6 September 1999
New hope for transplant patients
by Kate Melville
One of the great success stories of the 20th century has been organ transplants.
Unfortunately these lifesaving procedures have a major downside, the need for organ recipients to take powerful drugs to suppress their immune system for the rest of their lives. Now doctors at Massachusetts General Hospital have deliberately induced a state of immune tolerance in a transplant recipient, enabling the patient to discontinue drug treatment without rejecting a transplanted organ (a kidney).
The patient, developed kidney failure as a result of a cancer of the bone marrow and received both a kidney and bone marrow transplant from her sister in 1998. The medical teams goal was to induce a state of mixed chimerism, in which both the donor and recipients immune systems are 'blended' to prevents rejection of the transplanted organ by the recipient's body and suppresses an attack of the donor's immune cells on the recipient's organs, a dangerous condition called graft-versus-host disease. In this specific case while the strategy aimed to treat both kidney failure and the underlying malignancy, the achievement is an important breakthrough for the thousands of patients who require organ transplants each year.
Dr. Benedict Cosimi, chief of the MGH Transplantation Unit said, "This is a first step toward the day when transplant recipients can be made tolerant to their donors' organs without the risks and costs of life-long immunosuppressive drugs. We hope to be able to use this approach with less-closely-matched donors, providing even more options for patients needing transplanted organs."
The MGH Transplantation Biology Research Center, in collaboration with BioTransplant, has been studying mixed chimerism and its possible applications for both inducing tolerance of organ transplants and fighting blood-cell cancers for several years. The patient in the trial was unusual as her myeloma caused her kidneys to fail, and she did very poorly on dialysis. Her cancer made her ineligible for a regular kidney transplant, and her kidney failure made her unable to tolerate the toxicity of standard bone marrow transplant preparation. After the double transplant from her sister, the patient had normal kidney function with no sign of graft-versus-host disease. She received the immunosuppressive drug cyclosporine after the transplant, but this was tapered off and discontinued 73 days after the procedures. Two post-transplant donor-white-blood-cell infusions were also given in an attempt to suppress her myeloma, which remains at a nearly undetectable level at this time.