ABSTRACT
Hematopoietic stem cell transplantation holds great promise for treating autoimmunity. The source of hematopoietic stem cells can be from a normal donor (allogeneic) or from the patient (autologous). Due to the high morbidity and mortality of traditional allogeneic stem cell transplantation, most centers are pursuing the use of autologous stem cell transplantation for the treatment of autoimmune diseases. There are three major components to autologous stem cell transplantation: (1) stem cell collection (mobilization); (2) conditioning with high-doses of chemotherapy; and (3) stem cell infusion. However, for treating autoimmunity with autologous stem cell transplantation, the therapeutic efficacy (high-dose immunosuppression) is derived from the conditioning regimen; hematopoietic stem cells are used as a rescue procedure. Most centers utilize mobilized peripheral blood progenitors as a source of stem cells. Cyclophosphamide (2 to 4 g/m2) combined with granulocyte-colony stimulating factor (G-CSF) is the most frequently employed regimen to mobilize hematopoietic stem cells, but other regimens including G-CSF and corticosteroids have been used successfully. A concern with autologous stem cell transplantation for autoimmunity is that the mobilized product contains several logs of effector cells (lymphocytes) which may, theoretically, re-establish the disease. Therefore, most groups purge the autograft of contaminating lymphocytes. Due to its potent immunosuppressive activity, high-dose cyclophosphamide forms the basis of most conditioning regimens used for autoimmunity. High-dose cyclophosphamide is non- myeloablative; thus, high-dose cyclophosphamide without stem cell rescue has been employed to treat autoimmune disease.
