High-Dose Immunosupression and Stem Cell Transplantation in Severe Autoimmune Diseases

High-dose chemotherapy followed by hematopoietic stem cell (SC) transplantation has been recently proposed as a new strategy for the treatment of severe autoimmune diseases. The rationale for using stem cell transplantation to treat autoimmune disease is based on the principle of complete ablation of an aberrant immune system followed by reconstitution of a new immune system deriving from graft. Three different approaches are being currently used: 1) allogeneic SC transplantation, 2) autologous SC rescue following "immunoablation", and 3) intensive immunosuppression alone. By October 2000, a total of 310 patients who received SC transplantation for autoimmune diseases were registered in the European Group for Blood and Marrow Transplantation/European League Against Rheumatism. Five patients with primary severe autoimmune diseases (4 female and 1 male) were enrolled in our Institute from 1998 to 2000. Transplantations were made for systemic lupus erythematosus (SLE, n = 4) and idiopathic thrombocytopenic purpura (ITP, n = 1). Three SLE patients had lupus nephritis, lung vasculitis with pulmonary hypertension, secondary antiphospholipide syndrome, 1 SLE patient had central nervous system involvement with paraplegia, patient with ITP had a relapse after splenectomy and had unresponsive severe thrombocytopenia. Follow up is now 24 months for 1 SLE patient (she is in complete remission), 12 months for the 2nd SLE patient (partial response), ITP patient is well at present, platelets >100 x 10(9), dose of prednisolone is 10 mg/day. 2 SLE patients died on day +11 and +19 due to transplant-associated complications (sepsis). The study is still ongoing and longer follow-up is necessary to assess long-term efficacy of this treatment approach.