title: Extended therapy with intravenous arginine butyrate in patients with beta-hemoglobinopathies.
abstract: BACKGROUND
  Enhanced production of fetal hemoglobin lessens the severity of beta-thalassemia and sickle cell disease. Intravenous infusion of arginine butyrate can increase the number of reticulocytes containing fetal hemoglobin in patients with these disorders, and it has induced a substantial increase in hemoglobin in one patient with thalassemia. We therefore tested the efficacy of this agent in patients with beta-hemoglobinopathies.
  
  
  METHODS
  We treated 10 patients with severe beta-thalassemia or sickle cell disease with arginine butyrate at an initial dose of 500 mg per kilogram of body weight per day (final dose, 2000 mg per kilogram per day), 6 days per week, for a mean (+/- SD) of 10 +/- 1.2 weeks (range, 9 to 13). A hematologic response was defined as an increase in the hemoglobin concentration of at least 2 g per deciliter in patients with thalassemia and as a twofold increase in the fetal hemoglobin concentration in patients with sickle cell disease.
  
  
  RESULTS
  Increase in gamma-globin messenger RNA and in reticulocytes containing fetal hemoglobin but not in hemoglobin were observed in the patients with thalassemia. A small, unsustained increase in fetal hemoglobin was observed in two patients with sickle cell disease. Drug toxicity was minimal at standard doses. One patient had a grand mal seizure after inadvertently receiving 2000 mg of arginine butyrate per kilogram over a period of six hours.
  
  
  CONCLUSIONS
  Ten weeks of intravenous arginine butyrate did not produce a hematologic response in 10 patients with either severe beta-thalassemia or sickle cell disease.
authors.affiliation: Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: G D
authors.initials: GD
authors.lastname: Sher
authors.forename: G D
authors.initials: GD
authors.lastname: Ginder
authors.forename: J
authors.initials: J
authors.lastname: Little
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: G J
authors.initials: GJ
authors.lastname: Dover
authors.forename: N F
authors.initials: NF
authors.lastname: Olivieri
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D001120:Arginine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002087:Butyrates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D002087:Butyrates; D006454:Hemoglobins; D001120:Arginine; C033018:arginine butyrate