The GLOBE Trial: Efficacy and Safety of L-Glutamine Plus Hydroxyurea Versus Hydroxyurea Alone in Sickle Cell Anemia – A Double-Blind, Randomized Study

Objective: Hydroxyurea (HU) reduces complications of sickle cell anemia (SCA), but the response is variable. L-glutamine, an antioxidant that improves redox balance, is implicated in a distinct pathophysiological pathway and may provide additional clinical benefit when added to HU. We evaluated HU plus L-glutamine versus HU alone in pediatric/adolescent SCA. Materials and Methods: -thalassemia were randomized to the HU + L-glutamine (n=27) or the HU + placebo (n=26) group while continuing HU at ~20 mg/kg/day. The primary endpoint was vaso-occlusive crisis (VOC) frequency; secondary endpoints included acute chest syndrome (ACS), hospitalizations, and hematological parameters. Analyses were performed for intention-totreat with baseline-adjusted models for key outcomes. Results: Over 6 months, the HU + L-glutamine group experienced significantly fewer VOCs (1.00±0.73 vs. 1.65±0.80; p=0.003) and ACS episodes (0.19 vs. 0.77; p=0.006). Hospitalizations declined by 40% (p=0.04). Hemoglobin (Hb) rose more in the combination arm (+0.78 vs. +0.32 g/dL; p=0.028), with larger reductions in reticulocytes (p=0.04) and greater fetal Hb increases (+6.2% vs. +1.6%; p