ORAL SODIUM PHENYLBUTYRATE THERAPY IN HOMOZYGOUS BETA-THALASSEMIA - A CLINICAL-TRIAL
ORAL SODIUM PHENYLBUTYRATE THERAPY IN HOMOZYGOUS BETA-THALASSEMIA - A CLINICAL-TRIAL
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DOI：
10.1182/blood.v85.1.43.bloodjournal85143
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发表时间：
1995-01-01
期刊：
影响因子：
20.3
通讯作者：
DOVER, GJ
中科院分区：
文献类型：
--
作者：
COLLINS, AF;PEARSON, HA;DOVER, GJ
丁酸盐类似物已显示在体外和体内增加胎儿血红蛋白（HbF）的产生。苯丁酸钠（SPB）是一种用于治疗尿素循环障碍的口服药物，已被证明可增加非贫血患者和镰状细胞病患者的HbF。我们用20 g/d（40片500 mg片剂）的SPB治疗了11例纯合子β地中海贫血患者（3例输血依赖性）和1例镰状β地中海贫血患者，持续41至460天。所有患者均显示与治疗相关的F网织红细胞百分比增加，但只有4例患者的Hb水平增加超过1 g/dL（平均增加2.1 g/dL;范围1.2 - 2.8 g/dL）。无输血依赖性地中海贫血受试者应答。Hb增加与红细胞数量（平均增加0.62 x 10（12）/L）和平均红细胞体积（平均增加6 fL）增加相关。通过外周血中mRNA和珠蛋白水平测量的百分比HbF、绝对HbF水平或α-与非α-珠蛋白比率的变化与治疗反应无关。对治疗的反应与β-珠蛋白突变的类型无关，但在所有SPB反应者中观察到基线促红细胞生成素水平大于120 mU/mL，而在8例SPB无反应者中仅观察到2例。按照药丸计数测量，治疗依从性大于90%。药物的副作用包括2/12例盐负荷增加引起的体重增加和/或水肿，7/12例一过性上腹部不适，3/12例异常体臭。两名脾切除患者在治疗期间未预防性使用抗生素，发生脓毒症。我们得出结论，SPB增加血红蛋白在某些地中海贫血患者，但确切的作用机制尚不清楚。(C)1995年，美国血液学会。
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 far 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. (C) 1995 by The American Society of Hematology.