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Organ Tolerance for Transplant Patients Focus of Research Presented at ISHLT

Posted on: Friday, 8 April 2005, 09:00 CDT

ADDISON, Texas, April 8 /PRNewswire/ -- The human body's tolerance of a donor organ has traditionally been one of the greatest challenges of transplant medicine. Despite advances in transplant technology, tolerance and addressing complications, such as infection, from the use of immunosuppression drug therapy remain the leading causes of death in the initial years following an organ transplant.

Research focused on patients' tolerance of a donor organ, exploring bone marrow transplants, drug therapies which target the immune system and infant survival, will be presented on Saturday at the International Society for Heart and Lung Transplantation (ISHLT) Annual Meeting and Scientific Session in Philadelphia.

Total organ acceptance on the horizon

The future of donor organ tolerance is complete acceptance of the donor organ, without additional therapies to ensure acceptance.

A "Mixed Chimerism" protocol, involving a bone marrow transplant along with the organ -- all from the same donor -- is successful in inducing tolerance. It is so effective that patients can live without the years of follow-up therapies that have been the hallmark of post-transplant patient care.

"It's the most advanced protocol out there," says Dr. Joren Madsen, Massachusetts General Hospital. Madsen, who will participate in the session, "The Future of Tolerance," says that the trials have produced "impressive results" in humans.

The protocol study, conducted by Drs. David Sachs and Megan Sykes, also of Massachusetts General Hospital, would mean an end to years of drug therapy to assure patient acceptance of the donor organ.

"Drugs are risky," he says. "They suppress the immune system, but they also block the body's resistance to infections, cancers and other attackers, putting patients at an even higher risk of illness or death."

Drugs that target the immune system

Chris Larsen, M.D., a kidney transplant surgeon and immunologist at Emory University in Atlanta, agrees with Madsen's assessment, but believes that while waiting for the Mixed Chimerism protocol to be put into widespread practice, the right combination of newer, safer drugs may be a beneficial alternative to patients. Drugs currently used to suppress the immune system and prevent the body's rejection of the donor organ do not exclusively target the immune system. Some of the current medications transplant patients take today affect other areas of the body and cause side effects that require additional drugs to address these side effects, says Larsen.

"We want to change that by developing a more effective combination of new drugs that target the immune system without side effects such as kidney toxicity, high blood pressure, high cholesterol and Diabetes. We want patients to take fewer, not more, pills." Larsen points to an emerging class of drugs -- Costimulation blockers -- that target the immune system while sparing other organs and unrelated functions, thus avoiding many of the side effects.

Factors like T-cell response -- how the immune system identifies and responds to foreign or native antibodies -- are of interest to the transplant community, and researchers have identified specific immune system pathways on which to focus their attention.

Larsen says the knowledge gained in his kidney transplant research is useful to those in the heart and lung transplant community. "There are commonalities in our respective disciplines -- we're all working toward long- term survival and quality of life -- we should share what we know with each other," says Larsen, who is scheduled to present, "Toward Clinical Tolerance" tomorrow at the ISHLT Meeting.

Infant transplant patients have better survival odds

According to a study published in Nature Medicine, infants under one year of age can tolerate heart transplants from donors of different blood groups without the risk of organ rejection, because unlike older children and adults, infants do not yet have the antibodies that would normally reject antigens from a different blood type.

"The baby's body educates itself to accept the organ and become tolerant of the blood type," says Dr. Lori West, a pediatric cardiologist at the Hospital for Sick Children in Toronto and co-author of the study. West will present her findings tomorrow in a lecture, "Clinical Neonatal Tolerance" at the ISHLT Meeting.

The tolerance of the donor organ has far-reaching results. Many babies who undergo heart transplantation require a second donor heart at some point. The results of the study show that because the immune cells that would normally respond and attack the donor organ were eliminated with the first transplant, the patient can again receive a donor heart from that same blood type.

The Toronto Protocol, as the study is known, has now been adopted at 15 medical centers around the world, with similar successes at each of the centers. "This knowledge will save lives," says West. "More babies will survive congenital heart defects and go on to live fulfilling lives with a donor heart. We can use this knowledge to decrease the amount of time a patient must wait for a new heart -- we'll be able to use donor organs more efficiently and perform increasingly successful transplants."

About ISHLT

The International Society for Heart and Lung Transplantation (ISHLT) is a not-for-profit organization dedicated to the advancement of the science and treatment of end-stage heart and lung diseases. Created in 1981, the Society now includes more than 2,200 members from 45-plus countries, representing a variety of disciplines involved in the management and treatment of end-stage heart and lung disease.

ISHLT maintains two vital databases. The International Heart and Lung Transplant Registry is a one-of-a-kind registry that has been collecting data since 1983 from 223 hospitals from 18 countries. The ISHLT Mechanical Circulatory Device (MCSD) database has been collecting data since 2002 with the aim of identifying patient populations who may benefit from MCSD implantation; generating predictive models for outcomes; and assessing the mechanical and biological reliability of current and future devices. For more information, visit http://www.ishlt.org/ .

International Society for Heart and Lung Transplantation

CONTACT: Lauren Mason, +1-210-857-2521, or lmason@masonpr.com , forInternational Society for Heart and Lung Transplantation

Web site: http://www.ishlt.org/

Source: PRNewswire

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