Intense immunosuppression plus stem-cell transplantation (SCT) has emerged as a new treatment modality for patients with refractory, severe rheumatic autoimmune disease. Its rationale is based on eliminating autoaggressive lymphocytes by lympho- or myeloablative conditioning followed by stem-cell rescue. Preclinical studies in animal models of autoimmune disease and observations in patients with rheumatoid arthritis (RA) who were cured after allogeneic bone marrow transplantation for concomitant hematologic malignancy have provided support for the concept.

The authors reviewed the results of recent phase I/II studies and data from the EBMT/EULAR Registry on more than 400 patients with autoimmune diseases including RA, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and juvenile idiopathic arthritis (JIA).

Toxicity resulting from stem-cell grafting depended on underlying disease and the intensity of the conditioning regimen. Treatment-related mortality was low in RA (1.4%) but relatively high (>10%) in patients with JIA, SLE, and SSc, possibly related to visceral involvement in these patients. With the application of uniform and strict criteria, safety has improved. Long-term remissions up to 4 years have been observed in SSc and JIA, while relatively more relapses have occurred in patients with SLE and RA. Sensitivity to anti-rheumatic drugs was restored in RA and SLE patients, however, resulting in improved disease control.

Intense immunosuppression and SCT may be an effective therapy for selected patients with severe rheumatic autoimmune disease. Its merits need to be proven via multicenter phase III studies by comparing efficacy and safety with conventional therapy.