Study shows sickle cell anemia drug is safe, effective for infants and toddlers

A drug long used for adults with sickle cell disease could change how the disease is managed in very young children.

In what is being hailed as a significant advance in the treatment of children with sickle cell anemia, a drug commonly used to treat adults has been shown to be safe and effective in children. A multi-site, placebo-controlled study, conducted in part at the University of Alabama at Birmingham and the Children’s Hospital of Alabama, showed that hydroxyurea reduced episodes of pain and pneumonia in infants and toddlers with sickle-cell disease and reduced hospitalizations and blood transfusions.

bob_blood_2_siteThe findings, published in the May 14, 2011, issue of the journal The Lancet, are the result of a six-year, 13-site study of nearly 200 infants and toddlers ages 9-18 months with sickle-cell disease.

“This is the first placebo controlled, large-scale study of hydroxyurea for children ever conducted, and the study focuses uniquely on the drug’s use in preventing sickle-cell complications in infants with the disease,” said Thomas Howard, M.D., a professor of hematology/oncology and principal investigator for the UAB study, who is a practicing physician at Children’s Hospital. “These findings show hydroxyurea potentially can improve the lives of the next generation of patients and likely will change how we treat sickle cell in very young children.”

The study authors suggest that hydroxyurea should be considered for all infants and toddlers with sickle cell in hopes of preventing or delaying complications from the disease. Howard says the study’s findings are highly important for patient care although more study still may be needed to determine optimal guidelines for its use in young children and to dispel any concerns regarding long term side-effects of hydroxyurea.

Sickle cell is the result of a gene mutation that causes red blood cells to produce sickle hemoglobin, which forces red cells to take on a stiff, inflexible crescent shape. The crescent cells can clog blood vessels triggering painful episodes, pneumonia, central nervous system damage, strokes and even kidney failure.

For a few months after birth newborns with sickle cell continue to produce fetal hemoglobin, which does not cause red blood cells to assume the crescent shape. But after birth, production of fetal hemoglobin decreases and sickle hemoglobin increases, causing disease symptoms to appear. Hydroxyurea increases production of non-sickling fetal hemoglobin, which moderates the severity of sickle-cell symptoms.

An analysis of 179 patients who completed at least 18 months of the study revealed children in the placebo group, those not receiving hydroxyurea, had nearly twice as many acute pain episodes, were three times more likely to suffer a pneumonia-like illness known as acute chest syndrome and five times more likely to develop painful swelling of the hands and feet called dactylitis. They also were slightly more likely to be hospitalized or need a blood transfusion to ease sickle-cell symptoms.

The most common side-effect reported in this study was a mild to moderate drop in the neutrophil type of white blood cells. Low neutrophil counts can be associated with an increased risk of infection, but there was no evidence of increased infections in study participants. A follow-up study is now under way to check for possible long-term benefits from continued treatment with higher doses of hydroxyurea.

Researchers at St. Jude Children’s Research Hospital in Memphis led the Pediatric Hydroxyurea Phase III clinical trial, referred to as the Baby HUG trial. The study was funded by the National Heart, Lung and Blood Institute, one of the National Institutes of Health.

Sickle-cell anemia is the most common genetic disorder affecting Americans of African descent and strikes persons of other racial and ethnic backgrounds.