Trials Establish an Alternative to Blood Transfusions for Some Sickle Cell Patients
By Lindy Keane Carter
The drug hydroxycarbamide (hydroxyurea) has been proven to be as effective as blood transfusions in maintaining cranial blood flow velocities in some children with sickle cell disease (SCD) according to a national study. The TWiTCH trial (TCD With Transfusions Changing to Hydroxyurea), which included MUSC among its 26 trial centers, was designed to establish non-inferiority of the drug. The trial did so within four years, so TWiTCH was stopped one year early. The study’s findings were reported in The Lancet(February 13, 2016).
Sherron M. Jackson, M.D., Associate Professor of Pediatrics, Division of Pediatric Hematology/Oncology, was the Principal Investigator at the MUSC site. “Now we have something better than transfusions to minimize the risk of stroke,” she says. Chronic blood transfusions—the traditional therapy for preventing strokes – have significant negative side effects, including iron overload that can damage organs and lead to death. Hydroxyurea is easily administered in liquid or pill form.
Co-Principal Investigator of the national study was Robert J. Adams, M.D., Professor of Neurology at MUSC Health. “The TWiTCH study is very significant,” he says. “It gives us the second component of an effective protocol. The protocol of transcranial Doppler risk stratification of patients followed by regular red blood cell transfusion and then moving certain patients on to hydroxyurea should make long-term stroke prevention more practical. We hope this will lead to wider adoption of the protocol and bring us closer to the goal of a stroke-free generation of SCD patients.”
Decades ago, Adams led a group of scientists and technicians in adapting the then-new technology transcranial Doppler (TCD) to use in SCD and they showed how it can help prevent stroke. TCD measures blood flow velocity in cranial vessels. A high-flow velocity indicates that the sickle cells have begun to occlude the vessels, eventually causing ischemic stroke. Today, TCD is the chief diagnostic tool for identifying children at risk for stroke.
Annual TCD screening is recommended for children with SCD and is performed at South Carolina’s comprehensive sickle cell centers in Columbia, Greenville, and Charleston (MUSC Health). If the patient’s cranial flow velocity is abnormal, hematologists will consider hydroxyurea as a treatment option. Hydroxyurea increases production of fetal hemoglobin and, as a result, fewer sickle cells are produced. Approximately 100 babies with SCD are born each year in South Carolina, says Jackson. The peak age for strokes is eight years of age.
To eliminate strokes altogether, there is much work to be done. Adams says that there are three problems yet to address: TCD does not completely predict all ischemic strokes in children; there is no way to identify those destined to experience intracranial hemorrhages so that physicians may intervene; and there is no good strategy for stroke prevention after childhood. Further research is needed to better understand how to move medicine closer to reducing stroke or even eliminating it in these young patients.