The primary objective is to cure multiple myeloma with less toxic allogeneic bone marrow transplantation while inducing renal allograft tolerance through mixed chimerism in patients with end stage renal failure and multiple myeloma

The induction of transplantation tolerance involves the specific elimination of the immune response to the transplant but not to other antigens. In the realm of kidney transplantation, tolerance means that the recipient is unable to detect the donor transplant kidney as foreign, and therefore the recipient is unable to reject the kidney. Donor bone marrow engraftment leads to kidney graft tolerance in animal models. Renal failure is a major complication of multiple myeloma, a plasma cell malignancy for which the only known cure is allogeneic bone marrow transplantation. Standard bone marrow transplantation is associated with frequent toxicity in patients with multiple myeloma, and is generally no considered an option for those patients with end stage renal disease. Myeloma patients are excluded from conventional renal transplantation protocols because of their underlying malignancy. A less toxic bone marrow transplantation protocol, combined with renal transplantation, could provide an opportunity for cure of the myeloma and correction of ESRD in patients with this disease. In addition, successful marrow engraftment may be expected to lead to a state of tolerance. Successful implementation of tolerance would be a major benefit to transplant recipients. The significance of developing tolerance is that the patient would be spared the disabling complications of indefinite immunosuppression, which include infections, cataracts, osteoporosis, diabetes, atherosclerosis, hypertension, and malignancy

Recipient Inclusion Criteria

1. Participants with end-stage renal failure due to or in association with greater than or equal to stage II multiple myeloma
2. Males or females 18 - 65 years of age.
3. Participants must have an HLA-matched or one of six HLA A, B, or DR antigen-mismatched related donor, with high resolution molecular DR allele determination.
4. Men and women of reproductive potential must agree to use a reliable method of birth control during the treatment, and women should do so for a period of 2 years following the transplant.
5. Participants should be on dialysis or have a CrCl <20 ml/min.
6. Participants must receive medical clearance by a cardiologist prior to conditioning for transplant.
7. Life expectancy greater than or equal to 6 months.
8. Recipient ability to understand and provide informed consent.

Recipient Exclusion Criteria:

1. Evidence of active infection as defined by: a) clinical syndrome consistent with viral or bacterial infection (e.g., influenza, URI, UTI) or b) fever with a clinical site of infection identified, or c) microbiologically documented infection, including, but not limited to, bacteremia or septicemia.
2. Participation in other investigational drug use at the time of enrollment.
3. Contraindication to therapy with any one of the proposed agents (e.g., history of allergy to horse serum in ATG).
4. Serologic positivity to HIV, HCV, or HbsAg positivity.
5. Women of childbearing age in whom adequate contraception cannot be maintained.
6. Malignancy within the past two years other than multiple myeloma, excluding basal cell carcinoma of the skin and carcinoma in situ of the cervix.
7. AST/ALT > 3 x normal or bilirubin > 1.5 x normal (unless due to Gilbert's syndrome).
8. Pregnancy or uncontrolled serious medical illness not related to underlying myeloma.
9. Cardiac ejection fraction < 40% by echocardiogram; individual assessment if ejection fraction between 40% and 50%.
10. FEV1 < 50% predicted or corrected DLCO < 50% predicted.
11. ABO blood group incompatibility in the host-vs-graft direction.

Donor Inclusion Criteria:

1. HLA-matched or one of six HLA A, B, or DR antigen-mismatched related male or female donor 18-65 years of age.
2. ECOG performance status 0 or 1.
3. Excellent health per conventional pre-donor history (medical and psychosocial evaluation).
4. Acceptable laboratory parameters (hematology in normal or near-normal range; liver function < 2 times the upper limit of normal and normal creatinine).
5. Compatible ABO blood group.
6. Negative donor lymphocyte crossmatch.
7. No positive testing for viral infection (HbsAg, HIV, HCV, HTLV-1).
8. Cardiac/Pulmonary evaluation within normal limits (CXR, EKG).
9. Donor ability to understand and provide informed consent.