Bone marrow transplantation is usually entertained after stroke, but TCD and other indexes of cerebral vasculopathy have also been used as an indication for myeloablative stem- cell transplantation. One study of 55 patients with a median follow-up of 6 years found overall and event-free survival rates of 93% and 85%, respectively. No new ischemic lesions were reported, and TCD velocities decreased.590 In a study of 55 children who underwent bone marrow transplantation for severe SCD, 16 patients without prior stroke and unremark- able MRI before bone marrow transplantation had no clinical or silent stroke on follow-up, and the 10 patients with prior silent ischemia had no further events.591 Bone marrow trans- plantation is promising for primary stroke prevention but requires additional study. No trial has been done on the primary prevention of stroke in adults with SCD. Improvements in care have increased life expectancy in people with SCD, and it is anticipated that stroke prophylaxis in older patients with SCD will pose an increasing challenge in the future. SCD: Summary and Gaps Significant progress has been achieved in the primary pre- vention of stroke in children with SCD. TCD can be used to identify children who are at high risk of stroke and who benefit from transfusion therapy. Although the optimal screening interval has not been established, TCD remains the most extensively validated method for risk assessment. Improvements in prediction may come from incorporating additional predictors such as anterior cerebral artery velocity, blood biomarkers, variations in several genes, and nocturnal oxygen saturation. On the basis of STOP II, even those whose risk of stroke decreases with transfusion therapy on the basis of TCD criteria have an 50% probability of reverting to high risk or having a stroke if transfusion therapy is discontinued. 