Combined Bone Marrow and Renal Transplantation for Hematologic Disorders With End Stage Renal Disease
Condition: Multiple Myeloma; Amyloidosis
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Kidney Failure, Chronic; Hematologic Diseases; Amyloidosis
Study type: Interventional

Summary: 
      This pilot trial offers the unique opportunity for both the treatment of multiple myeloma or
      systemic AL amyloidosis for which hematopoietic stem cell transplantation would be ordinarily
      indicated and the reversal of end-stage renal failure, while avoiding the risks associated
      with long-term standard anti-rejection therapy used in renal transplantation. The primary
      objectives of this study are to assess renal allograft tolerance (that is, the acceptance of
      the kidney without the need for anti-rejection therapy), assess anti-tumor response rates in
      multiple myeloma and AL amyloidosis, and assess complication rates for genetically (HLA)
      matched related donor combined bone marrow and kidney transplantation using a low dose total
      body irradiation based preparative regimen.
    

Detailed description: 
      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 and AL amyloidosis for which the only known cure is
      allogeneic bone marrow transplantation. Standard bone marrow transplantation is associated
      with prohibitive toxicities in patients with end stage renal disease, and is generally not
      considered an option for those patients. Patients with multiple myeloma and AL amyloidosis
      are excluded from conventional renal transplantation protocols because of their underlying
      malignancy. A less toxic bone marrow transplantation protocol, utilizing low dose total body
      irradiation and anti-thymocyte globulin, combined with renal transplantation, could provide
      an opportunity for cure of the myeloma or amyloidosis and correction of end stage renal
      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 could be spared the
      disabling complications of indefinite immunosuppression, which include infections, cataracts,
      osteoporosis, diabetes, atherosclerosis, hypertension, and malignancy.
    

Intervention name(s): Tacrolimus; Equine Anti-thymocyte globulin; Kidney transplant from a related donor; Bone marrow transplant from a related donor; Total body irradiation 400 centigray (200 cGy X 2)
Intervention type(s): Drug; Drug; Procedure; Drug; Radiation
Intervention description(s): Tacrolimus starting on Day -1; 20 mg/kg IV on Days -3, -1, +1, +3; On Day 0 the renal transplant is performed according to standard surgical techniques.; Donor bone marrow (> 2 x 10e8 nucleated cells/kg of recipient body weight) is prepared for infusion according to the standard procedure. The infusion begins in the operating room as soon as the vascular anastomosis of the renal allograft has been completed.; On transplant day -1
Intervention MeSH terms: Tacrolimus; Antilymphocyte Serum
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HLA matched; bone marrow transplantation; kidney transplantation