Abstract
Children with sickle cell anemia (SCA) have poor growth and pubertal development. REACH (Realizing Effectiveness Across Continents with Hydroxyurea) is a prospective trial evaluating the feasibility, safety, and benefits of hydroxyurea at maximum tolerated dose (MTD) for children with SCA in sub-Saharan Africa. Children aged 1 to 10 years received open-label hydroxyurea with longitudinal follow-up. Height, weight, and pubertal staging were collected over 7 years of treatment. Biomarkers included insulin-like growth factor I (IGF-I), IGF-binding protein 3, luteinizing hormone, follicle-stimulating hormone, and anti-Mullerian hormone (AMH). Hydroxyurea commenced at an average (mean ± 1 standard deviation [SD]) age of 5.9 ± 2.4 years (range, 1.6-10.2) for girls (n = 296) and 5.4 ± 2.4 years (range, 1.3-10.1) for boys (n = 310). Using natural history SCA-specific reference curves, the mean weight-for-age z score improved from 0.47 ± 0.90 at enrollment to 0.69 ± 1.00 on hydroxyurea treatment. Height increased from 0.26 ± 0.90 to 0.42 ± 1.00 on treatment, and body mass index from 0.46 ± 1.00 to 0.85 ± 1.20. IGF-I remained low in many participants. Puberty was delayed in 25% to 30% of children, with gradual progress on treatment. AMH was low (<2.5th percentile) in 4% of girls, whereas 52% of boys had low AMH at baseline and 28% at follow-up. Long-term hydroxyurea treatment at MTD is associated with beneficial effects on growth with improved weight and height, and does not negatively affect pubertal developmenty in children with SCA in sub-Saharan Africa. This study was registered at www.clinicaltrials.gov initially as NCT01966731 and is now registered as NCT06171217 for long-term follow-up.