Optimizing Hydroxyurea Therapy in Children With Sickle Cell Anemia In Malaria Endemic Areas: The NOHARM Maximum Tolerated Dose (MTD) Study
NOHARM MTD is an extension of a previous study for children with Sickle Cell Anemia (SCA) who were enrolled in the NOHARM study. All children enrolled in NOHARM received hydroxyurea treatment at a fixed daily dose of 20 mg/kg/day. This dose was selected as a likely safe dose, but does not escalate hydroxyurea to maximum tolerated dose MTD as is commonly done in the US. Without this information, we cannot know whether hydroxyurea treatment at the MTD would be feasible (since it requires closer monitoring to avoid hematological toxicities), safe (since adverse events may be greater with MTD, risk of malaria may be altered by MTD, and risk of infections as a result of neutropenia could also be greater with MTD) or beneficial (MTD is associated with higher hemoglobin and fetal hemoglobin concentration).
• Adolescents with confirmed SCA who are currently enrolled in the NOHARM MTD Study of hydroxyurea at the Mulago Hospital Sickle Cell Clinic (MHSCC), will be eligible for the NOHARM MTD LT version 2.0 extension study after completing re-consent. An age-matched untreated (hydroxyurea-naïve) group of adolescents will also be enrolled as a Comparator Cohort. This will comprise 75 children from Kampala and surrounding districts, ages 11 - 18 years of age, with confirmed SCA.