Hematopoietic stem cell transplantation in systemic autoinflammatory diseases - the first one hundred transplanted patients

ABSTRACT

Introduction

Primary immune regulatory disorders encompass a range of clinical conditions caused by different defects of immune regulatory mechanisms, including systemic autoinflammatory diseases (AIDs). Allogeneic hematopoietic stem cell transplantation may be a therapeutic option for AIDs, particularly if response to conventional treatments is lacking.

Areas covered

HSCT has been reported as a possible therapeutic option in several AID subgroups, namely, inflammasomopathies, immuno-proteinopathies,actinopathies, relopathies, interferonopathies, and Adenosine Deaminase 2 deficiency. Here, an extensive review of the literature summarizes the available data on HSCT outcome in AIDs.

Expert opinion

HSCT in AIDs is mainly indicated in case of ineffectiveness of conventional therapies and/or co-existence of immunodeficiency in conditions characterized by a primary involvement of the hematopoietic compartment. An effective control of the inflammatory process before HSCT reduces the risk of alloreactivity. HLA identical family donor represents the first choice, but in most cases it is essential to exclude a possible carrier status. If a suitable HLA identical family donor is not available, a haploidentical donor with platform with T-depletion could offer some benefit lowering the risk of GvHD. Treosulfan-based conditioning regimens could be recommended to reduce toxicity and prevent rejection. Target chimerism may differ based on the primary disease’s pathogenic mechanism.

KEYWORDS:

• Autoinflammatory disease
• chimerism
• haploidentical transplant
• hematopoietic stem cell transplantation
• immunosuppression
• treosulfan

Article highlights

• HSCT in AIDs may represent a valid therapeutic option when conventional immunosuppressive treatment is unable to achieve a satisfactory control of the disease, especially in the presence of a concomitant defect of the immune response.

• HSCT should be considered in the presence of a prevalent involvement of the hematopoietic compartment.

• In most AID subgroups, the experience on HSCT is still largely anecdotal.

• Further studies are required to evaluate appropriate conditioning regimen, donor, and the level of sufficient lineage donor chimerism to cure the disease.

Acknowledgments

IRCCS G Gaslini is a member of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases — Project ID No 739543.

Declaration of interest

M Gattorno received speakers’ fees, consultancies and unrestricted grants from Novartis and Sobi.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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.