Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG)/Rituximab in Patients With Systemic Lupus Erythematosus

Mobilization Participants will be administered Cyclophosphamide at 2.0 g/m2 in 200 ml of
normal saline (NS) over 1 hour. Hydration with 0.9 NS at approximately 100-250-ml/ hour will
begin 4 hours prior to cyclophosphamide and continued for 24 hours after termination of
cyclophosphamide. Urine output approximately greater than 100 ml/hour should be maintained.

Granulocyte-colony stimulating factor (G-CSF) will be administered subcutaneously at 5-10
mcg/kg/day and will be started 5 days after termination of cyclophosphamide administration.

After the absolute neutrophil count is greater than 1000/ul or after hematological nadir,
leukapheresis using a continuous flow blood cell separator will be initiated. A 10-15 liter
apheresis will be performed unless stopped earlier for clinical judgment of toxicity (e.g.,
numbness, tetany). The G-CSF will continue until apheresis is discontinued. If necessary,
platelets will be transfused to greater than 60,000/ul prior to each apheresis.

Conditioning Regimen Mesna: 50mg/kg/day x 4 days will be given intravenously over 24 hours.

Cyclophosphamide: 50 mg/kg/day x 4 days (the lesser of ideal or actual weight) will be given
intravenously over 1 hour in 250 cc of normal saline on days -5 through -2.

Hydration: approximately 50-200cc/hour in adults should begin 6 hours before cyclophosphamide
and continue until 24 hours after the last cyclophosphamide dose. Hydration rates need to be
individually adjusted by daily weights to maintain dry weight count. Twice daily weights will
be obtained. Warning: Participants with renal insufficiency are prone to volume overload.
Early institution of ultrafiltration or dialysis is recommended.

rATG 0.5mg/kg will be given IV on day -5, 1.0mg/kg will be given on day

-4, 1.5mg/kg will be given IV on days -3, -2, -1 (no dose adjustment). It will be given over
10 hours. Premedicate with Solumedrol 250mg IV, acetaminophen 650mg po qd and diphenhydramine
25mg 30 minutes before infusion.

Rituximab 500mg/day will be given IV on days -6 and +1. At the first dose (D-6), rituximab
infusion will be started at 50mg/h and escalate the infusion rate by 50mg every 30minutes to
a maximum of 400mg/h. Starting the second dose (days -4, -2 and +1). IV infusion will be
started at 100mg/h and escalate the infusion rate 100mg every 30minutes to a maximum of
400mg/h. Premedicate with Solumedrol 250mg IV, acetaminophen 650mg po qd and diphenhydramine
25mg 30 minutes before infusion on days -6 and +1. Premedicate acetaminophen 650mg po qd and
diphenhydramine 25mg 30 minutes before infusion on days -4 and -2.

Stem Cell Reinfusion Previously collected stem cells will be reinfused on day 0 as noted in
Table 4. The stem cells are infused over approximately 20 minutes through the central venous
catheter, such as a peripherally inserted central catheter (PICC line). Following stem cell
reinfusion, routine daily labs will be obtained including complete blood count (CBC),
chemistry panel, and liver function tests. Antibiotics and blood transfusions will be
administered as required by clinical judgment.

Inclusion Criteria:

- Ages 15 to 60 years old

- Meet at least 4 of 11 American College of Rheumatology (ACR) Classification criteria
for systemic lupus erythematosus (SLE) (see Appendix 16.2)

- Meet one of following five:

1. For lupus nephritis, participants must fail pulse cyclophosphamide (500 to 1000
mg/m2 monthly for a minimum of 6 months). Failure is defined as meeting criteria
to be considered as BILAG renal category A.

2. For visceral organ involvement other than nephritis, participants must be BILAG
cardiovascular/respiratory category A, vasculitis category A, or neurologic
category A and must fail at least 3 months of oral or IV cyclophosphamide and be
corticosteroid dependent. Steroid dependence being defined as at least 3 months
of steroid therapy and inability to wean corticosteroid to less than 20 mg/day of
prednisone or equivalent.

3. For cytopenias that are immune mediated, participants must be BILAG hematologic
category A. Participants must fail corticosteroids (either oral prednisone > 0.5
mg/kg/day for more than 6 months or pulse methylprednisolone for at least one
cycle of three days), and at least one of the following: azathioprine at 2
mg/kg/day for at least 3 months, mycophenolate mofetil 2 grams daily for more
than 3 months, cyclophosphamide intravenously or orally for at least 3 months, or
cyclosporine at least 3 mg/kg/day for at least 3 months, danazol for at least 3
months, or splenectomy.

4. For mucocutaneous disease, participants must meet BILAG mucocutaneous category A,
be unable to be weaned from prednisone to less than 0.5 mg/kg/day for more than 6
months and obvious cushingoid habitus, and have received at least one of the
following: azathioprine at 2 mg/kg/day for at least 3 months, methotrexate at
15mg/week for at least 3 months, cyclophosphamide intravenously or orally for at
least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months.

5. For arthritis/myositis, participants must meet BILAG musculoskeletal category A,
be unable to be weaned from prednisone to less than 0.5 mg/kg/day for more than 6
months and obvious cushingoid habitus, and have received at least one of the
following: azathioprine at 2 mg/kg/day for at least 3 months, methotrexate at
15mg/ week for at least 3 months, cyclophosphamide intravenously or orally for at
least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months.

- Able to give informed consent.

- If indication for hematopoietic stem cell transplant (HSCT) is nephritis, a renal
biopsy must demonstrate the potential of a reversible (non-fibrotic) component
indicating that if successful the participant would not be likely to be permanently
dialysis-dependent after transplant.

- Since the BILAG is only one of multiple indices for SLE, patients may also be
candidates if despite prior immune suppression therapy as described above, patients
are still on active immune suppression (more than 10mg a day of prednisone).

- Patients with SLE whose major manifestation is Antiphospholipid syndrome (APS) may be
candidates without prior immune suppression therapy if they have had a visceral organ
thrombotic or embolic event despite anticoagulation.

- Patients with SLE whose major manifestation is Antiphospholipid syndrome (APS) may be
candidates without prior immune suppression therapy if they have had a visceral organ
thrombotic or embolic event despite anticoagulation.

Exclusion Criteria:

- HIV positive

- Ongoing malignancy except localized basal cell or squamous skin cancer. Other
malignancies for which the participant is judged to be cured by local surgical
therapy, such as head and neck cancer, or stage I or II breast cancer will be
considered on an individual basis by the investigators doing the final screening for
participant qualification.

- Positive pregnancy test, inability or unwillingness to pursue effective means of birth
control, failure to willingly accept or comprehend irreversible sterility as a side
effect of therapy.

- Psychiatric illness or mental deficiency making compliance with treatment or informed
consent impossible.

- Diffusing capacity of lung for carbon monoxide (DLCO) < 45% of predicted unless
attributed to active lupus.

- Resting left ventricular ejection fraction (LVEF) < 40% unless attributed to active
lupus.

- Known hypersensitivity to E Coli derived proteins.

- Transaminases greater than 2 times normal unless attributed to active lupus.

- Positive tuberculosis skin test

- Any active infection

- Any co-morbid illness that in the opinion of the investigator would jeopardize the
ability of the subject to tolerate the study.

- Failure to collect at least 2.0 x 106 cluster of differentiation 34 (CD34+) cells/kg

- Antinuclear antibody (ANA)-negative