Combined Bone Marrow and Renal Transplantation for Hematologic Disorders With End Stage Renal Disease

Participant Inclusion Criteria

• Participants with end-stage renal failure due to or in association with multiple myeloma or systemic AL amyloidosis which hematopoietic cell transplantation is appropriate and a ≥ 50% five-year survival probability with transplantation is expected. This includes, but is not limited to:
• Multiple myeloma (MM), ISS stage II or III in complete or very good partial remission
• AL amyloidosis without significant cardiac disease
• Males or females 18 - 65 years of age.
• Participants must have an HLA-matched or one of six HLA A, B, or DR antigen-mismatched related donor, with high resolution molecular class I and II allele typing.
• 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.
• Participants should be on dialysis or have a CrCl <20 ml/min.
• Patients should not have evidence of renal recovery of their renal failure over a 90 day period of therapy for their underlying malignancy or other blood disorder.
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• Patients with a history of other malignancies excluding basal cell carcinoma of the skin and carcinoma in situ of the cervix with a disease-free survival interval of >2 years. Patients with the following malignancies must demonstrate a 5 year disease-free survival:
• Breast cancer with positive nodes
• Malignant melanoma (other than in situ)
• Colorectal cancer (other than Dukes Stage A or B1)
• Patients with multiple myeloma must have received previous treatment with a bortezomib-based regimen.

Patients with AL amyloidosis must have received previous treatment with a bortezomib-based regimen and/or autologous stem cell transplantation

• Patients with a history of malignant melanoma must be reviewed by an independent oncologist prior to enrollment.
• Recipient ability to understand and provide informed consent.

Participant Exclusion Criteria

• 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.
• Participation in other investigational drug use at the time of enrollment.
• Contraindication to therapy with any one of the proposed agents (e.g., history of allergy to horse serum in ATG).
• Serologic positivity to HIV or HCV.
• Women of childbearing age in whom adequate contraception cannot be maintained.
• AST/ALT > 3 x normal or bilirubin > 1.5 x normal (unless due to Gilbert's syndrome).
• Pregnancy or uncontrolled serious medical illness not related to underlying myeloma.
• Cardiac ejection fraction < 40% by echocardiogram.
• FEV1 < 50% predicted or corrected DLCO < 50% predicted.
• ABO blood group incompatibility in the host-vs-graft direction.
• Diagnosis of myelodysplastic syndrome

Donor Inclusion Criteria

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