Effectiveness and risks of total body irradiation for conditioning in the treatment of autoimmune disease with autologous bone marrow transplantation

The results of experiments with the induced autoimmune diseases adjuvant ar thritis and allergic encephalomyelitis in rats, which led to the discovery of the curative effect of autologous bone marrow transplantation following high-dose myeloablative treatment, are reviewed. The rationale is eradicati on of the autoreactive lymphocytes and memory cells, and the prevention of relapse due to transfer of lymphocytes with the autograft. Comparison of va rious conditioning regimens in the animal models indicates that a combinati on conditioning with low-dose total body irradiation (TBI) and high-dose cy clophosphamide is optimal. These findings were the basis for the conditioni ng currently employed in the treatment of polyarticular juvenile chronic ar thritis (JCA) by the teams in Utrecht and Leiden, which consists of cycloph osphamide 50 mg/kg for 4 days, 4 Gy TBI and anti-thymocyte globulin (ATG). The use of TBI for the treatment of non-malignant disease is regarded as un desirable by many physicians in view of the risks, in particular, of growth inhibition in children and the induction of tumours. Experimental and clin ical data show that a dose of 4 Gy does not cause significant inhibition of skeletal growth in infants. The risk of excess cancer due to TBI has been well established in quantitative terms and is compared with the expected ri sk of high-dose cyclophosphamide and the risk associated with the highly im munosuppressive regimens currently used for the treatment of JCA.