Pharmacological induction of foetal haemoglobin synthesis in sickle-cell disease.

Abstract In the present review the role and regulation of foetal haemoglobin (HbF) in sickle-cell disease as well as the clinical results of therapy aimed at augmenting HbF synthesis are briefly discussed. Enhanced levels of HbF have an inhibitory effect on sickling and ameliorate the clinical course of sickle-cell disease. This knowledge has incited a search for pharmacological agents capable of stimulating HbF production. Cytostatic drugs, in particular hydroxyurea, but also other agents such as erythropoietin, butyrate and its analogues have been shown to induce HbF production. The mechanisms of action and the clinical effects of these agents are summarized. Only hydroxyurea has shown significant clinical effects in terms of reduction of pain-crises, chest syndrome and transfusions in sickle-cell patients. However, not all patients experience clinical amelioration and it appears difficult to predict which patient will gain from hydroxyurea therapy. Further studies need to expand the clinical experience with hydroxyurea, other HbF-inducing agents and combinations of these drugs. Moreover, they will hopefully provide criteria to enable appropriate selection of those patients with sickle-cell anaemia who will benefit clinically from HbF stimulation, also taking into account the risks and costs of long-term pharmacological therapy.