 | Battling Sickle Cell Disease
$18.5 million grant is most ever awarded to a WUSTL pediatrician
St. Louis, Oct. 29, 2003 — Children across the world with sickle cell disease will benefit from an $18.5 million grant awarded to researchers at Washington University School of Medicine in St. Louis to determine the effectiveness of blood transfusion therapy as a treatment for preventing silent strokes.
"Regardless of the outcome of the study, our results will change the standard of care for children with sickle cell disease throughout the world," says principal investigator Michael R. DeBaun, M.D., M.P.H., associate professor of pediatrics and of biostatistics at the School of Medicine and a pediatric hematologist at St. Louis Children’s Hospital. "At the end of the study, we will know whether blood transfusion therapy will prevent silent strokes in children with sickle cell disease.
"If there is a significant benefit, the standard of care will be changed for these vulnerable patients; and even if no benefit is detected, then patients will not be subject to unnecessary therapy."
The National Institutes of Health (NIH) grant — the most ever awarded to a pediatrician at Washington University School of Medicine — will fund a six and a half year international clinical trial at 22 sites, including ones in France, Canada and England. DeBaun and his staff will serve as the coordinating center for the international trial.
Silent strokes, which frequently go unrecognized, are one of the most serious afflictions associated with sickle cell disease. They can cause declines in school performance, increased forgetfulness and a diminished ability to follow even simple instructions.
DeBaun's preliminary research over the past decade reveals that silent strokes seriously affect children's educational attainment and can lead to further neurological damage. His team has recently completed a pilot trial showing that blood transfusion therapy is a safe and potentially effective therapy for children with silent strokes.
Sickle cell disease, an inherited disorder of the red blood cells, is the most common genetic disorder in African-Americans. The disease affects one in 400 African-American infants — and 20 percent of those children will suffer a silent stroke before they finish high school.
In sickle cell disease, red blood cells change to a curved, or sickle-shape, instead of the normal, round shape. Sickle cells become stuck in blood vessels, resulting in painful episodes.
In addition to pain, the most common afflictions associated with sickle cell disease are silent and overt strokes, kidney and spleen dysfunction, chronic anemia and increased risk of bacterial infection.
The only way to detect a silent stroke is to take pictures of the brain by using magnetic resonance imaging (MRI). Until now, there has been no systematic strategy to identify or treat children with silent strokes.
"It is crucial to identify children with silent strokes because kids who have them are at a 24 percent risk over the next three years for further silent or overt strokes, which may leave physical defects and/or greater cognitive deficits. What we do not know is whether the benefits outweigh the
risks of treatment,” DeBaun says.
The standard treatment for overt strokes in children with sickle cell disease is blood transfusion therapy. The NIH grant will allow DeBaun and his international team of researchers to investigate whether blood transfusion therapy will also prevent silent strokes.
For three years, DeBaun’s group will randomly allocate blood transfusion therapy to 50 percent of the study participants, and the other half will be observed.
"If blood transfusion therapy is effective, the magnitude of this benefit for children with silent strokes will be tremendous," DeBaun says.
The groundbreaking trial will enroll 1,880 children from around the world. All the children will have an MRI performed on their brains to detect silent strokes.
In addition, a blood sample will be collected to establish the world's largest DNA repository for children with sickle cell disease — which will allow future genetic research to explore the genetic basis for stroke and other sickle cell-related diseases.
Patients receiving the preventive blood transfusion therapy will be transfused at three-to-four week intervals to maintain near normal hemoglobin levels. MRIs will also be performed to detect new strokes and the progression of brain lesions at the beginning of the study, again at 12 months to 18 months and at the study's completion.
"We have a once in a lifetime opportunity to not only improve the quality of life for children currently afflicted with this disease," DeBaun says, "but to also change the understanding of the disease for future generations of children and the pediatricians who treat them."
Editor’s Note: Photo available of Dr. DeBaun and a young sickle cell patient. |