Rheumatoid Arthritis:Tolerance Induction by Mixed Chimerism

Participant Inclusion Criteria: Age > 18 and < 60 years at time of pre-transplant evaluation. An established clinical diagnosis of rheumatoid arthritis by American College of Rheumatology criteria. Patients must have failed an autologous hematopoietic transplant or have failed to respond to either methotrexate or leflunomide in combination with a TNF inhibitor. Failure is defined as an inability to tolerate treatment with at least 6 swollen joints and 20 involved joints or inability to answer at least 70% of HAQ questions with "no difficulty" despite 2 or more months of treatment. Ability to give informed consent. Patient must have a HLA matched sibling donor at the A, B, C, and DR loci to proceed or HLA matched cord blood donor. If donor is HLA matched cord blood, cord blood stem cells will be obtained from the NMDP (1-800-548-1375) and one or two units of HLA matched cord blood will be infused on day zero. Participant Exclusion Criteria History of coronary artery disease, or documented congestive heart failure. HIV positive. Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemoradiotherapy. Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis. Positive pregnancy test, inability or unwillingness to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible. FEV1/FVC < 70% of predicted, DLCO < 40% of predicted. Resting LVEF < 45 %. Bilirubin > 2.0 mg/dl (unless due to Gilberts), transferase (AST) > 2.5 x upper limit of normal. Serum creatinine > 2.0 mg/dl. Donor Exclusion Criteria Age < 18 years. Positive for HIV-1, HIV-2, HTLV-I, HTLV-II. Active hepatitis B or C. History of a malignancy except for a localized cancer such as skin cancer that is deemed cured. History of myocardial infarction or congestive heart failure. Inability to give informed consent. Current pregnancy.