Response to hydroxyurea treatment in Iranian transfusion-dependent beta-thalassemia patients

Abstract

BACKGROUND AND OBJECTIVES: Hydroxyurea (HU) is known to increase gamma-globin chain expression in postnatal life. The efficacy of HU treatment in thalassemia patients is still unclear. The aim of this study was to monitor treatment of a large cohort of patients with beta-thalassemia major in order to establish the response to HU and the associated elements. DESIGN AND METHODS: HU therapy was started in 133 patients diagnosed with transfusion-dependent beta-thalassemia in 1999. The molecular background of the disease, the polymorphisms of the promoter region of the genes, the haplotype of the beta-globin gene cluster, the alpha-gene deletions and the HS2 polymorphism at the locus control region (LCR) of the beta-globin gene cluster were studied. RESULTS: We were able to classify three categories of response: a good response (61%) in patients who shifted from monthly blood transfusion dependency to a stable transfusion-free condition at an average Hb level of more than 10 gm/dL; a moderate response (23%) in patients who remained transfusion dependent but at longer intervals (6 months or more), and non response in patients who, after one year of treatment, remained at the same level of transfusion dependency. The correlations with the molecular defects were found to be secondary to the presence of the (C-->T) at -158 of the Ggamma gene (XmnI polymorphism). The T allele, in linkage to the haplotype I (+----) and to the internal beta-globin gene framework 2, was the most significant modulating factor involved. INTERPRETATION AND CONCLUSIONS: The good response to HU treatment that a significant number of southwest Iranian patients with beta-thalassemia patients had seems to correlate with particular haplotypes. This indicates that HU treatment is a sensible option for transfusion-dependent beta-thalassemia patients with a favorable molecular background.