Over the last 40 years, survival following T-lymphocyte depletion in hematopoietic stem cell transplantation (HSCT) for primary immunodeficiency has remained unsatisfactory when compared to results when utilizing matched siblings or matched unrelated donors. Three novel methods, however, are dramatically changing the approach to HSCT for people who do not have a matched donor, particularly those with initial immunodeficiencies that are not severe combined immunodeficiency. Three key T-lymphocyte depletion methods are changing donor choice for patients with primary immunodeficiencies and have increased transplant survival for primary immunodeficiencies to over 90%, comparable to matched siblings and matched unrelated donor transplants. CD3+ TCR+ CD19+ depletion, CD45RA depletion, and use of posttransplant cyclophosphamide all result in a comparable overall survival rate of 90%, while viral reactivation remains a risk. Further modifying CD3+ TCR+ CD19+ depletion by reintroducing inducible caspase-9 suicide gene-modified CD3+ TCR+ T-lymphocytes may enhance outcomes for patients with systemic viral infection.
Over the last five years, the outcomes of HSCT using new T-lymphocyte depletion methods have improved to the point where they are equivalent to the outcomes of matched sibling donors and may be preferred over an unrelated donor in the absence of a fully matched sibling donor to reduce the risk of graft versus host disease.