Challenges and limitations of mobilization and stem cell collection for gene therapy of sickle cell disease

ABSTRACT: Sickle cell disease (SCD) is a hemolytic anemia that afflicts millions of people worldwide and continues to carry high morbidity and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation was the only standard-of-care option for cure before the US Food and Drug Administration's approval of 2 cellular drugs. Transfusion medicine plays a pivotal role in supporting patients through mobilization and apheresis collection of peripheral blood stem cells and through transplant using standard or exchange transfusion strategies. Despite these advances, obtaining sufficient cells to generate a cellular gene therapy product and lack of standardized protocols that describe the optimal preparative regimen, mobilization, and collection of stem cells present a significant barrier to success. Our working group, convened as part of the National Heart, Lung, and Blood Institute-funded Cure Sickle Cell Initiative, sought to identify gaps in our understanding of these processes to improve advanced cell therapies for SCD.