Research data indicate change in treatment

The agency issued a clinical alert to U.S. physicians who treat children with sickle cell anemia to advise them of the new data from the ãStroke Prevention Trial in Sickle Cell Anemiaä (STOP). The data shows that administering blood transfusions every three-to-four weeks to children with sickle cell anemia who are at high risk for stroke reduces their rate of stroke by 90 percent. The results were so compelling that the study was stopped on Aug. 29÷16 months earlier than planned. This will enable all children with sickle cell anemia to benefit from the new information.

ãThis is one of the most important and profound advances in the treatment of children with sickle cell anemia,ä said Dr. Miguel Abboud, who served as principal investigator for the MUSC part of the trial. ãWe have been able to predict which children are at risk for stroke and actually prevent strokes in these children through transfusion therapy.ä

MUSC was one of 14 centers in the United States and Canada to participate in the study, with Abboud and Dr. Sherron Jackson enrolling 11 of their patients into the national study protocol. Nationally, a total of 130 children (including the 11 at MUSC) with sickle cell anemia who were found to be at high risk of stroke were recruited for the study. The children were ages 2-16. Sixty-three children (six at MUSC) received blood transfusions every three-to-four weeks to keep the amount of abnormal or sickle hemoglobin in their blood to no more than 30 percent of total hemoglobin. The other 67 children received standard supportive care for sickle cell anemia.

After one year, the rate of strokes in the group treated with transfusion was 90 percent less than that of the standard care group. Ten children of the 67 in the standard care group had strokes, and only one child of the 63 in the transfusion group had a stroke At MUSC, none of the six children who received blood transfusions had a stroke, and three of the five in the standard care group had strokes.

The difference was considered significant enough to establish that the treatment should be considered for all children with sickle cell anemia who are at high risk for stroke.

Prior to the formal announcement of study findings, Abboud met with the families participating at MUSC to advise them of the results. Both Abboud and Jackson praised and thanked the participants and their parents, saying they have made a major contribution to benefit all children with sickle cell disease. ãIt was a privilege to work with these families,ä said Jackson.

ãThis was not easy,ä said Abboud. ãFirst these parents had their children identified as being at high risk for stroke, then some were randomly put in a protocol where they are given regular blood transfusions that have significant side effects, but may prevent strokes. Others were put in a group where they receive no more than standard therapy.ä These families have stayed with the study, and have come in regularly for treatment and observations. ãMy heart goes out to those children in the standard therapy who had strokes.ä Abboud said. Now that the results are in, all children will have the opportunity to be screened, and those found at risk can be offered transfusion therapy.

Transcranial doppler (TCD) screening was used to identify children at risk for stroke for the study. This is an ultrasound technique that measures the velocity of blood flow in the brain. High blood flow velocities in one or more major arteries of the brain are thought to indicate a significant narrowing in key blood vessels supplying the brain, which markedly increases the risk of a stroke. The TCD instrument for the study has been used for years to screen adults for increased risk of stroke and was adapted for use in children with sickle cell disease by Dr. Robert Adams, principal investigator of STOP and professor of neurology at the Medical College of Georgia.

The children in the transfusion group were monitored for transfusion-associated complications. At this point, there is no evidence that any of them contracted a transfusion-transmitted virus during the study, but nine patients developed antibodies to proteins in the blood, which complicates the task of finding matching blood for future transfusions. Most of the children also developed excess levels of iron, which can be harmful to several vital organs and must be treated with a procedure called chelation therapy. This is a painful, inconvenient, and expensive process involving ongoing subcutaneous infusions of a drug that removes the iron. Children with sickle cell anemia who receive transfusion therapy to prevent strokes will probably require long-term chelation therapy.

But Abboud and Jackson emphasize that despite this, the benefit of preventing strokes and their debilitating effects, both physical and intellectual, far outweigh the risk associated with repeated transfusion.