Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases

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, 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.
10. Failure to collect at least 2.0 x 106 CD34+ cells by apheresis and, if necessary, bone marrow harvest is a contraindication to treatment, i.e., receiving the conditioning regimen.