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STOP Trials Demonstrated Value of Chronic Blood Transfusion to Prevent Stroke in Children With Sickle Cell Disease

By Bruce Wilson

PENNSYLVANIA, PA -- September 12, 2006 -- The results of 2 landmark trials provide substantial scientific support for the use of transcranial Doppler ultrasound (TCD) screening to prevent stroke in children with sickle cell disease (SCD), said experts at a recent independent sickle cell disease meeting.

The trials -- Stroke Prevention in Sickle Cell Anemia (STOP) and STOP 2 -- also provide evidence to support the use of regular blood transfusions in children who are at high risk for stroke and of continued transfusions while on treatment or intense surveillance with TCD during transfusion withdrawal.

Stroke is a common complication in children with sickle cell disease (SCD), resulting in substantial rates of death and neurocognitive sequelae. Without treatment, two thirds of SCD patients will have stroke recurrence, most often within 3 years, leading to even worse outcomes, explained Janet Kwiatkowski, MD, associate professor of pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

Transcranial Doppler ultrasonography (TCD) can estimate the risk of stroke based on blood flow velocity in the proximal large intracranial arteries. For example, a velocity of 200 cm/sec or greater indicates high risk, whereas less than 170 cm/sec is considered normal.

Chronic blood transfusion is the treatment of choice for prevention of secondary stroke, reducing the risk from about 65% to 10%. However, it is not clear how well transfusions prevent recurrent hemorrhage.

The STOP study (Adams et al. N Engl J Med 1998;339:5-11) used TCD to assess the value of transfusions in preventing a first stroke among children with SCD (n = 130) and no history of stroke but with a TCD indicating a high risk of stroke. Subjects were randomized to receive standard care or transfusions to reduce the hemoglobin S concentrations to less than 30% of the total hemoglobin concentration.

Results showed that children who received transfusions had a reduction in the risk of first stroke by 92% (P < .001). This result was greater than the researchers had projected, according to Dr. Kwiatkowski. However, she added, TCD was not found to be useful for predicting stroke in this study.

The STOP 2 trial (Adams et al. N Engl J Med 2005;353:2769-78) was conducted to determine how long transfusion therapy should be continued in patients with SCD. This study enrolled 79 children with SCD who were at high risk of stroke and had received transfusions for at least 30 months, during which their TCD readings became normal.

Subjects in STOP 2 were randomized to receive continued transfusions or to stop their transfusions. Among the 41 children in the transfusion-halted group, 14 developed high-risk Doppler readings and 2 had a stroke within 4.5 months (2.1 to 10.1) of the last transfusion. No events occurred in the 38 children who continued to receive transfusions.

Since the publication of the STOP results, the rate of first-episode stroke admission in SCD patients has declined significantly, Dr. Kwiatkowski said. A study conducted in California showed that admissions per 100 person-years decreased from 0.88 in 1998 to 0.50 in 1999 and down again to 0.17 in 2000 (Fullerton et al. Blood 2004;104:336-339).

"This doesn't show who was screened or not, but it shows that in the time period when STOP results became available, there was a decline in the rate of strokes, at least in California, suggesting that perhaps the screening and the transfusion therapy was reducing the stroke risk overall," Dr. Kwiatkowski said.


[Presentation title: STOP and STOP 2 Results.]

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