Systemic Sclerosis (Scleroderma) varies greatly in clinical manifestations, mode of presentation, and course. The natural history of this chronic autoimmune disease ranges from benign to fatal. Patients are classified into limited and diffuse scleroderma defined by the degree of skin involvement. Patients with limited disease (e.g. the C.R.E.S.T. syndrome) generally have mild disease and normal survival. However, patients with diffuse cutaneous scleroderma often have severe multi-system disease that is not only devastating emotionally and physically but is associated with a 60-70% five year survival and a 40-50% 10 year survival. No therapies have proven effective in the treatment of scleroderma. Strategy to treat scleroderma have included attempts to prevent fibrosis with drugs that interfere with collagen metabolism, attempts to modify the disease process by immunosuppression and attempts to alter the disease by vasoactive drugs. High dose of corticosteroids and other immunosuppressive drugs (e.g. chlorambucil, 5-fluorouracil, methotrexate, cyclophosphamide, cyclosporine) used at conventional doses have not proven curative, but have shown some benefit for inflammatory features of the disease (e.g. arthritis, myositis, fibrosing alveolitis).

Both allogeneic and autologous bone marrow transplantation (BMT) have shown to modify and in some instances reverse a variety of animal models of autoimmune disease. This has prompted many investigators to propose the use of peripheral blood stem cell transplantation (PBSCT) for the treatment of autoimmune disease including scleroderma. Unfortunately, this approach risks infusing untreated autoreactive lymphocyte clones after the immunoablative preparative regimen. We have previously demonstrated that high-dose cyclophosphamide without BMT can induce durable and complete remissions in another autoimmune disease, severe aplastic anemia. Recent data with high dose cyclophosphamide show that it can induce complete remissions in other autoimmune hematologic disorders. The objective of this study is to determine whether high dose cyclophosphamide can induce a durable remission in scleroderma patients with life-threatening disease, and to determine toxicity of high dose cyclophosphamide in high risk scleroderma patients.

Inclusion Criteria:

• Meet established criteria for a diagnosis of diffuse cutaneous scleroderma and have evidence of moderately severe organ damage and clinical evidence of active disease.
• Patients with diffuse scleroderma who have evidence of active fibrosing alveolitis manifested by either a greater than 10% decline in the forced vital capacity or the diffusing capacity from the defined normal values or from baseline measurements.
• Patients with severe deforming localized scleroderma (generalized morphea, liner morphea, keloid or bullous scleroderma) that threatens their capacity to function normally in society.

Exclusion Criteria:

• Age less than 18 years and over 70 years
• Any risk of pregnancy
• Cardiac ejection fraction of < 45%
• Serum creatinine > 3.0
• Patients who are pre-terminal or moribund
• Bilirubin > 2.0, transaminases > 2x normal
• FVC, FEV1 (5/30/01) < 50% predicted