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.