Non-pharmacological interventions as adjuncts to iron chelation therapy in sickle cell disease on chronic transfusion: a scoping review with evidence gap mapping

Iron overload is a significant complication for patients with sickle cell disease (SCD) on chronic red blood cell (RBC) transfusion therapy. While pharmacological iron chelation therapy (ICT) is the standard of care, it is often associated with high costs, significant side effects, and poor adherence. Non-pharmacological interventions are increasingly explored as adjuncts to improve clinical outcomes, yet a comprehensive synthesis of this evidence is lacking. We conducted a scoping review and evidence gap mapping following the PRISMA-ScR guidelines. We systematically searched PubMed, Embase, and Cochrane Library from inception to May 2026 for studies evaluating non-pharmacological interventions in chronically transfused SCD patients with iron overload. Extracted data were synthesized into an evidence gap map to visualize the distribution of studies across intervention types and clinical outcomes. The search identified 14 eligible studies encompassing 642 participants. Interventions were categorized into dietary modifications (n = 5), nutritional supplementation (n = 4), physical activity (n = 3), and psychological/behavioral support (n = 2). The evidence gap map revealed a concentration of studies on short-term adherence and quality of life, with a notable paucity of long-term data on objective iron parameters (e.g., liver iron concentration) and organ-specific morbidity. The quality of evidence was generally low to moderate, limited by small sample sizes, lack of control groups, and heterogeneity in outcome measures. Non-pharmacological interventions show potential as adjuncts to iron chelation in chronically transfused SCD. However, significant evidence gaps remain, particularly regarding long-term objective outcomes. Future research should prioritize robust, longitudinal trials to establish standardized, evidence-based non-pharmacological protocols that can be integrated into comprehensive SCD care.