Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
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.