For high-risk children with sickle cell anemia, hydroxyurea proves an effective option

By John Murphy, MDLinx
Published December 10, 2015

Key Takeaways

In children with sickle cell disease who are at high risk for stroke, hydroxyurea is as effective as blood transfusions to reduce blood flow velocities in the brain—a key risk factor for stroke—according to a study published online December 6, 2015 in The Lancet.

In this phase 3 trial—the Transcranial Doppler with Transfusions Changing to Hydroxyurea (TWiTCH) study—researchers used transcranial doppler (TCD) ultrasound to measure the velocity of blood flow to the brain. Children with the highest TCD velocities have a greater risk for stroke. The researchers found that hydroxyurea (currently the only FDA-approved drug for sickle cell disease) reduces TCD blood velocities to a similar degree as blood transfusions.

The sponsor of the study, the National Heart, Lung, and Blood Institute (NHLBI), called an early halt to the trial in November 2014 when positive interim results reached this primary endpoint.

At the initiation of the study, researchers at 26 pediatric hospitals and health centers in the United States and Canada enrolled 121 children (ages 4-16) who had abnormal TCD flow velocities (≥200 cm/s). The researchers randomized the children into two groups: one that received transfusions and one that was transitioned from transfusions to daily doses of hydroxyurea (oral hydroxycarbamide) starting at 20 mg/kg per day, and escalated to each participant's maximum tolerated dose. 

After analyzing the results, the study authors concluded that hydroxyurea can be as effective as transfusions at reducing stroke risk in these children.

“We wanted to provide the medical community with another way to help treat children who are at the greatest risk of stroke,” said co-principal investigator Russell Ware, MD, PhD, Director of the Division of Hematology at Cincinnati Children’s Hospital, in Cincinnati, OH.

“While blood transfusions are an effective option, there are questions about the long-term consequences of regular transfusions," he added. "Now families and health care providers have an additional treatment option with hydroxyurea.”

One of those consequences is that children who receive regular blood transfusions must also undergo chelation therapy to avoid the danger of iron overload.

“No child should ever have to face the prospect of suffering through a stroke,” said Gary H. Gibbons, MD, Director of the NHLBI. “Our institute is striving to achieve a stroke-free generation of children living with sickle cell disease. Studies like this are vital for moving us toward this worthwhile goal.”

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