Scleroderma, also known as systemic sclerosis (SSc), is a disabling disease. The body attacks its own tissues, causing an overproduction of collagen. Collagen is a fiber-like protein which holds all of the structures in the body together. Patients often suffer fatigue, joint swelling and/or pain, and a loss of appetite and weight. Scleroderma can be difficult to diagnose because it overlaps with or resembles other conditions. Severe forms of the disease typically cause significant thickening and stiffening of the skin. Internal organs are affected, resulting in damage to the heart, lungs, kidneys, and gastrointestinal tract.

Severe forms of the disease, particularly rapidly progressive diffuse SSc with involvement of internal organs, are associated with a high death rate. Studies have shown poor prognosis of patients with internal organ involvement and suggest that clinicians can identify a subpopulation of SSc subjects of high risk for death who may benefit from a more aggressive therapeutic approach. The progression of SSc and the development of new organ disease despite conventional treatment is another signal for clinicians to be more aggressive in therapy.

Many treatments have been tried for severe SSc, but none has been proven effective in preventing disease progression or reversing fibrosis in randomized, controlled trials. Although the exact cause of scleroderma is unknown, the immune system is thought to play a major role in the development of the disease, and there is some evidence to suggest that immune-based therapies are beneficial. Oral cyclophosphamide taken daily had been compared to placebo in a randomized clinical trial of patients with lung disease from scleroderma. The cyclophosphamide was shown to be beneficial though the effect was small. Cyclophosphamide may improve the skin disease as well. The effectiveness of intravenous cyclophosphamide used at the doses in this study has not been evaluated in a formal controlled clinical trial.

In response to the absence of an effective treatment for SSc, autologous hematopoietic stem cell transplantation (HSCT) has been proposed as a potential therapy. Hematopoietic stem cells are immature blood cells that can develop into any of the different blood and immune cells your body uses. Researchers believe that resetting the immune system may stop the progression of the disease. The main purpose of this study is to compare the two ways of treating SSc: 1) high-dose immunosuppressive therapy (HDIT) followed by HSCT and 2) high-dose pulse IV cyclophosphamide (CTX).