Oral isobutyramide reduces transfusion requirements in some patients with homozygous beta-thalassemia.

The butyrate derivative isobutyramide (IBT) increases fetal hemoglobin (HbF) in patients with beta-hemoglobinopathies, but little is known about its usefulness for prolonged therapeutic use. We treated 8 patients with transfusion-dependent beta-thalassemia with 350 mg/kg of body weight per day of oral IBT for 126 to 384 days. During the trial period, the hemoglobin level was maintained between 85 g/L (range 82-87 g/L) (pretransfusion) and 115 g/L (range 110-119 g/L) (post-transfusion) (median, interquartile range), corresponding to 4-week transfusion intervals in all patients during the pretreatment phase. Adverse effects (bitter taste, epigastric discomfort) did not cause discontinuation of IBT. HbF increased in all patients from 3.1% (range 1.9%-4.8%) to 6.0% (range 3.3%-8.7) (P =.0017), while free Hb dropped from 0.48 g/L (range 0.39-0.81 g/L) to 0.19 g/L (range 0.16-0.24 g/L) (P <.0001). Transfusion intervals were consistently extended to 8 or 9 weeks in 1 patient, resulting in a decrease of daily iron load from 455 microgram/kg per day (range 451-459 microgram/kg per day) before therapy to 211 microgram/kg per day (range 203-286 microgram/kg per day) during the 12-month treatment period. Prolongation of transfusion intervals achieved by IBT was less consistent in another patient, whose parenteral iron load nevertheless decreased from 683 microgram/kg per day (range 618-748 microgram/kg per day) to 542 microgram/kg per day (340-596 microgram/kg per day). In the other 6 patients, no prolongation of transfusion intervals was achieved. Response to treatment was associated with high pretreatment HbF (> 4.5%), high parental HbF, and increased erythropoietin levels (> 150 IU/L). We conclude that IBT prolongs transfusion intervals and reduces parenteral iron burden in some patients with transfusion-dependent beta-thalassemia.