Elimination of transfusions through induction of fetal hemoglobin synthesis in Cooley's anemia

Pharmacological stimulation of fetal hemoglobin production is of considerable interest as an alternative approach to therapy for Cooley's anemia. While intravenous compounds have been effective in inducing short-term increases in fetal hemoglobin in a few patients, long-term elimination of transfusion requirement has not been reported. In patients with Cooley's anemia, treatment with oral sodium phenylbutyrate alone, sodium phenylbytyrate combined with hydroxyurea, and hydroxyurea alone, has augmented fetal hemoglobin production and increased total hemoglobin concentration as much as 5 g/dl over baseline eliminating transfusion requirement in two patients. Parallel declines in circulating nucleated red cell count, and concentrations of serum transform receptor and erythropoietin, are consistent with more effective erythropoiesis. Over extended periods of treatment, no induction of other fetal proteins and no adverse effects were observed. Particular disease mutations and other genetic factors may be of prime importance in determining the response to agents that induce production of fetal hemoglobin.