = myeloproliferative disorder, PCR = polymerase chain reaction, PDGFRA = platelet-derived growth factor alpha, RT-PCR = reverse transcription-PCR, SM = systemic mastocytosis, TCR = T-cell receptor, WBC = white blood cells.