Hydroxyurea therapy in β-thalassaemia intermedia: improvement in haematological parameters due to enhanced β-globin synthesis

Summary. The β-thalassaemias represent a heterogenous group of diseases resulting from decreased erythroid β-globin mRNA expression and imbalanced a/β-globin chain synthesis which are manifest clinically by ineffective erythropoiesis and excessive haemolysis. Increasing levels of haemoglobin F (HbF) by pharmacological agents has been proposed to ameliorate the severity of the disease by improving the balance in globin chain synthesis. Hydroxyurea (HU), as an effective agent with low toxicity for activating 7-globin gene, has been shown to enhance HbF synthesis in experimental animals and in patients with sickle cell anaemia. However, previous trials of HU in β-thalassaemia patients are ambiguous, with a small number having increased HbF synthesis. In a recent study of HU effects in Chinese j3 -thalassaemia patients we unexpectedly found that two unrelated patients with β-thalassaemia intermedia demonstrated an improvement in the effectiveness of erythropoiesis reflected by an increase in haemoglobin concentration (from 4-1 to 6-3 g/dl, patient 1; from 6-5 to 97 g/dl, patient 2) and in red cell volume (from 68 to 104 fl, patient 1; from 68 to 85 fl, patient 2) after a period of excess of 300 d of low-dosage HU treatment. These effects, however, appear to be due to increased,3-globin biosynthesis, because the percentage of HbF decreased in each patient as total Hb increased. This was reflected by changes in the β/a ratio (from 0'301 to 0-581, patient 1; from 0'348 to 0-487, patient 2) with minimal changes in 7-globin biosynthesis. We conclude that in addition to its known effects in stimulating 7-globin production, hydroxyurea may have a more general role in augmenting globin synthesis, including β-globin in some thalassaemia intermedia patients who maintain the capacity to express normal β-globin chains.