Treating babies who have sickle cell disease (SCD) with oral liquid hydroxyurea appears to prevent the onset of long-term complications triggered by this disease, according to results of a preliminary study by investigators at St. Jude Children's Research Hospital.
The study's findings are important because the onset of damage caused by SCD complications can occur as early as three months after birth. Starting treatment before those complications begin could dramatically reduce the chance of organ damage and premature death. A report on the study appears in the June 14 online edition of Blood.
In SCD, a genetic mutation causes oxygen-carrying protein hemoglobin (Hb) to form rigid cords in red blood cells, causing the cells to take on a bent, sickled shape. The sickled cells clog small blood vessels, causing pain and serious damage to the brain, kidneys, spleen and other organs; and the subsequent premature death of the abnormal red cells causes anemia. In the United States, SCD is found mostly among African Americans.
Hydroxyurea increases the production of fetal hemoglobin (HbF), the main oxygen transport protein in fetal red blood cells. Because HbF prevents red blood cells from "sickling," clinicians have used hydroxyurea for about a decade to reactivate HbF production in adults and older children with SCD. In addition, hydroxyurea reduces the severity of symptoms suffered by adolescents and adults with SCD, such as lung infections, organ damage, stunted growth, impaired brain development and acute chest syndrome (ACS). ACS refers to an infection in the lungs that causes difficulty breathing, pain and other symptoms and can be fatal.
The current St. Jude study was an extension of a previous clinical trial, Hydroxyurea Safety and Organ Toxicity (HUSOFT), which was the first in which young babies were treated with hydroxyurea. The original HUSOFT study, published in 2001, demonstrated that short-term oral liquid hydroxyurea therapy can be safe and effective in babies with SCA. In the extension study, these infants were followed for up to six years of therapy.
"Our results are promising and justify a larger multicenter clinical trial to confirm that treating babies with hydroxyurea is safe and effective," said Jane S. Hankins, M.D., a physician at the St. Jude Comprehensive Sickle Cell Center and the study's lead author. "If a larger trial supports our observations in the HUSOFT Extension, the treatment of sickle cell disease will undergo a significant change."
"This study is particularly encouraging because it suggests that we can treat babies with hydroxyurea for several years without side effects serious enough to limit the use of this drug," said Winfred Wang, M.D., St. Jude Comprehensive Sickle Cell Center director. "Our aim is to make sickle cell anemia a survivable disease that doesn't significantly reduce a person's quality of life." Wang is the senior author of the paper in Blood.
A two-year pilot study of 21 babies with SCD, the original HUSOFT was designed to examine the feasibility of treating infants with liquid hydroxyurea; to determine the toxicity of this drug in babies; to assess hydroxyurea's effects on fetal Hb levels; and to observe if this treatment could preserve spleen function. Patients received 20 milligrams/kilgrams of body weight/day (mg/kg/day) of hydroxyurea. All 21 patients who completed the initial study were enrolled by their parents into the HUSOFT Extension study. In that study, the dose of hydroxyurea was elevated from 20 to 30 mg/kg/day for an average of 4.0 years (range 2.1 – 6.0 years).