Can a new combination treatment prevent a secondary stroke in children with sickle cell anemia?

St. Jude Children’s Research Hospital will lead a national Phase III clinical trial to investigate whether a new combination treatment can prevent a secondary stroke in children with sickle cell anemia (SCA) and eliminate the need for nightly injections with a drug that reduces iron overload in these patients.

The five-year study, called Stroke With Transfusions Changing to Hydroxyurea (SWiTCH), is supported by a grant of more than $18 million from the National Institutes of Health (National Heart, Lung, and Blood Institute) and includes 20 major pediatric sickle cell centers in addition to St. Jude. The study is now being organized and will enroll the first children in spring 2006. SCA is an inherited disease in which the oxygen-carrying protein in the red blood cells is abnormal, giving the red cells a twisted (sickled) shape that can disrupt circulation, leading to pain, stroke, and other disabling and sometimes fatal complications.

SWiTCH holds promise for greatly simplifying and improving the long-term care of children with the disease who have suffered strokes, according to Russell E. Ware, M.D., Ph.D., chief of the Hematology Division at St. Jude and principal investigator of the clinical trial. “Sickle cell anemia is a relentless disease that increasingly disables children as they grow,” Ware said. “In fact, children with stroke receive difficult treatments with their own complications that must be treated. There is reason to hope that SWiTCH could finally give us a better way to enhance the lives of these children, who suffer daily from their disease and face the threat of stroke and early death.”

The current treatment for children with SCA who have suffered strokes includes monthly blood transfusions to provide red cells that are not sickled. This ongoing treatment must later be combined with nightly injections of a drug (Desferal ®) that eliminates excessive iron buildup caused by regular blood transfusions. Excessive iron damages internal organs--a condition called hemochromatosis. The nightly injections of Desferal, an iron chelator, are painful and inconvenient, often prompting children to forego the injection, since iron buildup does not initially cause the child discomfort, but the injections always do. Chelators are molecules that bind to metals so they can be eliminated from the body.

The goal of SWiTCH is to compare patient outcomes using blood transfusions with outcomes using hydroxyurea. Hydroxyurea will not completely eliminate the sickled red cells, but it is expected to stimulate production of enough red cells carrying fetal hemoglobin to reduce SCA symptoms. The study will also compare the efficacy of daily at-home injections of Desferal with the less painful and more convenient monthly removal of blood (phlebotomy) at a medical facility. Half of the children in SWiTCH will remain on the standard treatment (transfusions and chelator) while the other half will be treated with the alternative treatment (hydroxyurea and phlebotomy).

The study will address a timely topic among physicians who treat children with SCA. Specifically, SWiTCH will include children who have already suffered one stroke and are at risk for additional strokes because of blood vessel damage in their brains.

“This is the first study to directly compare transfusions with hydroxyurea for the treatment of SCA,” Ware said. “If hydroxyurea can successfully substitute for transfusions in children who already have cerebrovascular disease and damage to their brains, we will be very interested in also seeing if the drug can prevent this process as well. That would spare children with SCA from suffering first strokes and greatly improve their lives.”