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Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a
clinical trial
AF Collins, HA Pearson, P Giardina, KT McDonagh, SW Brusilow and GJ Dover
Johns Hopkins University School of Medicine, Baltimore, MD.
Butyrate analogues have been shown to increase fetal hemoglobin (HbF)
production in vitro and in vivo. Sodium phenylbutyrate (SPB), an oral agent
used to treat individuals with urea-cycle disorders, has been shown to
increase HbF in nonanemic individuals and in individuals with sickle cell
disease. We have treated eleven patients with homozygous beta thalassemia
(three transfusion dependent) and one sickle-beta- thalassemia patient with
20 g/d (forty 500-mg tablets) of SPB for 41 to 460 days. All patients
showed an increase in the percent of F reticulocytes associated with
treatment, but only four patients responded by increasing their Hb levels
by greater than 1 g/dL (mean increase, 2.1 g/dL; range, 1.2 to 2.8 g/dL).
None of the transfusion- dependent thalassemia subjects responded. Increase
in Hb was associated with an increase in red blood cell number (mean
increase, 0.62 x 10(12)/L), and mean corpuscular volume (mean increase, 6
fL). Changes in percent HbF, absolute HbF levels, or alpha- to
non-alpha-globin ratios as measured by levels of mRNA and globin protein in
peripheral blood did not correlate with response to treatment. Response to
treatment was not associated with the type of beta-globin mutation, but
baseline erythropoietin levels of greater than 120 mU/mL was seen in all
responders and only two of eight nonresponders to SPB. Compliance with
treatment was greater than 90% as measured by pill counts. Side effects of
the drug included weight gain and/or edema caused by increase salt load in
2/12, transient epigastric discomfort in 7/12, and abnormal body odor in
3/12 subjects. Two splenectomized patients who were not on prophylactic
antibiotics developed sepsis while on treatment. We conclude that SPB
increases Hb in some patients with thalassemia, but the precise mechanism
of action is unknown.
Volume 85,
Issue 1,
pp. 43-49,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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