NHLBI Stops the STOP II Trial Early

As previewed in yesterday’s edition of ASH News Daily, the results of the Stroke Prevention Trial II (STOP II) were presented by Dr. Robert Adams as a special “late-breaking” announcement following the Plenary Scientific Session yesterday afternoon. STOP II, which was initiated in 2000, was to enroll 100 patients ages two to 18 over six years. The study was halted by the NHLBI on November 10th (two years early) with 79 patients enrolled. The question being asked was whether children with sickle cell anemia at high risk for stroke could at some point after a minimum of 30 months (range 30-91 months) safely stop receiving the periodic blood transfusions that prevent strokes. When the decision was made to halt the trial early, 14 of the 41 patients who had been randomly assigned to stop transfusions reverted to high risk of stroke as measured by a special ultrasound technique, and, unfortunately, two patients suffered a stroke. There were no strokes or reversions to high stroke risk in the group that continued with transfusions. The NHLBI is issuing a clinical alert of the study’s results to inform and advise physicians who treat children with sickle cell anemia that stopping transfusions cannot be recommended. “This important study shows the value of continuing periodic blood transfusions in preventing the serious and debilitating consequences of stroke,” said NHLBI Acting Director Barbara Alving, M.D. “At the same time, there are risks of chronic transfusions and the decision to continue with this treatment must be made on a case-by-case basis,” she added.

About 10 percent of sickle cell patients are at risk for stroke. Twenty percent of patients are at risk for “silent cerebral infarcts,” small strokes that can interfere with cognitive functioning and school performance because brain tissue is damaged. The importance of transfusion therapy in preventing strokes in patients with sickle cell anemia was established in 1997 when the results of the Stroke Prevention Trial in Sickle Cell Anemia (STOP I) were released in a clinical alert. STOP I found that administering blood transfusions every three to four weeks to sickle cell anemia children who are at high risk for stroke reduces their rate of first-time stroke by 90 percent.

“STOP I showed that we could prevent stroke and its debilitating consequences, including brain damage. What we didn’t know was whether the transfusions could be safely stopped at some point. This was an important question because there are some problems with blood transfusions, including increased risk of iron overload,” said Robert Adams, M.D., principal investigator of both STOP I and STOP II and Regents Professor of Neurology and Professor of Pediatrics, Medical College of Georgia. “Now we know that for high-risk patients, it is not safe to stop transfusions even if the transcranial Doppler (TCD) has returned to normal range. We need to weigh carefully the risks of this preventive therapy and make sure we monitor patients closely with TCD. We also need to come up with a better way to maintain the stroke prevention benefit while lowering the side effects of transfusion treatment,” added Dr. Adams.

A final note of emphasis is that the patients studied in STOP II were those with TCD velocities that reverted to low risk on periodic transfusions, and without severe arterial lesions on magnetic resonance angiography (MRA). This subset of children who participated in STOP II are thought to be at lower risk for stroke than those children who had been in STOP I but did not qualify for STOP II because their TCD velocities did not revert to normal on transfusions, or because they had arterial lesions on MRA.