Baylor College of Medicine

Ongoing research validates safety, efficacy for use of sickle cell treatment for children

Glenna Picton


Houston, TX -

As researchers continue to study the use of hydroxyurea as a treatment for sickle cell disease, there is more evidence to validate that it is safe and effective for children with the disease, said an expert pediatric hematologist from Baylor College of Medicine.

"We've known about this treatment since the 1960s," said Dr. Russell E. Ware, professor of pediatrics at BCM, director of the Texas Children's Center for Global Health and director of the Texas Children's Hematology Center. "It was at one time part of early HIV/AIDS treatment regimens, as well as a treatment for some types of cancer. In the last 20 years, we've been using it primarily as a treatment for sickle cell disease."

The treatment works by stimulating production of a form of hemoglobin present in the fetus and small infants that has the ability to block the sickling action of red blood cells.

It was approved by the United States Food and Drug Administration in 1998 as a treatment for sickle cell disease in adults, but is not yet approved for use in children.

Ware has been involved in many of the early clinical studies of the treatment and continues to be involved particularly its safety and efficacy for use in children. He discussed two of those recent studies.


Hydroxyurea safe in very young children


In May 2011, Ware, along with researchers from St. Jude Children's Research Hospital in Memphis, Tenn. (where he was chair of the Department of Hematology prior to joining BCM and Texas Children's Hospital), published new safety data on using the treatment in very young children (ages 9 to 18 months).

The randomized trial included 13 national centers and took place between October 2003 and September 2009. Half of the children with sickle cell disease were given hydroxyurea and the other half were given a placebo.

The researchers found that the children who were given hydroxyurea had much less pain, had fewer hospital visits and fewer transfusions. Perhaps more importantly, the drug appears to be safe even in these very young children. The results were recently published in the journal Lancet.

"This was a very long and complicated study that really opened the doors for us to use hydroxyurea more liberally," said Ware.


Proper dosing for children


Another important study Ware led recently uncovered new information about proper dosing in children.

In the study published online in August 2011 in the journal Blood, Ware and his team looked at why some children respond better to hydroxyurea than others.

Ware and his team conducted a detailed pharmacokinetics study (this is the branch of pharmacology concerned with the movement of drugs within the body).

Children with sickle cell disease were given hydroxyurea and then their blood was analyzed to assess their response or production of fetal hemoglobin.

"We observed a lot of differences in how children absorb and metabolize this drug," said Ware. "We suspect there are genetic reasons for these differences, which means some children may require different doses than others."

The study highlights another important step in researching this drug in children, Ware said. "We need to be able to accurately predict treatment responses for sickle cell disease, so we can give proper guidance to young patients and their families."


Future studies


Ware and his team are also currently leading a National Institutes of Health/National Heart, Lung, and Blood Institute trial that focuses on children with sickle cell disease who have a high risk of stroke.

Stroke becomes a risk because of the lack of blood flow to the brain, Ware said. "These children are identified as having an abnormal transcranial Doppler, or TCD, through periodic ultrasound exams," said Ware.

Called the TWiTCH trial (TCD With Transfusions Changing to Hydroxyurea), the trial will determine whether using hydroxyurea is a better alternative to using blood transfusion as a way to prevent strokes.

Blood transfusions have many side effects, including iron overload and the risks of developing antibodies or getting an infection, Ware said.

Ware serves at the national principal investigator on this trial. It will involve more than 25 institutions across the country and Canada.

Ware's group also is leading a new study of hydroxyurea in young patients with a lower risk of stroke, called Sparing Conversion to Abnormal TCD Elevation (SCATE). This trial has not yet begun enrollment, but will include sickle cell centers in Jamaica and Brazil.

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