Hematopoietic cell transplantation in primary immunodeficiency – conventional and emerging indications

ABSTRACT

Introduction: 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:

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

Declaration of interest

MA Slatter has received honoraria from Medac for speaking. AR Gennery has received honoraria from Mallinckrodt and Jazz Pharmaceuticals for speaking. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was not funded.