• PASAT 25-foot walk 9-hole peg test [ Time Frame: pre-transplant, 6mo, 12mo, yearly for 5 years ] [ Designated as safety issue: Yes ]
  

• Self-administered quality of life exams (FACT-BMT and SF-36) [ Time Frame: pre-transplant, 6mo, 12mo, yearly for 5 years ] [ Designated as safety issue: Yes ]
  

Procedure: Hematopoietic stem cell transplantation

Mobilization

G-CSF- guidelines, 5-10 mcg/kg/day will be started day +5 and continued until the absolute neutrophil counts reaches at least 1,000

Cytoxan dose of 2gm/m will be infused over two hours.

Mesna, given the dose of 2.0 gm/m, infusion to be given over 24 hours.

Transplant Conditioning Regimen

Cyclophosphamide 50 mg/kg/day will be given IV over 2 hours in 500 cc of normal saline.

r ATG 0.5 mg/kg given on day -5, then 1.0 mg/kg given on day -4, then 1.5 mg/kg given on days -3 through -1.

Rituxan ( Rituximab ) - The dose of 500 mg of Rituximab will be given on days -6 and on day + 1.

G-CSF - guidelines, 5-10 mcg/kg/day will be started day + 5 and continued until the absolute neutrophil counts reaches at least 1,000/μl.

Neuromyelitis optica (NMO, Devic's disease) is an autoimmune, inflammatory, demyelinating central nervous system disorder in which a person's own immune system attacks the optic nerves and spinal cord and is characterized by concurrence of optic neuritis and transverse myelitis, typically associated with a lesion in the spinal cord extending over three or more vertebral segments. Although it is most commonly relapsing, it is distinct from multiple sclerosis in that it is more severe, tends to spare the brain, and is associated with a longitudinally extensive lesion on spinal cord MRI. Furthermore, NMO is associated with a highly specific serum autoantibody marker, NMO-IgG, which targets the water channel aquaporin-4. The disease follows a relapsing course in more than 90% of patients. At present, parenteral corticosteroids are widely employed as first-line treatment of optic neuritis and myelitis attacks, whereas therapeutic plasmapheresis is applied in the case of corticosteroids failure. Various strategies for the prevention of NMO relapses have been employed in small case series with modest activity. Immune based therapies, in order to be effective, need to be started early in the disease course while Devic's disease is predominantly an immune-mediated and inflammatory disease. Since 50% of patients with NMO are confined to a wheelchair within 5 years of onset, new therapies are needed in this disease. We now propose, as a phase I study, complete immune ablation and subsequent reconstitution with autologous stem cells.

Based on the experience of the pilot studies, the current protocol will mobilize stem cells with granulocyte-colony stimulating factor (G-CSF) and cyclophosphamide and collect stem cells by apheresis. A subsequent bone marrow harvest will be performed only if needed to supplement the peripheral blood stem cells (PBSC). Based on experience of autoimmune flares in patients receiving G-CSF alone for mobilization, patients will be mobilized with cyclophosphamide 2.0 g/m2 and G-CSF 5- 10 mcg /kg. In order to avoid cumulative cardiac toxicity from cyclophosphamide and to allow culture of HSC product, three weeks must separate the administration of cyclophosphamide for mobilization and for conditioning. Cyclophosphamide 50 mg/kg/day will be given IV over 2 hours in 500 cc of normal saline. If actual weight is < ideal weight, cyclophosphamide will be given based on actual weight. If actual weight is > ideal weight, cyclophosphamide will given as adjusted weight. Adjusted weight = ideal weight + 25% (actual weight minus ideal weight). Hydration-guidelines, NS at 150-200 ml/hr should be given 2 hours before cyclophosphamide and continued until 24 hours after the last cyclophosphamide dose. The rate of hydration will be aggressively adjusted. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status. r ATG 0.5 mg/kg given on day -5, then 1.0 mg/kg given on day -4, then 1.5 mg/kg given on days -3 through -1. r ATG is infused over 10 hours. Premedicate with Acetaminophen 650 mg po and Diphenhydramine 25 mg po/IV 30 minutes before the infusion.

Rituxan ( Rituximab ) - The dose of 500 mg of Rituximab will be diluted in 500 ml 0.9 % NS and infused per standard Rituximab infusion guidelines, given on days -6 and on day + 1. Following the guidelines, Rituximab will be started at 50 mg/hr. If no reaction occurs, the dose will be increased by 50 mg/hr every 30 minutes to a maximum of 400 mg/hr. G-CSF - guidelines, 5-10 mcg/kg/day will be started day + 5 and continued until the absolute neutrophil counts reaches at least 1,000/µl.