Originally supported by animal models and serendipitous clinical reports, haematopoietic stem cell transplantation (HSCT) has been evolving since 1996 as a specific treatment for patients with severe autoimmune disease (ADs) refractory to conventional treatments. With this emerging clinical practice, the EBMT Autoimmune Disease Working Party (ADWP) was created in 1997 on the initiative of Professors Alois Gratwohl, Alan Tyndall and Alberto Marmont. A database and best practice guidelines were the first steps.
Chairs and Secretaries
Chairs and their respective Secretaries were successively:
From 1998-2004: Professor Alan Tyndall (Rheumatology, Basel, Switzerland), who worked with Professor A Fassas (Haematology, Thessaloniki, Greece) as Secretary.
From 2004-2010: Professor Riccardo Saccardi (Haematology, Firenze, Italy) chair with Professor Dominique Farge (Internal Medicine, St Louis Hospital, Paris France) as Secretary.
From 2010-2016: Professor Dominique Farge (Internal Medicine, St Louis Hospital, Paris France) working with Professor John Snowden (Haematology, Sheffield, UK) as Secretary.
Since April 2016: Professor John Snowden (Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK) with Dr Tobias Alexander (Rheumatology/Immunology, Charite Hospital, Berlin, Germany) as Secretary.
The ADWP business meetings are held twice per year: with the EBMT Annual Meeting programme and in conjunction with the Autumn educational symposium. Membership criteria have been agreed and the ADWP aims to ensure fair and effective representation of both haematologists and disease specialists from all countries involved in the field in the EBMT. The ADWP Chair attends the EBMT Board Meetings 4 times a year to discuss the advancement of ongoing studies and new study proposals, and review abstracts and manuscript submission.
The ADWP also plays a strategic role of interacting with other European autoimmune disease specialists and their respective scientific societies and groups, and regulatory stakeholders, both at the European levels and at the International levels such as:
- The European League against Rheumatism (EULAR) and its related working groups on: Scleroderma: European Group for Scleroderma Clinical Trials (EUSTAR); Lupus: the Eurolupus Group; Vasculitis: European Vasculitis Society (EUVAS)
- The European Crohn’s and Colitis Organisation (ECCO)
- The European Committee for Treatment and Research in Multiple Sclerosis, (ECTRIMS)
Current status of the disease/condition and reasons for treatment with HSCT/Cellular Therapy
Multidisciplinary guidelines were published by the ADWP from an early stage to advise on selection and management of patients (Tyndall & Gratwohl 1997). These have been updated (Snowden et al 2012) and guidelines for immune monitoring and biobanking have been published (Alexander et al 2015).
Autoimmune Diseases in the Registry
Over the last 20 years, over 2000 HSCT procedures have been reported to the ADWP database from around 200 centres in 40 countries. The main indication has been multiple sclerosis (MS), followed by rheumatological conditions, Crohn’s disease, haematological immune cytopenias, and, recently, type 1 diabetes. The predominant countries of activity have been Italy, Germany, the Netherlands, UK, Spain France and Sweden. There was a peak of activity in 1999 followed by a transient fall in activity coincident the widespread availability of biological therapies and a gradually increasing trend from 2006 to the present, with MS, SSc and Crohn’s disease as the current commonest indications based on the increasing evidence base.
Retrospective analyses using ADWP database have provided evidence for the feasibility and the toxicity of autologous HSCT procedures across a large number of ADs, including multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), vasculitis, juvenile chronic arthritis (JIA), neuromyelitis optica, chronic demyelinating inflammatory polyneuropathy and paediatric diseases. Several retrospective analyses have also been performed on the database as a whole. Retrospective analysis of limited numbers of allogeneic HSCT has also been performed.
Randomised controlled trials (RCTs) have also been conducted under the EBMT ADWP (ASTIS, ASTIMS and ASTIC).
The ASTIS trial, a prospective EBMT-EULAR multicenter, randomized phase III study to compare autologous hematopoietic stem cell transplantation with intravenous pulse therapy cyclophosphamide in severe systemic sclerosis, was launched in 2000 and published in 2014.
The ASTIMS was a multicenter randomized study to evaluate autologous HSCT versus mitoxantrone in severe multiple sclerosis, which was published in 2015.
The ASTIC trial, a multicentre, randomised study conducted by the ECCO and the EBMT in Crohn’s disease to evaluate hematopoietic stem cell mobilisation alone followed by best clinical practice versus by high dose immuno-ablation and autologous HSCT has completed and is submitted for publication.
A number of prospective non-interventional studies are in development or active.
Collaboration and interaction
There has always been active collaboration with other Working Parties (WP), notably the Transplant Complications WP, Paediatric Diseases WP, Lymphoma WP, Severe Aplastic Anaemia WP and Cellular Therapy and Immunobiology WP. There is regular interaction and successful collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR).
There has been active collaboration with many scientific colleagues – from translational work aimed at elucidating mechanisms of response to HSCT in various autoimmune diseases to health economic studies.
The ADWP also promote awareness, teaching and knowledge about HSCT and other blood derived Cell Therapies for Autoimmune Diseases. As other important advances have happened in rheumatology, neurology and gastroenterology in the last two decades there has always been a priority to take a balanced view of the role of HSCT against evolving treatment, and other specialties are routinely invited to our educational sessions.