Rare Disease Day 2018 is on 28 February, 10 years since it first took place in 2008. This year’s theme is research. For this occasion, we have asked our two EBMT working parties chairs - John Snowden, Chair of the Autoimmune Diseases Working Party and Arjan Lankester, Chair of the Inborn Errors Working Party - to explain why rare diseases have a high profile within the EBMT.
For over 40 years across Europe, the EBMT have been pooling our knowledge in rare disorders, and subsequently have been able to significantly enhance the field in relation to those rare diseases where BMT is of benefit. The Inborn Errors (IEWP) and Autoimmune Diseases Working Parties (ADWP) of EBMT are a good model for scientific collaboration for Blood and Marrow Transplantation (BMT) in rare diseases.
Within the IEWP several important developments have advanced the treatment of patients with rare inherited immune disorders. First, more effective and safer stem cell transplantation procedures have been developed which have resulted in increasingly successful outcomes. Secondly, better understanding of the molecular basis of particularly inherited inflammatory and immune dysregulations disorders has provided the rationale that some of these patients can be cured by allogeneic stem cell transplantation. Most of this progress has been achieved through multinational collaborations and studies in which IEWP has played a leading role. Increasing knowledge of the genetic basis of rare immune disorders and related diseases has resulted in the preclinical development and clinical translation of stem cell gene therapy as a promising alternative for allogeneic stem cell transplantation. In recent years several clinical trials have been performed with a focus on severe combined immune deficiency, and very encouraging results have been obtained. Several of these gene therapy studies are conducted in multicenter consortia supported by the European Union. In these innovative consortia (eg. SCIDNET and RECOMB) patient organisations are actively involved in the development of clinical trials. Early identification of patients with severe immune deficiency is likely to contribute to a more timely and thereby effective treatment of new borns. With that aim, new born screening for severe combined immune deficiency is currently being explored and implemented in several European countries.
A good example in the ADWP activity has been the progress made over the last 5 years in relation to systemic sclerosis, a rare autoimmune disease affecting skin and internal organs. Systemic sclerosis is a potentially life threatening condition, with a prognosis of 3-5 years in severely affected patients. Until recently there has been no treatment that can influence the disease course and management has been largely supportive care and symptom control. This has changed recently with now three randomised controlled trials supporting a survival benefit with autologous BMT. The EBMT ADWP has been central to this research, with not only the publication of the ASTIS trial, but also many studies analysing real world data in the EBMT registry. Further fine tuning is ongoing within the EBMT, but now BMT is being increasingly accepted as an effective treatment option in poor prognostic patients. Guidelines have been produced for patient selection and treatment by the ADWP. Other rare autoimmune diseases, mainly neurological and rheumatological, also feature in the EBMT registry and have been the subject of rare disease analyses and ongoing guidelines which can help to support patient selection, treatment schedules and funding of procedures.
Advances in rare diseases are not all therapeutic - access to appropriate diagnostic techniques, such as genome sequencing, have enabled diagnosis of patients with hitherto uncharacterised rare diseases. The EBMT working parties try to integrate all of these diagnostic and prognostic advances into their clinical studies and guidelines.
EBMT also has a long history of patient engagement - most visibly in the patient and donor day which is an integral part of the EBMT Annual Meeting. This brings patients, families, scientists and clinicians together in the same place enabling exchange of knowledge and views, and allowing patient experience to shape our future direction, but importantly, giving patients access.