Extended Therapy with Intravenous Arginine Butyrate in Patients with (beta)-Hemoglobinopathies

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

From the Hospital for Sick Children and the University of Toronto, Toronto (G.D.S., N.F.O.); the University of Minnesota School of Medicine, Minneapolis (G.D.G., J.L., S.Y.); and Johns Hopkins University School of Medicine, Baltimore (G.J.D.). Address reprint requests to Dr. Olivieri at the Haemoglobinopathy Program, Hospital for Sick Children, Rm. 6324, 555 University Ave., Toronto, ON M5G 1X8, Canada.
Supported in part by the Connaught Transformative Research Grant Program, University of Toronto; the Medical Research Council of Canada; the Ontario Heart and Stroke Foundation; the Cooley's Anemia Foundation; and the National Institutes of Health (DK 29902). Dr. Olivieri is a Career Scientist of the Ontario Ministry of Health.

New England Journal of Medicine 332(24):p 1606-1610, June 15, 1995.

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 fetal hemoglobin in patients with sickle cell disease.

Results

There were increases in (gamma)-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 (beta)-thalassemia or sickle cell disease. (N Engl J Med 1995;332:1606-10.)