Inclusion Criteria:

Criteria for patient selection will be based upon the recent recommendations for clinical
research standards by the Task Force of the Medical Scientific Advisory Board of the
Myasthenia Gravis Foundation of America (Jaretzki et al, 2000).

Patients will be included in the trial based upon fulfilling all the criteria given below,
except that they will be required to fulfill criterion 3 OR 4:

1. Patients must have a diagnosis of "Definite" MG (Seybold, 1999) as based on clinical,
electrophysiological and serological criteria (Appendix 1)

2. Patients must have disease predominantly affecting bulbar or respiratory muscles of
moderate or severe degree (Osserman grades 2B, 3 without crisis, or 4 without crisis)
(Osserman and Genkins, 1971 and Appendix 2) as listed in Appendix 3, and a
Quantitative MG score of <25 (Appendix 7)

3. Patients must have disease refractory to treatment for at least 12 months with
prednisone at a dose of 15mg/day and/or immunosuppressive drugs (azathioprine or
cyclophosphamide at a dose of 100mg/day or cyclosporine at a dose to produce trough
levels of >50), with or without thymectomy and plasmapheresis/IVIG alone or in
combination with above drugs at intervals of no more than once every 3 weeks, OR

4. Patients must have experienced intolerance or unacceptable side-effects following
treatment with corticosteroids, immunosuppressive drugs (azathioprine,
cyclophosphamide or cyclosporine), plasmapheresis or IVIG

5. Patients must be between 18 years and 80 years old

6. Patients must have adequate organ function / laboratory parameters as measured by the
following criteria (values should be obtained within 2 weeks prior to enrollment):

- Documented CD20 + cells

- Absolute neutrophil count: >2000/mm3

- Platelets: >100,000/mm3

- Hemoglobin: >10 gm/dL

- Adequate renal function as indicated by normal BUN and creatinine levels

- Adequate liver function, as indicated by AST and ALT <2x Upper Limit of normal.

- Normal serum electrolytes

7. Men and women of reproductive potential must agree to use an acceptable method of
birth control during treatment and for one year after completion of treatment

8. Written informed consent.

Exclusion Criteria:

Patients will be excluded from the trial based on the following criteria:

1. Myasthenic crisis with a forced vital capacity (FVC) of <30% predicted, irrespective
of need for respiratory support, or severe bulbar involvement (Appendix 3)

2. Patients requiring maintenance plasmapheresis or IVIG infusions at intervals of less
than once every three weeks

3. Patients requiring respiratory support with invasive or non-invasive ventilation

4. Severe, uncontrolled or untreated concomitant cardiac (New York Heart Classification
III or IV disease), hepatic, pulmonary, renal, hematologic or psychiatric disease

5. Toxicity grade 2 or more prior to treatment with rituximab in patients who failed
prior treatments

6. Patients unwilling to attend for follow-up visits according to the study design

7. Patients will be excluded based on the following criteria:

- History of HIV disease

- Active Hepatitis B infection

- Pregnancy (a serum pregnancy test will be performed for all women of
childbearing potential immediately before treatment)

- Active infection

8. Pregnant or breastfeeding women may not participate due to the lack of information on
effects of rituximab on the fetus and developing child

9. Concomitant malignancies or previous malignancies within the last 5 years, with the
exception of adequately treated basal or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix.

10. No prior monoclonal antibody therapy.

11. History of significant psychiatric disease that will interfere with the consenting
procedure, research visits, treatment protocol or evaluation of patients in the
study.