Inclusion Criteria

-INCLUSION CRITERIA

1. Age 15-40 years

2. Must fulfill at least 4 of the following 11 criteria for SLE as defined by the
American College of Rheumatology:

-Malar rash. Fixed erythema, flat or raised, over the malar eminences, tending to
spare the nasolabial folds.

- Discoid rash. Erythematous raised patches with adherent keratotic scaling and
follicular plugging; atrophic scarring may occur in older lesions.

- Photosensitivity. Skin rash as a result of unusual reaction to sunlight, by
patient history or physician observation.

- Oral ulcers. Oral or nasopharyngeal ulcerations, usually painless, observed by
a physician.

- Arthritis. Nonerosive arthritis involving two or more peripheral joints,
characterized by tenderness, swelling, or effusion.

- Serositis. a.) Pleuritis - convincing history of pleuritic pain or rub heard by
a physician or evidence of pleural effusion

OR

b.) Pericarditis - documented by ECG or rub or evidence of pericardial effusion

-Renal disorder. a.) Persistent proteinuria greater than 0.5 grams per day or
greater than 3+ if quantitation not performed

OR

b.) Cellular casts - may be red cell, hemoglobin, granular, tubular, or mixed.

- Neurologic disorder. a.) Seizures - in the absence of offending drugs or known
metabolic derangements; eg, uremia, ketoacidosis, or electrolyte imbalance

OR

b.) Psychosis - in the absence of offending drugs or known metabolic derangements;
eg, uremia, ketoacidosis, or electrolyte imbalance

-Hematologic disorder. a.) Hemolytic anemia - with reticulocytosis

OR

b.) Leukopenia - less than 4000/ L total on two or more occasions

OR

c.) Lymphopenia - less than 1500/ L on two or more occasions

OR

d.) Thrombocytopenia - less than 100,000/ L in the absence of offending drugs

- Immunologic disorder. a.) Anti-DNA: antibody to native DNA in abnormal titer

OR

b.) Anti-SM: presence of antibody to SM nuclear antigen

OR

c.) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum
level of IgG or IgM anti-cardiolipin antibodies, (2) a positive test result for lupus
anticoagulant using a standard method, or (3) 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

-Antinuclear antibodies. An abnormal titer of ANAs 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.

3. Have severe and active lupus, refractory to immunosuppressive therapy, defined as one
of the following (a-d):

a.Nephritis: Biopsy proven Diffuse Proliferative Glomerulonephritis (WHO Class IV)
with or without superimposed membranous changes

i.Active disease:

1. A kidney biopsy within three months of enrollment showing active WHO Class IV
disease. Activity will be determined 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.

2. If a biopsy is contraindicated patients can be enrolled if they had a previous biopsy
showing Diffuse Proliferative Glomerulonephritis (WHO Class IV) and at the time of
enrollment have all of the following:

1. Proteinuria greater than 1gm/day

2. Active urine sediment defined as hematuria (greater than 10 RBC/hpf 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

3. Low C3 (less than 69 mg/dL) and/or elevated dsDNA antibodies (greater than 25EU)

3. Need for prednisone greater than 20 mg/day due to increased renal activity after at
least 6 months of cyclophosphamide.

ii. Treatment resistant:

1. Patients with active disease after at least 6 months of intravenous pulse
cyclophosphamide +/- iv methylprednisolone and daily oral prednisone, or

2. Early flare: those who have reactivation of their nephritis during or within 6 months
of completing cyclophosphamide therapy

3. recalcitrant disease: two or more recurrences of lupus nephritis within five years of
enrollment. All flares must have received adequate therapy and least one of the
episodes must have been treated with minimun 6 months of intravenous pulse
cyclophosphamide plus iv methylprednisolone and maintenance oral prednisone.

CNS lupus: Lupus CNS manifestations indicative of encephalitis or myelitis or
vasculitis. Concomitant CNS diseases should be excluded. (e.g. infections, multiple
sclerosis; patients fulfilling MS and SLE criteria will be excluded). Clinical signs
and symptoms must be supported by objective findings of CNS inflammation.

i. Active disease:

Signs/symptoms that are accepted for disease activity:

-Clinical signs and symptoms compatible with focal CNS damage -Severe global
neurocognitive/psychiatric impairment (eg: psychosis, organic brain syndrome, severe
depression)

-Intractable seizures

Clinical findings must be supported by at least one of the following:

1. MRI findings consistent with transverse myelitis or

CNS vasculitis

- Signs of inflammation on MRI are either the presence of Gadolinium
(Gd)-enhancing lesions, or the increase of the number and/or volume of
T2-weighted lesions (or lesions showing up on FLAIR imaging). We will use the
standard MS protocol sequences, which are routinely used in the Clinical Center
to evaluate inflammatory CNS lesions.

2. If patient has seizures/psychiatric signs and symptoms in the absence of clear
signs of vasculitis or cerebritis by MRI, the CSF should show protein elevation
above normal levels and abnormal number of WBCs or intrathecal IgG synthesis/or
oligoclonal bands.

3. Need for prednisone greater than 20 mg/day due to increased CNS activity (see
above) after at least three months of cyclophosphamide therapy.

ii-Treatment resistant:

a) Active disease after a minimum of three months of oral or intravenous
cyclophosphamide, or

b) Early flare: reactivation of CNS lupus within 6 months of completing
cyclophosphamide therapy

c. Recalctrant disease: two or more recurrences of CNS lupus within five years of
enrollment. All flares must have received adequate therapy and at least one of the
episodes must have been treated with minimun three months of oral or intravenous
cyclophosphamide.

Pulmonary lupus

i. Active disease:

1. Lung biopsy showing active pneumonitis, alveolitis or pulmonary vasculitis
after the minimally required therapy within one month of enrollment or

2. If a biopsy is contraindicated within one month of enrollment, patients may be
included if they had a biopsy at the start or during cyclophosphamide treatment
showing active pneumonitis, alveolitis or pulmonary vasculitis (as above) and
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.

3. Need for prednisone greater than 20 mg/day due to increased pulmonary lupus
activity after minimum of three months of cyclophophamide.

ii. Treatment resistant:

4. Ongoing or recurrent active pulmonary lupus after a minimum of three months of
oral or intravenous cylophosphamide, or

5. Early flare: reactivation of pulmonary lupus (as defined above) within 6 months
of completing cyclophosphamide therapy.

6. Recalcitrant disease: two or more recurrences of pulmonary as described above
within five years of enrollment. All flares must have received adequate therapy
and at least one of the episodes must have been treated with minimum 3 months of
oral or intravenous cyclophosphamide.

i) Active disease:

a) Severe immune-mediated thrombocytopenia (platelet count less than 20,000/mm3 or
less than 50,000/mm3 with history of bleeding), or

b) Severe immune-mediated anemia (requiring transfusions to maintain Hb greater than
8.0 g/dL or to treat symptoms of anemia) c) Need for prednisone greater than 20
mg/day due to increased hematologic lupus activity after therapy as described in
section ii.a).

ii) Treatment resistant:

a) Active disease as defined above after a minimum of three months of high dose oral
or pulse corticosteroids +/- IVIg (or WinRho) and splenectomy, or

b) Early flare: reactivation of hematologic lupus (as defined above) within 6 months
of completing above therapy.

c) Recalcitrant disease: two or more recurrences of immune-mediated thrombocytopenia
or anemia, as described above, within five years of enrollment. All flares must have
received adequate therapy and at least one of the episodes must have been treated by
splenectomy.

EXCLUSION CRITERIA

1. Inability to provide written informed consent prior to entry in the protocol

2. Pregnant or lactating women. Women of childbearing potential are required to have a
negative pregnancy test at screening

3. Women of childbearing potential who are not practicing or who are unwilling to practice
birth control during the entire study

4. Men who are unwilling to practice birth control for the first 6 months after the
transplant

5. Evidence of infection with hepatitis B, hepatitis C, or HIV

6. History of malignancy other than basal cell carcinoma of the skin

7. DLCO corrected less than 45%

8. LVEF less than 45%, determined by ECHO cardiogram or MUGA

9. SGOT or SGPT greater than 2x upper limit of normal (unless active myopathy is proven by
elevation of serum aldolase levels and the patient has no obvious hepatic disease) and/or
bilirubin greater than 2.0 (unless due to isolated hemolysis).

10. Calculated glomerular filtration rate less than 30 ml/min using the MDRD equation
estimate:

GFR (ml/min/173 m(2)) =186.3 x (Pcr) exponential -1.154 x (age) exponential -0.203 x
1.212 (if black) x 0.742 (if female)

11. Late flare (patients who have 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)

12. Abnormal bone marrow cytogenetics

13. Significant concurrent medical condition or any significant circumstance that could
affect the patient's ability to tolerate or complete the study

14. Live vaccines within 4 weeks of starting the priming regimen