Stem cell transplantation in sickle cell disease: therapeutic potential and challenges faced

Abstract

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide, and is a life-limiting disease with limited therapeutic options to reduce disease severity. Despite being a monogenic disorder, the clinical phenotypes of SCD are variable, with few reliable predictors of disease severity easily identifying patients where the benefits of curative therapy outweigh the risks. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option, though significant advances in gene therapy raise the promise for additional curative methods. Areas covered: Allogeneic transplantation in SCD has evolved and improved over the last two decades, now offering a standard of care curative option using a human leukocyte antigen (HLA)-matched sibling donor. Many of the seminal transplantation studies are reviewed here, demonstrating how initial failures and successes have influenced and led to current HSCT strategies. Such strategies aim to overcome setbacks and limitations, and focus on conditioning regimens, immune suppression methods, the use alternative donor sources, and gene therapy approaches. Expert commentary: SCD is a curable disease. Each dedicated effort to refine transplantation methods, expand the donor pool, and bring gene therapy models to fruition will make enormous impacts reducing disease burden and improving outcomes and quality of life for patients with SCD.

Keywords: Allogeneic transplantation; autologous transplantation; gene therapy; hematopoietic stem cell transplantation; sickle cell disease.