Optimizing the “right” patient selection for treatment for sickle cell disease

Abstract Sickle cell disease (SCD), the most prevalent hemoglobinopathy globally, is a complex, systemic disorder with significant phenotypic variability and evolving clinical burden. As the therapeutic landscape expands—ranging from hydroxyurea and red blood cell transfusions to novel disease-modifying agents and curative approaches, such as hematopoietic stem cell transplantation and gene therapy—patient selection for each strategy becomes increasingly multifaceted. This article explores how clinical severity, genotype, age, organ involvement, access to care, and patient preferences interact in shaping therapeutic decisions. Two illustrative cases highlight how disease trajectory, individual choices, and real-world barriers influence eligibility and response to treatment. We propose a multidimensional framework for patient selection, incorporating both clinical indicators and patient-centered outcomes. While monotherapy with a single disease-modifying therapy remains the cornerstone of SCD treatment, all therapeutic decisions should be individualized. However, combination and curative approaches are more complex and require a comprehensive evaluation of efficacy, feasibility, and patient values. Emerging trends, including biomarker-driven stratification, inclusive clinical trials, and shared decision-making tools, coupled with the use of artificial intelligence, offer opportunities to better align therapy with the needs of diverse patients across settings. Ultimately, defining the “right” patient demands dynamic, context-sensitive evaluation, ensuring that therapeutic advances translate into equitable and valuable care for individuals with SCD globally.