Ten Years of Hydroxyurea for Ugandan Children with Sickle Cell Anemia

p o n d e n c e Ten Years of Hydroxyurea for Ugandan Children with Sickle Cell AnemiaTo the Editor: Sickle cell anemia is a severe inherited hemoglobinopathy with a large global burden, particularly in sub-Saharan Africa. 1 Hydroxyurea, which is standard therapy for sickle cell anemia in high-resource settings, has had encouraging short-term results in low-resource settings.2,3 However, long-term safety and benefits remain undefined in Africa, where malnutrition, malaria, and poor health care access confound outcomes.Here, we summarize the use of hydroxyurea treatment in young Ugandan children with sickle cell anemia in a series of three studies over a 10-year period.Starting in 2014, in the NOHARM (Novel Use of Hydroxyurea in an African Region with Malaria) study (NCT01976416), 207 children (mean age, 2.2 years) were randomly assigned to receive either hydroxyurea or placebo for 1 year, followed by open-label hydroxyurea for all the children.In the subsequent NOHARM MTD (Maximum Tolerated Dose) study (NCT03128515), 187 children underwent a second randomization to receive hydroxyurea at either a fixed dose or an escalated dose.For the past 6 years, in the extension study (NOHARM MTD LT [Long-Term]), 174 children (mean age, 12.8 years) have continued to receive hydroxyurea at the maximum tolerated dose, with total hydroxyurea exposure of 1861 years: 589 person-years in those who received a fixed dose and 1272 person-years in those who received the maximum tolerated dose, including 1070 personyears in the long-term extension.Across the 10year treatment period, the overall retention was 84% (174 of 207 children).Details regarding the enrollment and results in the individual studies are provided in the Supplementary Appendix and the protocol, both available with the full text of this letter at NEJM.org.