HYDROXYUREA THERAPY IN BETA-THALASSEMIA-INTERMEDIA - IMPROVEMENT IN HEMATOLOGICAL PARAMETERS DUE TO ENHANCED BETA-GLOBIN SYNTHESIS

The beta-thalassaemias represent a heterogenous group of diseases resu lting from decreased erythroid beta-globin mRNA expression and imbalan ced alpha/beta-globin chain synthesis which are manifest clinically by ineffective erythropoiesis and excessive haemolysis, Increasing level s of haemoglobin F (HbF) by pharmacological agents has been proposed t o ameliorate the severity of the disease by improving the balance in g lobin chain synthesis. Hydroxyurea (HU), as an effective agent with lo w toxicity for activating gamma-globin gene, has been shown to enhance HbF synthesis in experimental animals and in patients with sickle cel l anaemia. However, previous trials of HU in beta-thalassaemia patient s are ambiguous, with a small number having increased HbF synthesis. I n a recent study of Hll effects in Chinese beta-thalassaemia patients we unexpectedly found that two unrelated patients with beta-thalassaem ia intermedia demonstrated an improvement in the effectiveness of eryt hropoiesis reflected by an increase in haemoglobin concentration (from 4.1 to 6.3 g/dl, patient 1; from 6.5 to 9.7 g/dl, patient 2) and in r ed cell volume (from 68 to 104 fl, patient 1; from 68 to 85 fl, patien t 2) after a period of excess of 300 d of low-dosage HU treatment. The se effects, however, appear to be due to increased beta-globin biosynt hesis, because the percentage of HbF decreased in each patient as tota l Hb increased. This was reflected by changes in the alpha/beta ratio (from 0.301 to 0.581, patient 1; from 0.348 to 0.487, patient 2) with minimal changes in gamma-globin biosynthesis. We conclude that in addi tion to its known effects in stimulating gamma-globin production, hydr oxyurea may have a more general role in augmenting globin synthesis, i ncluding beta-globin in some thalassaemia intermedia patients who main tain the capacity to express normal beta-globin chains.