Gene therapy for primary immunodeficiencies.

The concept of gene therapy emerged as a way of correcting monogenic inherited diseases by introducing a normal copy of the mutated gene into at least some of the patients' cells. Although this concept has turned out to be quite complicated to implement, it is in the field of primary immunodeficiencies (PIDs) that proof of feasibility has been undoubtedly achieved. There is now a strong rationale in support of gene therapy for at least some PIDs, as discussed in this article.

Hematopoietic stem cell transplantation for severe combined immunodeficiency diseases.

Hematopoietic stem cell transplantation (HSCT) is the only curative option for most children with severe combined immunodeficiency disease (SCID). Survival for SCID following HSCT has significantly improved over the past several decades, and ranges from 70% to 95% depending on the clinical condition of the child at the time of transplant, the availability of an HLA-matched sibling donor, and the SCID genotype/phenotype. In this article we will review the types of SCID and discuss the critical HSCT issues that confront us today, including the optimal source of donor cells when an HLA-matched sibling is not available, as well as the pros and cons of using conditioning therapy pretransplant. As SCID children have been followed for several decades, it is becoming apparent that long-term outcome and durable T and B cell immune reconstitution are quite variable depending on the initial treatment and source of donor cells. Finally, the development of methods to improve the early diagnosis of SCID along with designing prospective trials to evaluate the best approaches to curing these diseases with minimal toxicity are critical to improving outcomes for children with SCID.