Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure
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
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Remission status of multiple myeloma
Thomas R Spitzer, MD
Massachusetts General Hospital
United States: Institutional Review Board
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|