In an ITN study of combined kidney and bone marrow transplantation, four of five subjects studied were able to be removed from all anti-rejection medications and maintain functioning kidney transplants. The study was led by Drs. David Sachs and Ben Cosimi of Massachusetts General Hospital in Boston, and published in the January 24, 2008 issue of the New England Journal of Medicine.
The trial examined a technique known as mixed chimerism, which results in the transplant recipient's immune system being a mix of their own and their donor's. The process begins with the partial destruction of the transplant recipient's bone marrow using cytotoxic drugs often used for cancer treatment. Other agents then reduce the patient's supply of T cells, which are implicated in transplant rejection. Finally, the donor kidney, as well as some of the donor's bone marrow are transplanted simultaneously. Recipients must be confined in a sterile environment for a short time following the procedure to prevent infection while their immune system rebuilds.
Using this technique, Dr. Sachs and colleagues transplanted five patients with end-stage renal disease with bone marrow and kidney transplants from well matched (HLA single-haplotype mismatched) living related donors. In four of the recipients, it was possible to discontinue all immunosuppressive therapy within 9 to 14 months after the transplantation. In these individuals, kidney function has remained stable for between 2 and 5 years since transplantation. One subjects showed signs of humoral rejection and remains on immunosuppressive agents.
T cells from the four operationally tolerant recipients, when tested in vitro, showed donor-specific unresponsiveness and biopsy specimens showed high levels of FoxP3 mRNA, suggesting that regulatory T cells may play a role in the success of the procedure.