Stroke With Transfusions Changing to Hydroxyurea

Inclusion Criteria: Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSOArab) Age range of 5.0-18.9 years, inclusive, at the time of study entry Initial (primary) completed overt clinical stroke after the age of one year (12 months) with documented infarction on brain computed tomography (CT) or magnetic resonance imaging (MRI) At least 18 months of chronic monthly erythrocyte transfusions since primary stroke Transfusional iron overload, defined as a previously documented liver iron concentration (LIC) greater than or equal to 5.0 mg Fe per gram of dry weight liver or serum ferritin greater than or equal to 500 ng/mL on two independent measurements Adequate monthly erythrocyte transfusions with average HbS less than or equal to 45% (the upper limit of the established academic community standard) in the 6 months prior to study entry Parent or guardian willing and able to provide informed consent with verbal or written assent from the child (less than 18 years of age) or subject willing and able to provide informed consent (older than 18 years of age) Ability to comply with study-related treatments, evaluations, and follow-up Exclusion Criteria: Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due to any of the following: Multiple RBC alloantibodies making cross-matching difficult or impossible RBC autoantibodies making cross-matching difficult or impossible Religious objection to transfusions that preclude their chronic use Non-compliance with transfusions in the 6 months prior to study entry (temporary exclusion) Inability to take or tolerate daily oral hydroxyurea, due to any of the following: Known allergy to hydroxyurea therapy HIV infection Cancer Pregnant or breastfeeding Previous stem cell transplant or other myelosuppressive therapy Clinical and laboratory evidence of hypersplenism, due to any of the following: Palpable splenomegaly greater than 5 cm below the left costal margin and Transfusion requirement greater than 250 mL/kg in the 12 months prior to study entry Abnormal laboratory values at initial evaluation (temporary exclusion): Pre-transfusion hemoglobin concentration less than 7.0 gm/dL White blood cell (WBC) count less than 3.0 x 109/L Absolute neutrophil count (ANC) less than 1.5 x 109/L Platelet count less than 100 x 109/L Serum creatinine more than twice the upper limit for age OR greater than or equal to 1.0 mg/dL Current participation in other therapeutic clinical trials Current use of other therapeutic agents for SCA (e.g., arginine, decitabine, magnesium) Any condition or chronic illness, such as a positive tuberculin (PPD) test, which in the opinion of the study physician makes study participation ill-advised Inability or unwillingness to complete required screening studies, including blood tests, brain MRI/magnetic resonance angiography (MRA), and liver biopsy A sibling enrolled in SWiTCH