Response to hydroxyurea therapy in β-thalassemia

Although a relatively small number of previous studies suggest a modest response to hydroxyurea (HU) therapy in β-thalassemia, more recent investigations have revealed that some transfusion-dependent patients can become transfusion-independent following HU therapy. Patients with Gγ XmnI polymorphism, several β-globin mutations, and α-thalassemia deletions were inconsistently reported to have significant responses to HU therapy. To better predict who may respond, we retrospectively evaluated the clinical response and the molecular background of 18 β-thalassemia patients treated with HU for a mean of 46 months. The majority of transfusion-dependent patients responded to HU therapy with 9 out of 11 (82%) becoming transfusion-independent. Five thalassemia intermedia (TI) patients receiving occasional blood transfusion did not require any additional transfusions following therapy and two TI patients who had never received transfusions had a 2 g/dl increase in their hemoglobin level. The majority of β-thalassemia major patients who became transfusion-independent (7/9) were either homozygous (5) or heterozygous (2) for the XmnI polymorphism. No correlation was identified between response to therapy and the presence of specific β-thalassemia mutations or α-globin deletions. We conclude that further analysis of the degree of response of transfusion-dependent β-thalassemia patients to HU therapy, as well as, the impact of their genetic background on this response is required to identify patients likely to have significant response.