MOST

Treatment tested

• Cyclophosphamide anhydrous
• 2-mercaptoethanesulfonic acid
• rATG
• Methylprednisolone

  Glucocorticoid receptor agonist

• Filgrastim

  Granulocyte colony stimulating factor receptor agonist

• Human immunoglobulin g

  Replacement therapy, immunomodulatory effects

• Autologous Stem Cells

Inclusion Criteria: 1. Age between 18-58 years 2. Diagnosis of MS using revised McDonald criteria of clinically definite MS (Appendix A) 3. An EDSS score of 2.0 to 6.0 (Appendix B). 4. An EDSS >6.0 may be included if still relapsing-remitting disease and at least two enhancing lesions on MRI within the last three months 5. Inflammatory disease despite treatment with standard disease modifying therapy (DMT) including at least 6 months of interferon or Copaxone. Inflammatory disease is defined based on either MRI (gadolinium enhancing lesion, new T2 lesion) or *steroid-treated clinical relapses (prescribed by a neurologist) 6. Minimum disease activity required: 1. Failed a first line DMT (Copaxone or Interferon), defined as two or more *steroid treated clinical relapses within the last 12 months. A clinical relapse may also be evidence of active inflammation on MRI (gadolinium enhancing lesion or new T2 lesion) in the last 12 months on two MRIs at least three months apart 2. Failed a second or third line MS Drug: Zinbryta (daclizumab), Aubagio (teriflunomide), Gilenya (fingolimod), Tecifidera (dimethyl fumarate), Lemtrada (alemtuzumab), Ocrevus (ocrelizumab), Tysabri (natalizumab), Rituxan (rituximab) or IVIg, defined as one *steroid treated clinical relapse within the last 12 months or evidence of active inflammation on MRI (gadolinium enhancing lesion or new T2 lesion) in the last 12 months. 3. Cognitive dysfunction that prevents gainful employment, but competent to comply with treatment and informed consent * A steroid-treated relapse will include a relapse that was severe enough to justify treatment but due to patient intolerance of steroids, they were offered but not used. Exclusion Criteria: 1. Any adult who is unable to consent (for adults who are cognitively impaired due to MS, consent may be obtained from the closest living relative or person who has power of attorney) 2. Individuals under the age of 18 or over the age of 58 3. Diagnosis of Primary Progressive MS, Secondary Progressive MS, or Clinically Isolated Syndrome (CIS) 4. Pregnant women (positive serum or urine human chorionic gonadotropin (HCG) test) 5. Women who are breastfeeding 6. Prisoners 7. Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy 8. Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix 9. Any prior chemotherapy or radiation therapy (except for cyclophosphamide used to treat MS disease) 10. History of sickle cell disease (SS), SC disease, coagulopathy, or if actively receiving anticoagulation therapy 11. History of insulin-dependent diabetes 12. Inability or unwillingness to pursue effective means of birth control from the time of evaluation for eligibility until 6 months post-transplant. Effective birth control is defined as (1) abstinence defined as refraining from all acts of vaginal intercourse, (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 intrauterine device (IUD), or (6) with every act of intercourse, use of diaphragm with contraceptive jelly and/or use of condom with contraceptive foam 13. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy 14. Forced expiratory volume at one second (FEV1)/ forced vital capacity (FVC) \< 60% of predicted after bronchodilator therapy (if necessary) 15. Diffusing capacity of the lungs for carbon monoxide (DLCO) \< 60% of predicted 16. Resting left ventricular ejection fraction (LVEF) \< 50 % 17. Bilirubin > 2.0 mg/dl 18. Serum creatinine > 2.0 mg/dl 19. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins or to iron compounds/medications 20. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams 21. Platelet count \< 100,000/ul 22. White blood cell count (WBC) \< 1,500 cells/mm3 23. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible 24. Active infection except asymptomatic bacteriuria 25. Use of Tysabri (natalizumab) within the previous six months 26. Use of Gilenya (fingolimod) within the previous three months 27. Use of Tecfidera (dimethyl fumarate) within the previous three months 28. Use of Aubagio (teriflunomide) unless cleared from the body (plasma concentration \<0.02mcg/ml) following elimination from the body with cholestyramine 8g three times a day for 11 days 29. Use of Lemtrada/Campath (alemtuzumab) within previous 12 months 30. Use of Rituxan (rituximab) or Ocrevus (ocrelizumab) within previous four months 31. Prior treatment with Novantrone (mitoxantrone) 32. Any hereditary neurological disease such as Charcot-Marie-Tooth disease (CMT), Spinocerebellar ataxia (SCA), or Parkinson's Disease 33. Severe or symptomatic cervical spinal stenosis unless surgically corrected 34. Myocardial infarction within last 12 months; if longer than 12 months, must pass dobutamine stress test and be cleared by cardiology

Randomized study of autologous un-manipulated peripheral blood hematopoietic stem cell transplant (HSCT) comparing two regimens: (1) cyclophosphamide and rabbit anti-thymoglobulin (rATG) versus (2) cyclophosphamide, rATG, and Intravenous Immunoglobulin (IVIg).