Pros and cons of stem cell transplantation for autoimmune disease

The data and discussion at this symposium have provided a most useful analysis of the autoimmune diseases and their potential for therapy by stem cell transplantation. These diseases are characterized by threat to life and particularly by chronic, painful and debilitating courses that warrant aggressive therapy. Selection of patients will be difficult because of the variable disease course and the necessity to choose patients who still have reversible disease. The safety of both autologous and allogeneic stem cell grafting has progressed to the point where, in many cases, the risks of the disease far outweigh those of transplantation. In my opinion the data presented at this symposium show that we should proceed cautiously with both autologous and allogeneic stem cell grafts. Purified stem cells, which have the advantage of being free of lymphocytes, should be used for the first series of autologous studies. These studies are attractive because of the low risk of transplant related complications but are less likely to be curative. Allogeneic grafts from perfectly matched donors have the advantage of providing a completely new immunological environment. For this reason, I believe that curative results are most probable after allogeneic stem cell engraftment. Emphasis should be on the identification of patients with HLA matched siblings. Initially, these studies will be carried out in patients with advanced disease, as was the case in the early days of transplantation for leukemia. In considering more aggressive treatment for autoimmune diseases it appears there are 3 possible approaches. First, and most conservative, is to store peripheral blood stem cells for possible future marrow rescue and then to give higher doses of immunosuppressive agents, especially in combination, to see whether there is an improvement over conventional doses. Second, for those who prefer a conservative approach to stem cell transplantation, is to give myeloablative and lymphoablative chemotherapy followed by purified (lymphocyte-free) hematopoietic stem cells. Third, and most likely to be curative, is myeloablative and lymphoablative therapy followed by stem cells from an HLA matched family member with subsequent short methotrexate and cyclosporine treatment to control GVHD. As we have heard, there are differences of opinion about whether the preparative regimen should include irradiation. It should be pointed out that total body irradiation is the most effective way to destroy lymphoid cells throughout the body. Careful monitoring of accumulating clinical results will pilot future investigation.