血液病与血栓栓塞疾病杂志
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Intermittent Pulse Therapy with Arginine Butyrate for Sustained Fetal Hemoglobin Elevation in Sickle Cell Disease: Mini Review

John W.G. Addy*

Elevated Fetal Hemoglobin (Hb F) levels offer protection against various complications of sickle cell disease, enhancing overall survival. Past studies revealed that butyrate and short-chain fatty acids could boost Hb F production in erythroid cells in vitro and in vivo animal models. However, the known antiproliferative effects of butyrates on cell types, including erythroid cells, raised concerns about sustained Hb F response. To address this, we proposed an intermittent pulse therapy regimen, administering butyrate for 4 days followed by 10 to 24 days without exposure. This approach induced fetal globin gene expression in 9 out of 11 patients, resulting in a substantial and sustained increase in Hb F levels from 7.2% to 21.0% over an average duration of 29.9 weeks. The rise in Hb F correlated with increased F cells and F reticulocytes, accompanied by a significant elevation in total hemoglobin levels from 7.8 g/dL to 8.8 g/dL. This promising regimen, well tolerated and devoid of adverse effects, demonstrated marked and enduring Hb F improvement in over two thirds of enrolled adult sickle cell patients. However, further verification and extensive evaluation of clinical outcomes in a larger patient cohort are imperative to establish the efficacy of this approach.