Immune ablation with stem-cell rescue: a possible cure for systemic lupus erythematosus?

The impressive prolongation of survival has been the most important progress made in clinical systemic lupus erythematosus (SLE). Quality of life has also greatly improved, including pregnancy. However, persisting disease and therapy-related morbidity outcomes justify new approaches, different from the usual long-term palliative immunosuppression. Haematopoietic stem cells (HSCs) from healthy histocompatible mice are capable of curing murine SLE after eradication of the original HSCs with total body irradiation. Syngeneic and even autologous HSCs are also capable of curing induced experimental autoimmune diseases such as adjuvant arthritis and experimental allergic encephalomyelitis. In man allogeneic bone-marrow transplantation (BMT) is becoming progressively safer, but cannot yet be offered to SLE patients. However, syngeneic transplants from twins non-concordant for the disease would be justified. Conditioning with high-dose cyclophosphamide followed by autologous HSC rescue, from the marrow and/or from the peripheral blood, may already be regarded as a powerful immunosuppressive procedure for selected cases of SLE and other severe autoimmune diseases. Autologous transplant procedures are not saddled with the immunologic problems of allo-BMT. Although eradication of SLE may not be achieved by auto-BMT, minimal residual immunologic disease can be suppressed or controlled, and long-term self-maintained remissions may be expected.