Hematopoietic cell transplantation in primary immunodeficiency - conventional and emerging indications

Abstract

Hematopoietic stem cell transplantation (HSCT) is an established curative treatment for many primary immunodeficiencies. Advances in donor selection, graft manipulation, conditioning and treatment of complications, mean that survival for many conditions is now around 90%. Next generation sequencing is identifying new immunodeficiencies, many of which are treatable with HSCT. Challenges remain however with short and long-term sequalae. This article reviews latest developments in HSCT for conventional primary immunodeficiencies and presents data on outcome for emerging diseases, Areas covered: This article reviews recently published literature detailing advances, particularly in conditioning regimens and new methods of T-lymphocyte depletion, as well as new information regarding approach and out come of transplanting patients with conventional primary immunodeficiencies. The article reviews data regarding transplant outcomes for newly described primary immunodeficiencies, particularly those associated with gain-of-function mutations. Expert commentary: New methods of graft manipulation have had significant impact on HSCT outcomes, with the range of PIDs treated using T-lymphocyte depletion significantly expanded. Outcomes for newly described diseases with variable phenotypes and clinical features, transplanted when the diagnosis was unknown are beginning to be described, and will improve as patients are identified earlier, and targeted therapies such as JAK inhibitors are used as a bridge to transplantation.

Keywords: DOCK8 deficiency; Hematopoietic stem cell transplantation; IPEX syndrome; Lipopolysaccharide-responsive and beige-like anchor protein deficiency; TCRαβ depletion; Wiskott-Aldrich syndrome; activated PI3K-δ syndrome; chronic granulomatous disease; cytotoxic T lymphocyte antigen-4 deficiency; severe combined immunodeficiency; signal transducer and activator of transcription 1 gain of function; virus-specific cytotoxic T-lymphocytes.