How I use allogeneic HSCT for adults with inborn errors of immunity

Abstract

Inborn errors of immunity (IEIs) are rare inherited disorders arising from monogenic germline mutations in genes that regulate the immune system. The majority of IEI are primary immunodeficiencies characterized by severe infection often associated with autoimmunity, autoinflammation, and/or malignancy. Allogeneic hematopoietic stem cell transplant (HSCT) has been the corrective treatment of choice for many IEIs presenting with severe disease in early childhood, and experience has made this a successful and comparatively safe treatment in affected children. Early HSCT outcomes in adults were poor, resulting in extremely limited use worldwide. This is changing because of a combination of improved IEI diagnosis to inform patient selection, better understanding of the natural history of specific IEI, and improvements in transplant practice. Recently published HSCT outcomes for adults with IEIs have been comparable with pediatric data, making HSCT an important option for correction of clinically severe IEIs in adulthood. Here we discuss our practice for patient selection, timing of HSCT, donor selection and conditioning, peri- and post-HSCT management, and our approach to long-term follow-up. We stress the importance of multidisciplinary involvement in the complex decision-making process that we believe is required for successful outcomes in this rapidly emerging area.