High dose cyclophosphamide followed by autologous stem cell transplantation for the treatment of intractable rheumatoid arthritis

Journal/Book: Z Rheumatol 1999; 58: 374-375. 1999;

Abstract: Prof. Dr. F. C. Breedveld; Department of Rheumatology C4R Leiden University Medical Center Leiden Rheumatoid arthritis (RA) is a chronic disabling disease primarily affecting the joints. Evidence points to a pivotal role of the immune system in the perpetuation of chronic synovitis. The interaction of CD4-positive autoreactive Th1 lymphocytes macrophages and synoviocytes is thought to underly chronic synovitis (1 2). As it was realised that RA is a disease in which autoreactive lymphocytes play an important role it was suggested that resetting the immune system might halt the disease process. The rationale for such a treatment comes from different observations. Preclinical studies in rat models with an adjuvant-induced polyarthritis have demonstrated effective control of the disease process by allogenic syngenic and also autologous bone marrow transplantation (BMT) after a myeloablative preparative regimen (3 4). Secondly several reports on patients treated with allogenic or autologous BMT for an hematological malignancy or severe aplastic anemia and coincidental autoimmune disease support the favourable effect of BMT on autoimmune diseases (5-9). Transplantation of hematopoietic stem cells after ablation of the recipient's immune system and subsequent deletion of autoreactive lymphocytes could therefore be a useful strategy to achieve remission in RA. However until recently mortality and morbidity of blood or marrow stem cell transplantation appeared too high to justify the risk of such a procedure in patients with autoimmune disease alone. The use of allogenic transplantation with its associated transplant-related mortality of 15-30% remains limited to selected cases. However autologous stem cell transplantation for patients with malignancies is associated with a transplant-related mortality of less than 5% (10-13). ... le

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