OBJECTIVES: I. Determine the safety of immune ablation with high-dose cyclophosphamide and anti-thymocyte globulin followed by peripheral blood stem cell support in patients with systemic lupus erythematosus.

PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 1 hour for 2 doses. Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 24 hours after completion of cyclophosphamide and continuing until leukapheresis is complete. Leukapheresis continues daily until target number of cells is harvested. CD 34+ cells are isolated from peripheral blood stem cells (PBSC) in vitro. Patients then receive cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV over 10 hours on days -4 to -2, and G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients undergo reinfusion of CD34+ PBSC on day 0. Patients are followed weekly for 90 days, monthly for 1 year, and at 2 years.

Ages Eligible for Study:  up to  59 Years,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of systemic lupus erythematosus with 1 of the following malignant features:

• Nephritis (WHO class III or IV)
• Failed NIH short-course cyclophosphamide therapy
• Vasculitis/immune complex deposition causing end organ signs or symptoms (e.g., cerebritis, transverse myelitis, pulmonary hemorrhage, cardiac failure, or renal failure)
• Hematologic cytopenias that are immune mediated and uncontrolled by conservative measures with any of the following:

Transfusion-dependent anemia with untransfused hemoglobin less than 8 g/dL

Platelet count less than 40,000/mm3 (without transfusions)

Granulocyte count less than 1,000/mm3

Catastrophic anti-phospholipid syndrome

--Patient Characteristics--

Cardiovascular:

• LVEF at least 35%
• No lupus-induced myocarditis
• No history of unstable angina

Pulmonary:

• FEV1/FVC at least 50% predicted
• DLCO at least 50% predicted

Other:

• HIV negative
• No prior or concurrent malignancy except localized basal cell or squamous cell skin cancer
• No uncontrolled diabetes mellitus
• No medical illness that would preclude study
• No psychiatric illness or mental deficiency that would preclude study
• No known hypersensitivity to E. coli-derived proteins
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception