Progress in the field of hematopoietic stem cell-based therapies for inborn errors of immunity

Hematopoietic stem cell-based therapies, including allogeneic hematopoietic cell transplantation (HCT) and autologous gene therapy (GT), have been used as curative therapy for many inborn errors of immunity (IEI). As the number of genetically defined IEI and the use of HCT and GT increase, valuable data on outcomes and approaches for specific disorders are available. We review recent progress in HCT and GT for IEI in this article.

Novel approaches to prevention of allogeneic complications and experience in adolescents and young adults have expanded the use of HCT. Universal newborn screening for severe combined immunodeficiency (SCID) has led to improved outcome after HCT. Analysis of outcomes of HCT and GT for SCID, Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD) reveal risk factors for survival, the impact of specific conditioning regimens, and vector- or disease-specific impacts on efficacy and safety. Preclinical studies of GT and gene editing show potential for translation to the clinic.

Emerging data on outcome after HCT for specific IEI support early evaluation and treatment, before development of co-morbidities. Data in large cooperative retrospective databases continues to yield valuable insights clinicians can use in patient selection and choice of therapy.