Inclusion Criteria:

1. Age between18-55, inclusive.
2. Diagnosis of MS using McDonald criteria of clinically definite MS (Appendix I).
3. An EDSS of 2.0 to 6.0 (Appendix II).
4. Inflammatory disease despite treatment with standard disease modifying therapy including at least 6 months of interferon or copaxone. Inflammatory disease is defined based on both MRI (gadolinium enhancing lesions) and clinical activity (acute relapses *treated with IV high dose corticosteroids). Minimum disease activity required for failure is defined as: a) two or more clinical relapses with documented neurologic changes within the year prior to the study, or b) one *steroid treated clinical relapse within the year prior to study and evidence on MRI of active inflammation (i.e., gadolinium enhancement) within the last 12 months on an occasion separate from the clinical relapse (3 months before or after the clinical relapse). *A steroid treated relapse will include a relapse that was severe enough to justify treatment but due to patient intolerance of steroids, or a history of non-response to steroids, they were offered but not used.

Exclusion criteria:

1. Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy.
2. Prior therapy with mitoxantrone
3. Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix. Other malignancies for which the patient is judged to be cured, such as head and neck cancer, or breast cancer will be considered on an individual basis.
4. Positive pregnancy test.
5. Inability or unwillingness to pursue effective means of birth control. Effective birth control is defined as 1) refraining from all acts of vaginal intercourse (ABSTINENCE); 2) consistent use of birth control pills; 3) injectable birth control methods (Depo-provera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an IUD (intrauterine device); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam.
6. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
7. FEV1/FVC < 60% of predicted after bronchodilator therapy (if necessary).
8. DLCO < 50% of predicted (for the transplant arm).
9. Resting LVEF < 50 %.
10. Bilirubin > 2.0 mg/dl.
11. Serum creatinine > 2.0 mg/dl.
12. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications.
13. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams.
14. Diagnosis of primary progressive MS.
15. Diagnosis of secondary progressive MS
16. Platelet count < 100,000/ul, WBC < 1,500 cells/mm3.
17. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible.
18. Active infection except asymptomatic bacteriuria.
19. Use of natalizumab within the previous 6 months.