Immune ablation followed by allogeneic or autologous bone marrow transplantation: A new treatment for severe autoimmune diseases?

Among the over 40 disorders recognized at present as having an autoimmune pathogenesis [ 1 , 21 there are a significant number of severe diseases which can only be partially controlled by the customary long-term immunodepressive therapy, which has not abolished the “significant sum of human misery” [3] that is inevitably associated with the diseases and their treatment, Taking systemic lupus erythematosus (SLE) as a prototype of generalized autoimmune diseases [4], even with some reservations [l], there exists an entire spectrum of negative consequences of long-term immunodepressive and corticosteroid therapy, including opportunistic infections, coronaropathies, avascular necrosis of bones and neuropsychological cognitive dysfunctions. This has been regarded as the “price of therapy” [5], and a “damage index” has been proposed. Much progress has been made recently in the understanding of etiopathogenesis of autoimmune diseases, thanks mainly to the powerful techniques of molecular biology and genetic engineering [6-81. But the concept of a multifactorial pathogenesis is still prevalent [ 11, and it has been predicted that no single external factor will account for autoimmune disease [9]. An innovative immunological approach is being actively pursued, based on T cell-directed immunointerventions [ 10-IS]. Although this type