Hypereosinophilic Syndromes

Abstract

Knowledge of the cause(s) of the hypereosinophilic syndromes (HES) would greatly improve treatment options. Although it is unlikely that all patients with the HES will respond equally well to the same treatment, the use of currently available agents to lower the total eosinophil count to <10(9)/L can be lifesaving. Until recently, treatment of HES has been modelled after that of other haematological disorders by using combinations of various cytotoxic agents. This approach has led to the development of the current standard regimens of therapy. With improved understanding of the effects of corticosteroids and interferon-alpha (IFNalpha) on eosinophilopoiesis and on the actions of eosinophil-active cytokines, a new plateau has been reached where agents are targeted specifically to defeat uncontrolled eosinophilopoiesis. We now consider IFNalpha a first line agent for new HES patients as well as for controlling eosinophilia resistant to conventional therapy. IFNalpha as a single agent is effective for long term control of HES. Most patients respond to a dosage of 2 to 9 MU/day. Frequently, the dosage can be lowered after eosinophilia has been controlled. Sudden discontinuation of IFNalpha has resulted in recurrence of eosinophilia within weeks. If a suboptimal response occurs, prednisone or hydroxycarbamide (hydroxyurea) can be added. Resistance to IFNalpha may indicate development of a myeloproliferative or lymphoproliferative state or of eosinophilic leukaemia. As a new option for drug-resistant HES, allogeneic bone marrow transplantation should be considered. Although the number of patients is still small, within the past several years durable responses have been reported. Treatment of the cardiovascular sequelae of HES remains a therapeutic challenge. Improved cardiac surgery techniques have allowed many patients to benefit from ventricular decortication and valve replacement. It is important to combine control of eosinophilia with any operative intervention in HES because of the danger of recurrent disease if eosinophilia remains unchecked. Long term anticoagulation is probably indicated in patients with evident cardiac thrombus or peripheral vascular emboli; however, whether HES patients should routinely receive anticoagulants and whether continued anticoagulation should be given after eosinophilia has been controlled remain unanswered questions.