Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia

Michael R Debaun,William S Ball,Thomas H Howard,Paul Telfer ,Mark E Heiny,Natalia Dixon,Jason Fixler ,Gladstone Airewele,Julie A Panepinto,Michael A Kraut,Melanie Kirby‐Allen ,Emily Riehm Meier ,Suvankar Majumdar,Janet L Kwiatkowski,Brian Berman,Fenella J Kirkham,Gerald M Woods,Allison A King,Timothy L Mccavit,J Phillip Miller ,Rupa Redding‐Lallinger ,Baba Inusa ,Robert C Mckinstry,Annie Kamdem,Deborah Hirtz,Michael J Noetzel,Desirée A White ,Harold P Lehmann ,Corina E Gonzalez,Melissa Rhodes ,Mae O Gordon ,Charles T Quinn,Alexis A Thompson,Karen Kalinyak ,John J Strouse,Beng Fuh ,Sharada A Sarnaik,James F Casella

doi:10.1056/nejmoa1401731

Abstract

BackgroundSilent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.MethodsIn this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct.ResultsA total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04).ConclusionsRegular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.)

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