How I Treat Sickle Cell Disease with Gene Therapy

In 2023, two different gene therapies were approved for individuals with severe sickle cell disease (SCD). The small number of patients treated on the pivotal clinical trials that led to these approvals have experienced dramatic short-term reductions in the occurrence of painful vaso-occlusive crises, but the long-term safety and efficacy of these genetic therapies are yet to be ascertained. Several challenges and treatment-related concerns have emerged in regard to administering these therapies in clinical practice. In this article, I discuss the selection and preparation of individuals with SCD who wish to receive autologous gene therapies. I also review salient features of the care needed to support them through the long and arduous treatment process. I specifically focus on post-infusion care, as it relates to immune monitoring and infection prevention. Compared with allogeneic hematopoietic cell transplantation, delivering autologous gene therapy to an individual with SCD has distinct nuances that require awareness and special interventions. Using clinical vignettes derived from real-life patients, I provide perspectives on the complex decision-making process for gene therapy for SCD, based on currently available data, and I make recommendations for evaluating and supporting these patients.