Haematopoietic stem cell transplantation in autoimmune diseases: From basic science to clinical practice.
Based on animal studies and serendipitous clinical cases, haematopoietic stem cell transplantation (HSCT) has been used since 1995 as a specific treatment for patients with severe treatment-resistant autoimmune disease (ADs). Despite other clinical developments for autoimmune diseases, including biological therapies, there has been an ongoing requirement for HSCT in some diseases and several thousand procedures have been registered in databases for a wide variety of diseases, predominantly for treatment with autologous HSCT. Currently, the main indications are multiple sclerosis, systemic sclerosis and Crohn's disease, which are supported by large series and randomised controlled trials (RCTs), whereas retrospective registry analyses support benefit in a range of rarer indications. Research into mechanisms of action has provided insight into how tolerance may be achieved with an intensive one-off treatment. In addition to the profound anti-inflammatory and immunosuppressive effects provided by the cytotoxic regimen, long-term responses in some diseases may be explained by 'resetting' the immune system through thymic reprocessing and generation of increased T-regulatory cell activity. This review aims to summarise the gradual evolution of HSCT in severe autoimmune diseases over the last 20 years, focussing on the recent publication of clinical and scientific studies, as well as evidence-based guidelines and recommendations.
Departments of Haematology and Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK. Electronic address: philippakelsey24@hotmail.com.
P J
PJ
Kelsey
Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
M-C
MC
Oliveira
EBMT Study Office, Paris, France.
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M
Badoglio
Departments of Haematology and Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK.
B
B
Sharrack
St. Louis hospital, Internal Medicine and Vascular Diseases Unit, Paris, France; INSERM 1160 Unit, Paris 7 Diderot University, Sorbonne Paris Cite 1, Paris, France.
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D
Farge
Departments of Haematology and Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK.
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JA
Snowden
D064591:Allografts; D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D003424:Crohn Disease / Q000628:therapy; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000592:standards / Q000639:trends; D006801:Humans; D051379:Mice; D015337:Multicenter Studies as Topic; D009103:Multiple Sclerosis / Q000628:therapy; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000628:therapy; D057170:Translational Research, Biomedical / Q000639:trends; D014182:Transplantation, Autologous
Autoimmune; Bone marrow; Stem cell