A Phase II Study of High-Dose Immunosuppressive Therapy (HDIT) Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) and Thymoglobulin, and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) for the Treatment of Poor Prognosis Multiple Sclerosis

Inclusion Criteria:

- Diagnosis of relapsing-remitting or progressive-relapsing multiple sclerosis for less
than 15 years using McDonald Criteria. More information on this criterion can be
found in the protocol.

- Score between 3.0 and 5.5 on the Expanded Disability Status Scale (EDSS)

- T2 abnormalities on brain MRI consistent with MS

- Two or more relapses in 18 months time on interferon (IFN), glatiramer acetate (GA),
natalizumab or cytotoxic therapy with EDSS increase of 1.0 or greater for
participants with EDSS at screening of 3.0 to 3.5 (0.5 or greater for participants
with EDSS at screening of 4.0 to 5.5) sustained at least 4 weeks after at least one
of these relapses OR one relapse on IFN, GA, natalizumab or cytotoxic therapy with
EDSS increase of 1.5 or greater (1.0 for subjects with EDSS at screening of 5.5)
sustained at least 4 weeks, together with MRI changes consistent with poor prognosis.
More information on this criterion can be found in the protocol.

- On IFN or GA for at least 6 months before the relapses occur that are counted to
satisfy previous inclusion criterion OR have received adequate doses of natalizumab
or cytotoxic therapy on a treatment schedule before the relapses occur that are
counted to satisfy previous inclusion criterion.

- Approval by an MS Review Panel to participate in the study. More information on this
criterion can be found in the protocol.

- In good clinical condition with adequate organ function and without coexisting
medical problems that would increase the risk to the participant

- Willing to use acceptable methods of contraception

- Willing and able to comply with all study requirements

- Willing to accept and comprehend irreversible sterility as side effect of therapy

Exclusion Criteria:

- Primary progressive MS

- Secondary progressive MS without relapses (i.e., progression without exacerbations or
relapses) for 12 or more months

- Neuromyelitis optica, a disease similar to MS

- Initiation of new immunosuppressant treatment after the participant becomes eligible
for the protocol or continuance of immunosuppressant drugs after the participant is
screened for the protocol. Treatment with IFN, GA, or corticosteroids is permitted
after the participant becomes eligible for the protocol.

- Lapse of greater than 6 months between the time a participant is eligible for the
protocol and initiation of protocol treatment except when judged acceptable by the MS
Review Panel

- Prior treatment with investigational immunosuppressive agents within 3 months of
study eligibility

- Positive baseline plasma and CSF testing for JC virus or a brain MRI that has changes
consistent with a diagnosis of progressive multifocal encephalopathy (PML).

- History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS)

- Active hepatitis B or C infection, cirrhosis, or HIV infection

- Uncontrolled diabetes mellitus

- Uncontrolled viral, fungal, or bacterial infection. Patients with asymptomatic
bacteriuria are not excluded.

- Any illness that would jeopardize the ability to tolerate aggressive chemotherapy

- Prior history of malignancy, except localized basal cell or squamous skin cancer.
Other malignancies for which the subject is judged cured by the administered therapy
will be considered on an individual basis.

- Hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins or to iron
compounds/medications

- Metallic objects implanted in the body that would affect MRI exams

- Psychiatric illness, mental deficiency, or cognitive dysfunction

- Pregnancy