SAN FRANCISCO, April 24, 1999 -- Organ rejection occurs less often and is less severe in heart and lung transplant patients who receive infusions of bone marrow from the same donor, researchers from the University of Pittsburgh Medical Center (UPMC) reported today at the International Society for Heart and Lung Transplantation Annual Meeting.
"These results are particularly significant because hearts and lungs are usually more prone to rejection than other organs. Their cell composition contains fewer donor immune system cells that serve as natural defenses against an attack by the recipient’s immune system; donor bone marrow seems to enhance the immune capabilities and reduce the likelihood of rejection," explained Kenneth McCurry, M.D., assistant professor of surgery, division of cardiothoracic surgery, at UPMC.
Controlling rejection is the key to successful organ transplantation. For the most part, surgeons rely on drugs that suppress the patient’s immune response as their main line of defense against an immune system attack. But despite newer and better drugs, organ rejection can still occur, even years after transplantation.
The study included 31 heart and 26 lung transplant patients who received donor bone marrow within 72 hours of their transplant operations. The results were compared to 24 heart and 26 lung recipients who received organ transplants without bone marrow.
By giving donor bone marrow, the researchers’ aim was to enhance the cellular environment called chimerism, defined as the coexistence of recipient and donor immune cells. Having already proved that chimerism is present in long-term survivors of kidney and liver organ transplants, some of whom have been weaned from a life-long regimen of immunosupressant drugs, researchers wanted to promote, even hasten this biological process with bone marrow.
In heart transplant patients, acute cellular rejection in the first six months occurred in 38 percent of those who received bone marrow, compared to 82 percent of those who did not. Most of the rejection episodes in the group of bone marrow-augmented patients were mild as compared to moderate to severe in the recipients who did not receive bone marrow. There were no differences in the incidence of chronic rejection for the two groups of heart recipients.
In lung transplant patients, the most significant result was a reduced incidence of chronic rejection, a process that prevents air to pass through the lung’s bronchioles. Chronic rejection occurred in 9 percent of the bone marrow patients and in 42 percent of those who did not receive bone marrow. In addition, those lung patients receiving bone marrow had higher measures of donor-specific hyporeactivity. This indicates that the recipient’s immune defense is capable of fighting unwanted infections but is less likely to initiate an attack against the donor organ.
In studies to detect chimerism in a small subset of patients a year after transplantation, levels appeared to be higher in those who received bone marrow. The safety of the bone marrow procedure was also a parameter studied. Patients were not pre-treated with irradiation to "make space" for the bone marrow, nor was the bone marrow modified in any way. As a result, the researchers believe the risk of graft vs. host disease (GVHD) was minimized. GVHD, a common complication of bone marrow transplantation, occurs when donor immune cells attack recipient tissues.
"The results in these patients who received the extra boost of donor immune system cells indicate the procedure is safe and augments the cellular environment we believe is necessary for long-term acceptance of a transplanted organ. Chimerism is a prerequisite for but not synonymous with tolerance," Dr. McCurry reported.
The study of combined solid organ and bone marrow transplants is the clinical centerpiece of a large research effort at UPMC. To date, more than 229 recipients of hearts, lungs, liver, kidney, pancreas, pancreatic islet cells and intestines have received bone marrow.
Chimerism became a major focus of study when in 1992, Thomas E. Starzl, M.D., Ph.D., professor of surgery at UPMC, brought to Pittsburgh 25 long-surviving recipients of kidney and liver transplants. Biopsies taken from the transplanted organs, lymph nodes, skin and other tissues revealed that donor leukocytes, or white blood cells, had migrated from the transplanted organs to recipient tissues, where they persisted years—in one case, for 29 years—after transplantation. Researchers also found recipient cells continuing to coexist with donor cells within transplanted organs. Such an observation provided confirmation that in organ transplantation, surgeons are not only replacing organ function but they are also exposing the recipient to the donor’s immune system.
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