Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases

Conditioning Regimen (In order to assure sterility testing, a minimum of 14 days will be
required between stem cell collection and starting the conditioning regimen).

The conditioning regimen is outlined in below:

Cyclophosphamide 50 mg/kg/day will be given IV over 1 hour in 250 cc of normal saline on day
-5, -4, -3, and -2. If actual weight is < ideal weight, cyclophosphamide will be given based
on actual weight. If actual weight is > ideal weight, cyclophosphamide will be given as
adjusted ideal weight. Adjusted ideal weight = ideal weight + 40% (actual weight minus ideal
weight).

Mesna 50mg/kg/day will be given IV over 24 hours in 250 cc of normal saline or D5W starting
at 10AM each dose. Weight base is calculated same as cyclophosphamide as above.

1ATG (rabbit) 0.5 mg/kg on day -6 and 1mg/kg on day -5, -4, -3, -2 and -1 (total 5.5mg/kg, no
dose adjustment) will be given IV over 10 hours in 250 cc of normal saline beginning at least
1 hour after infusion of cyclophosphamide. Premedicate with acetaminophen 650 mg po and
diphenhydramine 25 mg po/IV 30 minutes before the infusion.

Methylprednisolone- A suggested dose of 250mg IV should be administered 30 minutes before
each ATG infusion.

Hydration- A suggested rate of 125 cc/hr NS should be given starting 6 hours before the first
cyclophosphamide dose and continued until 24 hours after the last cyclophosphamide dose. The
rate of hydration will be aggressively adjusted. BID weights will be obtained. Amount of
fluid can be modified based on patient's fluid status. Minimum target urine output is 2
liters/m2/day

G-CSF 5 mcg/kg/day will be given subcutaneously and continued until the absolute neutrophil
counts reaches at least 500/µl.

Rituxan 500 mg will be given IV on the day before the first dose of ATG and the day after
stem cell infusion.

Inclusion Criteria:

1. Age ≥ 16 years and ≤ 65 years at the time of pretransplant evaluation.

2. An established diagnosis of polymyositis, dermatomyositis, juvenile
polymyositis/dermatomyositis, and myositis associated with other collagen diseases.
Diagnosis requires electrophysiological studies and histopathologic features. MRI
evidence of muscle inflammation or histological evidence of active myositis is
mandatory at entry. If patient had dermatomyositis/polymyositis associated with
malignancy, the patient has to be free of malignancy for 5 years and considered to be
cured.

3. Patients who failed conventional treatment of at least 3 months duration including
high-dose corticosteroids (equivalent dosage of prednisone >1.0 mg/kg/day to start),
and must also have failed two or more of the followings: cyclophosphamide,
azathioprine, 6-MP, methotrexate, tacrolimus, cyclosporin A, mycophenolate mofetil,
TNF inhibitor (e.g. etanercept), IVIG or any other immunosuppressive drugs or immune
modulating drugs.

4. Failure is defined by (one or more of the following) (not caused by unrelated
conditions):

- Persistent muscle weakness (grade 4/5 or worse by MRC) with elevation of muscle
derived enzymes (CPK, aldolase)

- Worsening pulmonary function especially %VC or DLCo > 15% over 12 months
indicating active alveolitis.

- Abnormal EKG or echocardiographic evidence of cardiomyopathy.

- Presence of progressive joint contracture, progressive calcinosis, vasculitis, or
skin ulcers in juvenile dermatomyositis/polymyositis.

Exclusion Criteria:

1. Poor performance (PS) status (ECOG >2) at the time of entry, unless decline of PS is
due to the disease itself.

2. Significant end organ damage such as (not caused by IIM):

- LVEF <40% or deterioration of LVEF during exercise test on MUGA or
echocardiogram.

- Untreated life-threatening arrhythmia.

- Active ischemic heart disease or heart failure.

- DLCo <40% or FEV1/FEV < 50%.

- Serum creatinine >2.5 or creatinine clearance <30ml/min.

- Liver cirrhosis, transaminases >3x of normal limits or bilirubin >2.0 unless due
to Gilbert disease.

3. HIV positive.

4. Uncontrolled diabetes mellitus, or any other illness that in the opinion of the
investigators would jeopardize the ability of the patient to tolerate aggressive
treatment.

5. Prior history of malignancy except localized basal cell or squamous skin cancer. Other
malignancies for which the patient is judged to be cured by local surgical therapy,
such as (but not limited to) head and neck cancer, or stage I or II breast cancer will
be considered on an individual basis.

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

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

8. Inability to give informed consent.

9. Major hematological abnormalities such as platelet count less than 100,000/ul, ANC
less than 1000/ul.