Carmustine, Etoposide, Cytarabine, Melphalan, and Antithymocyte Globulin Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Autoimmune Neurologic Disease That Did Not Respond to Previous Therapy

PRIMARY OBJECTIVES:

I. Evaluate the safety of high-dose carmustine, etoposide, Ara-c (cytarabine) and melphalan
(BEAM) and Thymoglobulin (antithymocyte globulin) as a high-dose immunosuppressive treatment
(HDIT) regimen in patients with severe, refractory neurological autoimmune disease.

SECONDARY OBJECTIVES:

I. Evaluate disease responses and the duration of response to HDIT and autologous
hematopoietic stem cell transplantation (HSCT).

II. Determine the efficacy and safety of G-CSF (filgrastim) and prednisone or
cyclophosphamide for hematopoietic stem mobilization in patients with neurological autoimmune
diseases.

OUTLINE:

Patients receive carmustine intravenously (IV) on day -6, etoposide IV and cytarabine IV
twice daily (BID) on days -5 to -2, melphalan IV on day -1, and antithymocyte globulin IV on
days -2 and -1. Patients then undergo autologous or syngeneic peripheral blood stem cell
transplant on day 0. Patients also receive prednisone orally (PO) once daily (QD) on days
7-21, followed by 2 week taper.

After completion of study treatment, patients are followed up at 3 months, 1 year, and then
annually thereafter for up to 5 years.

Inclusion Criteria:

- Patients with an autoimmune disorder of the central or peripheral nervous system will
be eligible; this will include:

- Primary Central Nervous System (CNS) vasculitis

- Rasmussen's encephalitis

- Autoimmune peripheral neuropathy (anti-Hu [Anna-1], anti-GM1 [GD1b], anti-MAG,
anti-ganglioside, anti-sulfatide)

- Autoimmune cerebellar degeneration

- Gait Ataxia with Late age Onset Polyneuropathy (GALOP)

- Stiff Person Syndrome

- Chronic Inflammatory Demyelinating Polyneuropathy

- Myasthenia Gravis

- Lambert-Eaton myasthenic syndrome

- Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) / tropical
spastic paraparesis (TSP)

- Opsoclonus / myoclonus (anti-Ri)

- Neuromyelitis optica

- Multiple sclerosis (only patients with relapsing/remitting multiple sclerosis
[MS] will be included)

- Other central or peripheral nervous system autoimmune diseases as approved by
study neurologists and the Fred Hutchinson Cancer Research Center (FHCRC) faculty
at Patient Care Conference (PCC)

- Patients must satisfy the criteria for a diagnosis of one of the severe neurological
autoimmune disorders outlined

- Evidence of disease activity as outlined (e.g. gadolinium enhancement on magnetic
resonance imaging of the brain or clinical progression)

- Patients must have failed at least 2 lines of stand therapy as outlined for the
specific diseases

- DONOR: Sibling of any patient enrolled on this protocol proven by ABO typing, human
leukocyte antigen (HLA) typing and variable number tandem repeat (VNTR) analysis to be
syngeneic with the patient (e.g. identical twin)

- DONOR: Willing to undergo multiple apheresis procedures (except donors < 12 years who
will undergo bone marrow harvests)

Exclusion Criteria:

- Pregnancy or expressed plans to become pregnant within 1 year of the procedure

- Patients who are serologically positive for human immunodeficiency virus (HIV)

- Patients with pulmonary, cardiac, hepatic or renal impairment that would limit their
ability to receive cytoreductive therapy and compromise their survival; this should
include patients with any of the following:

- Severe pulmonary dysfunction associated with a carbon monoxide diffusing capacity
(DLCO) (corrected for hemoglobin) < 60%, or requires supplemental oxygen

- Uncontrolled malignant arrhythmias, or clinical evidence of congestive heart
failure (New York class III-IV) or ejection fraction < 50%

- Renal disease with estimated glomerular filtration rate (GFR) by creatinine
clearance or iothalamate clearance < 50 ml/min/1.73 m^2 body surface area

- Serum glutamate pyruvate transaminase (SGPT)/aspartate aminotransferase (AST) > 3
times normal or direct bilirubin greater than 2.5 mg/dL on two repeated tests

- Active uncontrolled infection

- Demonstrated lack of compliance with prior medical care

- Patients whose life expectancy is limited by illness other than their neurological
condition

- Patients with evidence of myelodysplasia

- Active malignancy (excluding localized squamous cell or basal cell carcinoma of the
skin)

- DONOR: Inadequate documentation that donor and recipient are syngeneic

- DONOR: Donors who do not fulfill criteria as apheresis donors as established by
institutional guidelines

- DONOR: Concordant for autoimmune neurological disease(s) as determined by neurological
evaluation