Real-world experience using hydroxyurea in children with sickle cell disease in Lilongwe, Malawi

Introduction: Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub-Saharan Africa (SSA). Historically, hydroxyurea administration in SSA has been restricted due to limited region-specific evidence for safety and efficacy. Methods: We conducted a prospective observational cohort study of pediatric patients with SCD in Malawi. From January 2015 to November 2017, hydroxyurea at doses of 10–20 mg/kg/day was administered to children with clinically severe disease (targeted use policy). From December 2017 to July 2018, hydroxyurea was prescribed to all patients (universal use policy). Results: Of 187 patients with SCD, seven (3.7%) died and 23 (12.3%) were lost to follow-up. The majority (135, 72.2%) were prescribed hydroxyurea, 59 (43.7%) under the targeted use policy and 76 (56.3%) under the universal use policy. There were no documented severe toxicities. Under the targeted use policy, children with SCD demonstrated absolute decreases in the rates of hospitalization (−4.1 per 1000 person-days; −7.2, −1.0; P =.004), fevers (−4.2 per 1000 person-days; −7.2, −1.1; P =.002), transfusions (−2.3 per 1000 person-days; 95% confidence interval: −4.9, 0.3; P =.06), and annual school absenteeism (−51.2 per person-year; −60.1, −42.3; P <.0001) within 6 months of hydroxyurea commencement. Conclusion: We successfully implemented universal administration of hydroxyurea to children with SCD at a tertiary hospital in Malawi. Similar to recently reported trials, hydroxyurea was safe and effective during routine programmatic experience, with clinical benefits particularly among high-risk children. This highlights the importance of continued widespread scale-up of hydroxyurea within SCD programs across SSA.