Therapeutic decision making in BMT/SCT for autoimmune disorders

Introduction page 227 Multiple sclerosis 228 Rheumatoid arthritis 229 Systemic lupus erythematosus 229 Future perspectives 230 Further reading 230 Introduction Severe autoimmune disorders often have a chronic relapsing course characterized by flare-ups, remissions, further progression, and finally incapacitation. Autoimmune disorders may target many different organ systems. Multiple sclerosis is characterized by inflammation and an autoimmune attack on myelin fibers, resulting in demyelination and later axonal loss. Rheumatoid arthritis is characterized by an autoimmune attack against the synovial membrane, resulting in chronic inflammation and joint destruction. In severe cases, autoimmune disorders may cause death from multiorgan involvement. A common principle for the treatment of most autoimmune disorders is immunosuppression. The evidence for the value of high-dose chemotherapy with stem cell support comes from three lines of evidence: (a) it was speculated that higher dose immunosuppression or immunoablation could eliminate the pathogenic autoreactive cells more thoroughly; (b) in a number of case reports patients who underwent a bone marrow or stem cell transplant for a hematologic malignancy and had a coincidental autoimmune disorder came into remission of both diseases (Drachman et al., 2005); and (c) it could be demonstrated in animal experiments that the transfer of syngeneic stem cells following immunoablation may cure several autoimmune disorders (Sykes et al., 2005). Overall, more than 700 patients with a variety of autoimmune disorders have undergone an autologous stem cell transplant (Tyndall et al., 2005). A recent review was written by Rosa et al. (2007). In this chapter I will review the treatment results for multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, as well as discuss future developments.