Abstract
Intractable forms of autoimmune diseases follow a rapid course, with a significantly shortened life. expectancy sometimes comparable to that of malignant diseases. Immunoablative therapy; including high dose cytotoxic agents and hematopoietic autologous stem-cell rescue, was recently introduced as an aggressive approach to treat autoimmune diseases that-have a rapid course and are resistant to conventional therapy.
The most frequent indication for this type of treatment is multiple sclerosis, seconded by systemic sclerosis. The results of immunoablative treatment with documented responses in both diseases are encouraging.
The data are mature enough to begin comparative randomized studies of immunoablative versus conventional treatment to validate the benefit, of the aggressive approach. A randomized trial involving SSc was recently launched (ASTIS) and a trial involving MS is in preparation: Considerably less experience with; immunoablative treatment has, been gained in systemic lupus erythematosus, rheumatoid arthritis, and other disorders with an autoimmune pathophysiology.
Autologous hematopoietic stem cell transplantation in humans offers more long-lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic transplantation may replace the whole immune, system.
However, this attractive approach is still associated with considerable morbidity and mortality and is not yet justified for treatment of automimmune diseases. Non-myeloablative allogeneic transplantation and sub-myeloblative high dose cyclophosphamide without stem cell support are alternative approaches that could be explored in pilot studies