Clinical considerations in the hematopoietic stem cell transplant management of primary immunodeficiencies

Primary immunodeficiencies (PID) are genetic immune disorders causing increased predisposition to infections and autoimmunity. The only curative procedure is hematopoietic stem cell transplantation (HSCT), results from which have improved dramatically since 2000. Complications remain a serious issue, especially in HLA non-identical transplantation. In PID patients, persistent infection and autoimmunity with end-organ damage cause particular problems with approach to transplantation. This article examines these, emphasising approach to management and consequences. Areas covered: It is challenging to know which patients should be offered HSCT. As new diseases are discovered, data are required to determine natural history, and HSCT outcomes. Treatment of adults can be challenging, although HSCT outcomes are encouraging. New methods of T-lymphocyte depletion show results comparable to those of matched sibling donor transplants. New cellular therapies to treat viral infections show promising results, and immunomodulatory methods are successful in treating acute graft-versus-host disease. Expert commentary: New T-lymphocyte depletion methods are a paradigm shift in approach to HSCT for PID. In combination with new cellular approaches to treating viral infection, immunomodulatory approaches to acute graft-versus-host disease and better understanding of endothelial activation syndromes, survival approaches 90%. Widespread introduction of newborn screening for severe combined immunodeficiencies will improve survival further.