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Induction of fetal hemoglobin production in subjects with sickle cell
anemia by oral sodium phenylbutyrate
GJ Dover, S Brusilow and S Charache
Department of Pediatrics, Johns Hopkins University Medical School,
Baltimore, MD.
Intravenous arginine butyrate has been shown to increase fetal hemoglobin
(HbF) in sickle cell and thalassemia patients. Recently, we observed that
sodium 4-phenylbutyrate, a drug administered orally to treat urea cycle
disorders, increases HbF production in nonanemic children and adults. We
treated six subjects with sickle cell disease over a period of 14 to 179
days. All subjects received their initial therapy of 9 to 13 g/m2/day as
0.5-g tablets of sodium 4-phenylbutyrate as inpatients. All subjects showed
a rapid increase in the percentage of F-reticulocytes (pretreatment, 1% to
20%; posttreatment, 10% to 44%). Four subjects were treated only 11 to 25
days as inpatients. Two of these four subjects failed to respond to the
outpatient component because of their inability to maintain an intake of 30
to 40 tablets per day. One subject (C) developed a rash at day 10 and
discontinued treatment at day 14. Another subject (B) was transfused for a
painful crisis on day 25. Subject A, treated for 179 days, has an increased
percentage of F cells, from 54% to 77%, and increased HbF levels, from
10.6% to 18%. Subject F, treated for 154 days, has an increased percentage
of F cells, from 59% to 73%, and an increased percentage of HbF, from 10.4%
to 16%. All subjects showed some increase in weight. Subject A developed
mild transient ankle edema. Myelotoxicity was not seen in any treated
patient. Oral administration of sodium 4- phenylbutyrate rapidly increases
F-cell production in sickle cell disease.
Volume 84,
Issue 1,
pp. 339-343,
07/01/1994
Copyright © 1994 by The American Society of Hematology
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