Experimental Drug Therapy to Increase Fetal Hemoglobin
The amount of fetal hemoglobin within each red cell plays a major role in determining the severity of thalassemia. The increase in gamma globin chain synthesis decreases the alpha chain imbalance and improves the anemia. Multiple drugs have been studied to increase hemoglobin F. Histone deacetylase (HDAC) inhibitors such as butyrate and short-chain fatty acids have had benefit in select patients, but most responses have been modest and unpredictable. New HDAC drugs are under study. The first successful drug therapy for fetal hemoglobin in thalassemia was 5-azacytidine. This was abandoned because of toxicity. Recent pilot studies evaluating a safer analog (decitabine) are ongoing; however, the long-term benefit and toxicity are unknown. Erythropoietin has increased fetal hemoglobin and total hemoglobin, particularly in patients with relatively low levels of erythropoietin. However, the long-term benefit is unknown, and the risk of marrow expansion is a cause for concern.