Haematopoietic stem cell transplantation for the treatment of systemic sclerosis and other autoimmune disorders

Systemic sclerosis (SSc) with involvement of vital organs has up to 50% 5year mortality and no treatment is known which changes the natural history. Although components of vascular, immunological and fibrotic processes are involved, drugs such as cyclophosphamide (CY), an alkylating agent and a potent immunosuppressive, have been partially effective in uncontrolled studies. The dose of such agents is limited by the inevitable toxicity on the bone marrow, but this threshold may be superseded by first removing the patient’s own haematopoietic stem cells, followed by reconstitution of the marrow after high-dose myeloablative CY or other therapy. This autologous haematopoietic stem cell transplantation (HSCT) technique has been applied to 650 patients with severe autoimmune diseases worldwide, > 100 of whom had SSc. Of these, 75 are included in the Basle registry. Around 70% of patients responded with a significant (> 25%) improvement of the thickened skin and stabilisation of vital organ involvement. Approximately a third achieved a durable remission. The treatment-related mortality was 8.5%. Based on these encouraging Phase I/II study results, several multi-centre, international, prospective randomised Phase III trials are running or being planned. The preliminary data suggest that through such a jolt of heavy immunosuppression, the dysregulated autoaggressive immune system may be re-regulated. It is hypothesised that this results in fewer autoinflammatory and unwanted stimulatory signals to other systems such as vascular endothelium and fibroblasts, and these mechanisms are currently under study.