Realizing Effectiveness Across Continents With Hydroxyurea

Inclusion Criteria 1. Pediatric patients with documented sickle cell anemia (typically HbSS supported by hemoglobin electrophoresis, complete blood count, and peripheral blood smear) 2. In the Original Cohort, age range of 1.00-9.99 years, inclusive, at the time of enrollment (now age 5.5 - 17.5 years); age range 3.0-10.0 years for the New Cohort 3. Weight at least 10.0 kg at the time of enrollment 4. Parent or guardian willing and able to provide written informed consent, with child's verbal assent as per local IRB/Ethics Board requirements 5. Willingness to comply with all study-related treatments, evaluations, and follow-up Exclusion Criteria 1. Known medical condition making participation ill-advised (e.g., acute or chronic infectious disease, HIV, or malignancy) 2. Acute or chronic severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or height for age \>3 z-scores below the median WHO growth standards. 3. Pre-existing severe hematological toxicity (temporary exclusions) 1. Anemia: Hb \<4.0 g/dL 2. Anemia: Hb \<6.0 g/dL with ARC \<100 x 109/L 3. Reticulocytopenia: ARC \<80 x 109/L with Hb \<7.0 g/dL 4. Thrombocytopenia: Platelets \<80 x 109/L 5. Neutropenia: ANC \<1.0 x 109/L 4. Blood transfusion within 60 days before enrollment (temporary exclusion) 5. In the Original Cohort, hydroxyurea use within 6 months before enrollment (temporary exclusion). In the New Cohort, the children should be hydroxyurea naïve, without any prior treatment exposure.