title: Oral isobutyramide reduces transfusion requirements in some patients with homozygous beta-thalassemia.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology/Hematology, Charité, Humboldt University, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Reich
authors.forename: C
authors.initials: C
authors.lastname: Bührer
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: D
authors.initials: D
authors.lastname: Ohlendorf
authors.forename: M
authors.initials: M
authors.lastname: Mesche
authors.forename: P
authors.initials: P
authors.lastname: Sinha
authors.forename: A
authors.initials: A
authors.lastname: Kage
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: B
authors.initials: B
authors.lastname: Vetter
authors.forename: A E
authors.initials: AE
authors.lastname: Kulozik
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001769:Blood / Q000187:drug effects; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D004909:Erythrocyte Indices / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005319:Fetal Hemoglobin / Q000187:drug effects / Q000378:metabolism; D005838:Genotype; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D010349:Patient Compliance; D013997:Time Factors; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D006454:Hemoglobins; D004921:Erythropoietin; C030197:isobutyramide; D005319:Fetal Hemoglobin; D007501:Iron