Advances in the diagnosis and treatment of sickle cell disease

Sickle cell disease (SCD), which affects approximately 100,000 individuals in the USA and more than 3 million worldwide, is caused by mutations in the beta b globin gene that result in sickle hemoglobin production. Sickle hemoglobin polymerization leads to red blood cell sickling, chronic hemolysis and vaso-occlusion. Acute and chronic pain as well as end-organ damage occur throughout the lifespan of individuals living with SCD resulting in significant disease morbidity and a median life expectancy of 43 years in the USA. In this review, we discuss advances in the diagnosis and management of four major complications: acute and chronic pain, cardiopulmonary disease, central nervous system disease and kidney disease. We also discuss advances in disease-modifying and curative therapeutic options for SCD. The recent availability of l-glutamine, crizanlizumab and voxelotor provides an alternative or supplement to hydroxyurea, which remains the mainstay for disease-modifying therapy. Five-year event-free and overall survival rates remain high for individuals with SCD undergoing allogeneic hematopoietic stem cell transplant using matched sibling donors. However, newer approaches to graft-versus-host (GVHD) prophylaxis and the incorporation of post-transplant cyclophosphamide have improved engraftment rates, reduced GVHD and have allowed for alternative donors for individuals without an HLA-matched sibling. Despite progress in the field, additional longitudinal studies, clinical trials as well as dissemination and implementation studies are needed to optimize outcomes in SCD.

Automated summary

Sickle cell disease is a genetic disorder characterized by red blood cell deformation and end-organ damage. This review discusses advances in the diagnosis and management of major complications, as well as the latest developments in disease-modifying and curative therapies.