Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases
Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases
This phase II trial studies the side effects and how well carmustine, etoposide, cytarabine
 and melphalan together with antithymocyte globulin before a peripheral blood stem cell
 transplant works in treating patients with autoimmune neurologic disease that did not respond
 to previous therapy. In autoimmune neurological diseases, the patient's own immune system
 'attacks' the nervous system which might include the brain/spinal cord and/or the peripheral
 nerves. Giving high-dose chemotherapy, including carmustine, etoposide, cytarabine,
 melphalan, and antithymocyte globulin, before a peripheral blood stem cell transplant weakens
 the immune system and may help stop the immune system from 'attacking' a patient's nervous
 system. When the patient's own (autologous) stem cells are infused into the patient they help
 the bone marrow make red blood cells, white blood cells, and platelets so the blood counts
 can improve.
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

 -  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 standard 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;
 patients who are unable to perform pulmonary function test (because of underlying
 disease) will be excluded if the oxygen saturation is < 92% on room air

 -  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