Hydroxyurea and sodium phenylbutyrate therapy in thalassemia intermedia

Abstract

Hydroxyurea (HU) and sodium phenylbutyrate (SPB) have been shown to increase fetal hemoglobin (Hb F) levels in patients with thalassemia intermedia. The reported effects of these agents in increasing total Hb, however, have been 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 thalassemia intermedia treated with HU alone or in combination with SPB. All of the patients responded with increased levels of Hb F, but the responses in total 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. Of the four patients who responded to HU with an increase in total Hb, all reported symptomatic improvement and three have not required further transfusions. We conclude that low-dose HU therapy in patients with thalassemia intermedia may increase total Hb levels sufficiently to eliminate the need for transfusions. We, therefore, recommend a trial of HU for thalassemia intermedia patients in whom chronic transfusion therapy is being contemplated.

Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia

“…After early case reports documented hematological improvements in b-thalassemia patients treated with hydroxyurea, 51,[58][59][60][61][62][63][64] several studies evaluated the efficacy and safety of the drug in this patient population (Table 1). 44,49,50, These primarily included small single-arm trials or retrospective cohort studies.…”

Hydroxyurea can eliminate transfusion requirements in children with severe β-thalassemia

“…1,2 A significant benefit could also be expected in patients with ␤-thalassemia, because the imbalance in globin chains could be ameliorated by the newly synthesized ␥-chains being able to neutralize the excess ␣-chains, which could partially correct ineffective erythropoiesis. Clinical and hematologic improvements have been reported in patients with thalassemia intermedia, [3][4][5][6][7][8] but responses in patients with thalassemia major are controversial. 5,9 We have followed 7 children with transfusiondependent ␤-thalassemia, 6 of them with severe transfusional complications, and have treated them with hydroxyurea in the hope that this drug could reduce transfusional needs.…”

Hydroxyurea in Thalassemia Major

“…Records of amount and frequency of blood transfusion were evaluated over one year of therapy and compared with control values using paired -T tests and correlation tests using SSPS version 15. P values of less than 0.05 were considered statistically significant.…”

“…However, higher doses were associated with mild reversible hematologic or hepatic toxicity and no further increase in hemoglobin. 15 We observed a significant decrease in blood transfusion requirement beginning in the first three to four months of HU therapy. Similar findings were reported by Bradi et al and Zamani F et al who evaluated the long-term efficacy and safety of hydroxyurea in major beta-thalassemic patients and observed substantial and persistent increase in total hemoglobin levels after first three and four months of hydroxyurea therapy respectively.…”