Vorträge - Dgrh-Kongress

Thema: Systemsklerose, Sjögren, Myositiden
06.03
Autologous haematopoietic stem cell transplantation in systemic sclerosis.
van Laar J.M. 1
(1) Institute of Cellular Medicine, Musculoskeletal Research Group - 4th Floor Cookson Building, Newcastle
upon Tyne
Systemic sclerosis (SSc) is a potentially life-threatening chronic autoimmune disease characterized by skin
thickening, vasculopathy, and visceral involvement. Diffuse cutaneous SSc generally runs a more aggressive
disease course, requiring intensive immunosuppressive therapy. In pilot studies and registry analyses
haematopoietic stem cell transplantation (HSCT) was shown to result in steady and sustained improvement
of skin thickening and stabilization of organ involvement (heart, lung, kidney), but at the expense of mainly
cardiopulmonary toxicity culminating in treatment-related mortality in about 10% of transplanted SSc
patients. The development of HSCT as treatment for autoimmune disease has followed a learning curve and
it is now well appreciated that some of the toxicities of HSCT can be avoided by exclusion of high-risk
patients and specific precautions related to the management of transplanted patients.
Mechanistic studies have been shown that HSCT in autoimmune disease induces fundamental changes of
the immune system, resulting in lower serum concentrations of autoantibodies, correction of cytokine
imbalances, induction of regulatory T cells and breakdown of excessive collagen production. Interestingly,
significant clinical improvements have also been observed in patients with persistent titers of Scl-70
antibody, suggesting that changes in autoantibody are secondary to alterations in underlying disease
pathways.
Given the costs and risks of HSCT, especially in SSc and SLE patients, screening of potentially eligible
patients is critical. This should involve comprehensive cardiopulmonary screening, and may lead to exclusion
of patients who have no other treatment options. Ongoing multicentre clinical trials (ASTIS in Europe, SCOT
in USA) will determine whether the benefits of HSCT outweigh the risks when compared to standard
cyclophosphamide treatment, and whether baseline predictors for responsiveness can be identified. The first
outcome data from the ASTIS trial, conducted by the EBMT/EULAR Scleroderma Study Group, are expected
after Oct 2011, while accrual in the NIH-sponsored SCOT trial has just been completed. Until the results of
these trials become available and confirm the superiority of HSCT over standard chemotherapy, HSCT
should be considered an investigational treatment, eg as part of a so-called non-interventional trial, for
patients with poor-prognosis SSc.