Systemic Sclerosis: Hematopoietic Cell Transplantation
Hematopoietic (blood) cell transplantation (HCT) is a procedure that is now routinely used for treatment of hematological malignancies. The source of the blood stem cell can be from one’s own blood (autologous) or from a donor (allogeneic). Both types of transplantation can have a profound effect on the immune system. After intensive chemotherapy followed by autologous HCT, depletion of autoreactive immunologic memory has been observed. After allogeneic HCT, the autoreactive immune system is replaced by a donor-derived immune system without the predisposition to damage organs which were targets of the autoimmune disease.
Systemic sclerosis is a potentially life-threatening autoimmune disease, which is characterized by a vasculopathy and fibrosis of skin and internal organs. Skin fibrosis (or scleroderma) if extensive may severely restrict movement and functional abilities. Heart, lung, and kidney may fail as a result of the disease process. The gastrointestinal tract can also be extensively involved with marked dysfunction. Although immunosuppressive or immune modulating therapies are commonly used, none have been demonstrated to be a successful treatment for systemic sclerosis. Since no effective treatments had been identified for systemic sclerosis, studies were initiated in the late 1990’s to investigate the effectiveness of hematopoietic cell transplantation.
Several groups have now conducted pilot studies of high-dose immunosuppressive therapy (HDIT) followed by autologous HCT for patients with severe systemic sclerosis. Outcomes were thought to be promising. At 4 years after treatment, more than half of the patients were in remission, without progression of the disease and had not required any therapy since the transplant. A decrease in the extent of the scleroderma or skin re-modeling was observed. There was evidence for improvement in the vasculopathy as well. A randomized clinical trial with follow-up to 1 year showed that HDIT followed by autologous hematopoietic cell transplantation was much more effective than monthly doses of cyclophosphamide. Two other randomized clinical trials with longer follow-up are either still following patients or in the process of analyzing data and have not reported their results yet.
The Colorado Blood Cancer Institute in collaboration with the Scleroderma clinic at the University of Colorado is now conducting a new clinical trial of HDIT followed by autologous HCT (STAT). This clinical trial will investigate transplanting patients earlier in the course of their disease and will also investigate ways of reducing the risk of disease relapse after transplant. We will also be opening a clinical trial of allogeneic HCT for severe systemic sclerosis to assess if this may be more effective and responses more durable than HDIT followed by autologous HCT.