Extended therapy with intravenous arginine butyrate in patients with β-hemoglobinopathies

Graham D. Sher, Gordon D. Ginder, Jane Little, Suya Yang, George J Dover, Nancy F. Olivieri

Research output: Contribution to journalArticle

Abstract

Background. Enhanced production of fetal hemoglobin lessens the severity of β-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 β-hemoglobinopathies. Methods. We treated 10 patients with severe β-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 fetal hemoglobin in patients with sickle cell disease. Results. There were increases in γ-globin messenger RNA and in reticulocytes containing fetal hemoglobin, but no increases in hemoglobin, 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 β-thalassemia or sickle cell disease.

Original languageEnglish (US)
Pages (from-to)1606-1610
Number of pages5
JournalNew England Journal of Medicine
Volume332
Issue number24
StatePublished - May 15 1995

Fingerprint

Hemoglobinopathies
Thalassemia
Fetal Hemoglobin
Sickle Cell Anemia
Hemoglobins
Therapeutics
Reticulocyte Count
arginine butyrate
Globins
Reticulocytes
Proxy
Drug-Related Side Effects and Adverse Reactions
Intravenous Infusions
Seizures
Body Weight
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sher, G. D., Ginder, G. D., Little, J., Yang, S., Dover, G. J., & Olivieri, N. F. (1995). Extended therapy with intravenous arginine butyrate in patients with β-hemoglobinopathies. New England Journal of Medicine, 332(24), 1606-1610.

Extended therapy with intravenous arginine butyrate in patients with β-hemoglobinopathies. / Sher, Graham D.; Ginder, Gordon D.; Little, Jane; Yang, Suya; Dover, George J; Olivieri, Nancy F.

In: New England Journal of Medicine, Vol. 332, No. 24, 15.05.1995, p. 1606-1610.

Research output: Contribution to journalArticle

Sher, GD, Ginder, GD, Little, J, Yang, S, Dover, GJ & Olivieri, NF 1995, 'Extended therapy with intravenous arginine butyrate in patients with β-hemoglobinopathies', New England Journal of Medicine, vol. 332, no. 24, pp. 1606-1610.
Sher, Graham D. ; Ginder, Gordon D. ; Little, Jane ; Yang, Suya ; Dover, George J ; Olivieri, Nancy F. / Extended therapy with intravenous arginine butyrate in patients with β-hemoglobinopathies. In: New England Journal of Medicine. 1995 ; Vol. 332, No. 24. pp. 1606-1610.
@article{415007e8bf2b4dc2b2db381ca8783f6d,
title = "Extended therapy with intravenous arginine butyrate in patients with β-hemoglobinopathies",
abstract = "Background. Enhanced production of fetal hemoglobin lessens the severity of β-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 β-hemoglobinopathies. Methods. We treated 10 patients with severe β-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 fetal hemoglobin in patients with sickle cell disease. Results. There were increases in γ-globin messenger RNA and in reticulocytes containing fetal hemoglobin, but no increases in hemoglobin, 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 β-thalassemia or sickle cell disease.",
author = "Sher, {Graham D.} and Ginder, {Gordon D.} and Jane Little and Suya Yang and Dover, {George J} and Olivieri, {Nancy F.}",
year = "1995",
month = "5",
day = "15",
language = "English (US)",
volume = "332",
pages = "1606--1610",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "24",

}

TY - JOUR

T1 - Extended therapy with intravenous arginine butyrate in patients with β-hemoglobinopathies

AU - Sher, Graham D.

AU - Ginder, Gordon D.

AU - Little, Jane

AU - Yang, Suya

AU - Dover, George J

AU - Olivieri, Nancy F.

PY - 1995/5/15

Y1 - 1995/5/15

N2 - Background. Enhanced production of fetal hemoglobin lessens the severity of β-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 β-hemoglobinopathies. Methods. We treated 10 patients with severe β-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 fetal hemoglobin in patients with sickle cell disease. Results. There were increases in γ-globin messenger RNA and in reticulocytes containing fetal hemoglobin, but no increases in hemoglobin, 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 β-thalassemia or sickle cell disease.

AB - Background. Enhanced production of fetal hemoglobin lessens the severity of β-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 β-hemoglobinopathies. Methods. We treated 10 patients with severe β-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 fetal hemoglobin in patients with sickle cell disease. Results. There were increases in γ-globin messenger RNA and in reticulocytes containing fetal hemoglobin, but no increases in hemoglobin, 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 β-thalassemia or sickle cell disease.

UR - http://www.scopus.com/inward/record.url?scp=0029032965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029032965&partnerID=8YFLogxK

M3 - Article

VL - 332

SP - 1606

EP - 1610

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 24

ER -