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

The butyrate derivative isobutyramide (IBT) increases fetal hemoglobin (HbF ) in patients with P-hemoglobinopathies, but little is known about its usef ulness for prolonged therapeutic use. We treated 8 patients with transfusio n-dependent P-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 mai ntained between 85 g/L (range 82-87 g/L) (pretransfusion) and 115 g/L (rang e 110-119 g/L) (post-transfusion) (median, interquartile range), correspond ing 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 pati ent, resulting in a decrease of daily iron load from 455 <mu>g/kg per day ( range 451-459 mug/kg per day) before therapy to 211 mug/kg per day (range 2 03-286 mug/kg per day) during the 12-month treatment period. Prolongation o f transfusion intervals achieved by IBT was less consistent in another pati ent, whose parenteral iron load nevertheless decreased from 683 mug/kg per day (range 618-748 mug/kg per day) to 542 mug/kg per day (340-596 mug/kg pe r day). In the other 6 patients, no prolongation of transfusion intervals w as achieved. Response to treatment was associated with high pretreatment Hb F (> 4.5%), high parental HbF, and increased erythropoietin levels (> 150 I U/L). We conclude that IBT prolongs transfusion intervals and reduces paren teral iron burden in some patients with transfusion-dependent beta -thalass emia, (C) 2000 by The American Society of Hematology.