Hematopoietic Stem Cell Therapy for Patients With Refractory Myasthenia Gravis

Inclusion Criteria (Patients must fulfill all of the following)

1. Established diagnosis of myasthenia gravis defined as clinical evidence of muscle weakness and fatigue ability and supported, an abnormal EMG-NCV repetitive nerve stimulation (or single-fiber EMG) or Lambert-Eaton Myasthenic Syndrome without evidence of malignancy.
2. Ages 15-65 years.
3. Positive antibody preferred (anti-AchR, MuSK, voltage gated calcium channel, anti-striational).
4. Failure of thymectomy (except for Lambert-Eaton Myasthenic Syndrome).
5. Failure anticholinesterase therapy, corticosteroids, and at least two of the following: azathioprine, cyclosporin, CellCept, cyclophosphamide, plasma exchange, or IVIG. Failure is defined as at least 6 months of the above drug therapy and an Osserman score of IIB, III, or IV and not clinically improving.

And at least one of the following:

1. History of myasthenia crises (requiring mechanical ventilation) despite thymectomy and immunosuppressive therapy.
2. Hospitalized or on ventilator support for myasthenia gravis within the last 18 months despite thymectomy and immunosuppressive therapy.
3. Inability to maintain nutrition due to muscle weakness.
4. A Karnofsky performance status of 70% or less (may or may not be able to care for self, but unable to carry on normal activity or unable to do active work).

Exclusion Criteria

1. Significant end organ damage such as:

   1. LVEF \<40% or deterioration of LVEF during exercise test on MUGA or echocardiogram.
   2. Untreated life-threatening arrhythmia, active ischemic heart disease or heart failure.
   3. DLCO \< 40% of predicted value.
   4. Serum creatinine \> 2.5 mg/dl.
   5. Liver cirrhosis, transaminases \>3x of normal limits, or bilirubin \>2.0 unless due to Gilberts disease.
2. HIV positive.
3. 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.
4. 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.
5. 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.
6. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
7. Inability to give informed consent
8. Congenital myasthenia gravis
9. Neonatal myasthenia gravis
10. Osserman grade 1 or 2
11. Pure red cell aplasia
12. Any patient on insulin