Hydroxyurea and sodium phenylbutyrate therapy in thalassemia intermedia

Hydroxyurea (HU) and sodium phenylbutyrate (SPB) have been shown to increas e fetal hemoglobin (Hb F) levels in patients with thalassemia intermedia. T he reported effects of these agents in increasing total Hb, however, have b een inconsistent and there have been no studies on the combination of these medications. We describe the clinical response, as determined by increases in total Hb and decreased transfusion needs, in five patients with thalass emia intermedia treated with HU alone or in combination with SPB, All of th e patients responded with increased levels of Hb F, but the responses in to tal Hb varied. Of the five patients, two had a marked response in total Hb in excess of 3 g/dl, two responded modestly with an increase in total Hb of 1-2 g/dl, and one did not respond. Prolonged responses were achieved with low doses of HU (3-10 mg/kg/day) and higher doses were associated with mild reversible hematologic or hepatic toxicity and no further increases in Hb. Sodium phenylbutyrate was added to treatment with HU in two patients, but failed to produce an increase in total Hb despite increasing Hb F levels. O f the four patients who responded to HU with an increase in total Hb, all r eported symptomatic improvement and three have not required further transfu sions, We conclude that low-dose HU therapy in patients with thalassemia in termedia may increase total Hb levels sufficiently to eliminate the need fo r transfusions. We, therefore, recommend a trial of HU for thalassemia inte rmedia patients in whom chronic transfusion therapy is being contemplated, (C) 1999 Wiley-Liss, Inc.