DISEASE CHARACTERISTICS:

• Must have severe and active lupus, refractory to immunosuppressive therapy, defined as 1 of the following:

  • Nephritis: Biopsy-proven diffuse proliferative glomerulonephritis (WHO class IV) with or without superimposed membranous changes

    • Active disease, meeting 1 of the following criteria:

      • A kidney biopsy within 3 months of enrollment showing active WHO class IV disease (based on the presence of endocapillary cellular proliferation compromising the capillary loops or cellular crescents or necrosis on light microscopy or subendothelial deposits on electron microscopy)
      • If a biopsy is contraindicated, patients are eligible if they had a previous biopsy showing diffuse proliferative glomerulonephritis (WHO class IV) AND meeting all of the criteria (at the time of enrollment): proteinuria > 1 g/day; active urine sediment defined as hematuria (> 10 RBC/high-power field on a nephrology urinalysis of a 50-mL urine sample) with dysmorphic RBC and/or cellular casts on a nephrology urinalysis of a 50-mL urine sample; and low C3 (< 69 mg/dL) and/or elevated dsDNA antibodies (> 25 EU)
      • Requires > 20 mg/day of prednisone due to increased renal activity after at least 6 months of cyclophosphamide

    • Treatment-resistant disease, meeting 1 of the following criteria:

      • Active disease after at least 6 months of mycophenolate mofetil or IV pulse cyclophosphamide with or without IV methylprednisolone and daily oral prednisone
      • Early flare defined as patients who have reactivation of their nephritis during or within 6 months of completing cyclophosphamide therapy
      • Recalcitrant disease defined as 2 or more recurrences of lupus nephritis within 5 years of enrollment (all flares must have received adequate therapy and at least 1 of the episodes must have been treated with a minimum of 6 months of IV pulse cyclophosphamide with or without IV methylprednisolone and maintenance oral prednisone)

  • CNS lupus: Lupus CNS manifestations indicative of encephalitis, myelitis, or vasculitis (clinical signs and symptoms must be supported by objective findings of CNS inflammation)

    • Active disease, meeting 1 of the following criteria:

      • Any of the signs and symptoms: clinical signs and symptoms compatible with focal CNS damage; severe global neurocognitive/psychiatric impairment (e.g., psychosis, organic brain syndrome, or severe depression); or intractable seizures
      • Clinical findings supported by at least 1 of the following: MRI findings consistent with transverse myelitis or CNS vasculitis (signs of inflammation on MRI are either the presence of gadolinium-enhancing lesions or the increase in the number and/or volume of T2-weighted lesions [or lesions showing up on FLAIR imaging]); if the patient has seizures/psychiatric signs and symptoms in the absence of clear signs of vasculitis or cerebritis by MRI, the CSF protein shows elevation above normal levels and an abnormal number of WBCs or intrathecal IgG synthesis/or oligoclonal bands; or requires > 20 mg/day of prednisone due to increased CNS activity after at least 3 months of cyclophosphamide therapy

    • Treatment-resistant disease, meeting 1 of the following criteria:

      • Active disease after at least 3 months of oral or IV cyclophosphamide
      • Early flare defined as reactivation of CNS lupus within 6 months of completing cyclophosphamide therapy
      • Recalcitrant disease defined as 2 or more recurrences of CNS lupus within 5 years of enrollment (all flares must have received adequate therapy and at least 1 of the episodes must have been treated with a minimum of 3 months of oral or IV cyclophosphamide)

  • Pulmonary lupus

    • Active disease, meeting 1 of the following criteria:

      • Lung biopsy showing active pneumonitis, alveolitis, or pulmonary vasculitis after the minimally required therapy within 1 month of enrollment
      • If a biopsy is contraindicated within 1 month of enrollment, patients may be included if they had a biopsy at the start of or during cyclophosphamide treatment showing active pneumonitis, alveolitis, or pulmonary vasculitis; have abnormal or worsening pulmonary function tests with a chest CT consistent with active pneumonitis, alveolitis, or vasculitis within 2 weeks of enrollment; and, at the time of enrollment, have a CT consistent with active disease
      • Requires > 20 mg/day of prednisone due to increased pulmonary lupus activity after at least 3 months of cyclophosphamide

    • Treatment-resistant disease, meeting 1 of the following criteria:

      • Ongoing or recurrent active pulmonary lupus after at least 3 months of oral or IV cyclophosphamide
      • Early flare defined as reactivation of pulmonary lupus within 6 months of completing cyclophosphamide therapy
      • Recalcitrant disease defined as 2 or more recurrences of pulmonary lupus within 5 years of enrollment (all flares must have received adequate therapy and at least 1 of the episodes must have been treated with a minimum of 3 months of oral or IV cyclophosphamide)

  • Hematologic disease

    • Active disease, meeting 1 of the following criteria:

      • Severe immune-mediated thrombocytopenia (platelet count < 20,000/mm³ OR < 50,000/mm³ with a history of bleeding)
      • Severe immune-mediated anemia (requiring transfusions to maintain hemoglobin > 8.0 g/dL OR to treat symptoms of anemia)
      • Requires > 20 mg/day of prednisone due to increased hematologic lupus activity after therapy

    • Treatment-resistant disease, meeting 1 of the following criteria:

      • Active disease after at least 3 months of high-dose oral or pulse corticosteroids with or without IV immunoglobulin (or WinRho) and splenectomy
      • Early flare defined as reactivation of hematologic lupus within 6 months of completing therapy
      • Recalcitrant disease defined as 2 or more recurrences of immune-mediated thrombocytopenia or anemia within 5 years of enrollment (all flares must have received adequate therapy and at least 1 of the episodes must have been treated by splenectomy)

• Must meet at least 4 of the following criteria for systemic lupus erythematosus (SLE), as defined by the American College of Rheumatology:

  • Malar rash
  • Discoid rash
  • Photosensitivity
  • Oral ulcers
  • Arthritis

  • Serositis, meeting 1 of the following criteria:

    • Pleuritis

      • Convincing history of pleuritic pain, rub heard by a physician, or evidence of pleural effusion

    • Pericarditis

      • Documented by ECG or rub or evidence of pericardial effusion

  • Renal disorder, meeting 1 of the following criteria:

    • Persistent proteinuria > 0.5 g/day OR > 3+ if quantitation not performed

    • Cellular casts, meeting any of the following types:

      • Red cell
      • Hemoglobin
      • Granular
      • Tubular
      • Mixed

  • Neurologic disorder, meeting 1 of the following criteria:

    • Seizures in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, or electrolyte imbalance)
    • Psychosis in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, or electrolyte imbalance)

  • Hematologic disorder, meeting 1 of the following criteria:

    • Hemolytic anemia with reticulocytosis
    • Leukopenia (less than 4,000/µL total on 2 or more occasions)
    • Lymphopenia (less than 1,500/μL on 2 or more occasions)
    • Thrombocytopenia (less than 100,000/µL in the absence of offending drugs)

  • Immunologic disorder, meeting 1 of the following criteria:

    • Antibody to native DNA in abnormal titer
    • Presence of antibody to SM nuclear antigen

    • Positive finding of antiphospholipid antibodies based on 1 of the following:

      • An abnormal serum level of IgG or IgM anti-cardiolipin antibodies
      • A positive test result for lupus anticoagulant using a standard method
      • A false-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test
    • An abnormal titer of antinuclear antibodies by immunofluorescence or an equivalent assay at any point in time in the absence of drugs known to be associated with "drug-induced lupus" syndrome

• No late flare

  • Patients who have a single episode of target organ flare, that is not within the time frame defined as early flare, will not be considered as treatment failures until they receive the minimally required therapy for this flare episode and fail to respond to it
• No abnormal bone marrow cytogenetics
• No concurrent CNS diseases (e.g., infections, multiple sclerosis [MS], and patients fulfilling MS and SLE criteria)

PATIENT CHARACTERISTICS:

• SGOT or SGPT ≤ 2 times upper limit of normal (ULN) (unless active myopathy is proven by elevation of serum aldolase levels and the patient has no obvious hepatic disease)
• Bilirubin ≤ 2.0 times ULN (unless due to isolated hemolysis)
• Glomerular filtration rate ≥ 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 years (females) or 6 months (males) after completion of study therapy
• No DLCO corrected < 45%
• No LVEF < 45%, determined by ECHO cardiogram or MUGA scan
• No evidence of hepatitis B or C infection
• No evidence of HIV infection
• No history of malignancy except for basal cell carcinoma of the skin
• No significant concurrent medical condition or any significant circumstance that could affect the patient's ability to tolerate or complete the study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior live vaccines
• At least 3 weeks since prior pulse cyclophosphamide
• At least 2 weeks since prior antimalarials
• At least 1 week since prior methotrexate, mycophenolate mofetil, azathioprine, oral daily cyclophosphamide, leflunomide, cyclosporine, or any other medication for lupus

• All immunosuppressive and disease-modifying treatments must be discontinued before study therapy

  • Steroids and analgesics (except for NSAIDS), including narcotics, are allowed