Fetal haemoglobin augmentation in E/beta(0) thalassaemia: clinical and haematological outcome

Abstract

Patients with E/beta(0) thalassaemia, the most common haemoglobinopathy in many Asian countries, might benefit from drugs that increase fetal and total haemoglobin and thereby decrease the need for transfusions. The long-term clinical efficacy and safety of such therapy is unknown, limiting its use in countries where resources for safe and regular transfusion are scarce. In this study, 45 patients were treated with hydroxyurea (18-20 mg/kg) for 24+/-9 months, hydroxyurea with sodium phenyl butyrate (n=8) and hydroxyurea with erythropoietin (n=9), each for approximately 6 months, and followed for 3 years from study exit. Hydroxyurea had minimal toxicity, resulted in a mean 1.3 g/dl steady-state increase in haemoglobin in 40% of patients, and a milder response (<OR=1 g/dl) in the others. Baseline haemoglobin F was significantly associated with an increase in haemoglobin (P<0.001). Combined treatment with erythropoietin benefited selected patients, but the addition of sodium phenyl butyrate had no effect. Of the 27/45 patients who discontinued regular transfusions before the study, 13 remained transfusion independent during long-term follow-up, 6/13 continued hydroxyurea. Hydroxyurea moderately increased steady-state haemoglobin in a sub-group of E/beta(0) thalassaemia patients and can be considered for patients with intermediate severity disease, thus delaying or avoiding the need for life-long transfusions. Continuous monitoring of toxicity and growth is required.