Stem Cell Therapy of IBD

Extract

Autoimmune diseases are thought to develop when committed autoaggressive clones develop through environmental triggers in genetically susceptible individuals. By eradicating or regulating committed clones, immunoablation followed by hematopoietic stem cell transplantation (HSCT) offers the prospect of restoring patients with established disease to being no more than susceptible to disease. Around 1000 patients suffering from severe autoimmune disease have received HSCT in the past 10 years. The main autoimmune diseases treated have been multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and juvenile idiopathic arthritis. The European experience has been recently published,¹ showing durable remission in around one third of cases with a 7% transplant related mortality, variable between the different autoimmune diseases. Prospective randomized trials are running or about to start in multiple sclerosis, systemic sclerosis, systemic lupus erythematosus in Europe and the United States.

Most HSCTs were autologous, and most received a nonmyeloablative regimen. Toxicity correlated with age, intensity of the conditioning, and general state of the patient at transplant. Twenty-six allogeneic HSCTs have been registered, mostly for hematological autoimmune diseases. No clear advantage of allogeneic over autologous HSCT has emerged regarding relapse rates. In the literature, case reports have shown both long-term remission and full relapse with autologous, syngeneic, and allogeneic HSCT for autoimmune disease. A recent autologous HSCT study from the National Institutes of Health confirmed that clinical remission was maintained in patients with multiple sclerosis after full immunological reconstitution had occurred, suggesting a "resetting" of autoaggression rather than an eradication.² The concept of graft versus autoimmunity remains hypothetical whereas the increased toxicity of allogeneic HSCT due to GvHD is an immutable reality.