Effect of Hydroxyurea on the Level of Ineffective Erythropoiesis, Transfusion Requirement, and Fetal Hemoglobin Synthesis in Patients With Beta-Thalassemia-Intermedia

Individuals with homozygous beta thalassemia are either severely anemic or dependent on blood transfusion to sustain life. Deficient synthesis of the beta chain leads to imbalanced chain synthesis with an excess of alpha globin. This alpha globin precipitates, causing ineffective erythropoiesis and shortened red cell survival. Hydroxyurea is a cell-cycle specific agent that blocks DNA synthesis by inhibiting ribonuclease reductase, the enzyme that converts ribonucleotides to deoxyribonucleotides. Administration of hydroxyurea to primates and more than 300 patients with sickle cell anemia has been frequently, but not invariably associated with a substantial increase in synthesis of gamma globin. In patients with homozygous beta-thalassemia, enhanced gamma globin synthesis could partially compensate for the deficient synthesis of beta globin rendering chain synthesis more balanced and reducing the relative excess of alpha chains. The purpose of this protocol is to test the hypothesis that chronic daily low dose administration of hydroxyurea will enhance gamma globin synthesis, increase red cell production and partially or substantially correct the anemia in patients with homozygous beta-thalassemia. The effect of treatment will be monitored by serial determination of the hemoglobin and hematocrit. The relationship between response to therapy and the specific beta-globin mutation(s) will also be analyzed. This study will therefore examine a cohort of patients not previously treated with hydroxyurea.