Doctors aiming to prevent the potentially life-threatening complications following an organ transplant without the use of currently available drugs that may cause unwanted side effects was one focus at a meeting of transplantation specialists in Philadelphia in early April.
Eliminating Immune Suppression?
One study released at the meeting1 focused on a therapeutic approach known as "Mixed Chimerism". "Induction of mixed chimerism has the potential to overcome the current limitations of transplantation, namely chronic rejection, complications of immunosuppressive therapy, and the need for xenografts [a transplant from one species to another] …" wrote David Sachs, MD, and Megan Sykes, MD, of the Transplantation Biology Research Center at Massachusetts General Hospital in Boston, in a 2001 paper.2
In traditional organ transplantation, one of the most serious complications is the risk that the recipient's body will reject the new organ. While the risk of rejection slowly decreases over time, it never completely goes away. Thus, medications designed to suppress the recipient's immune system and thus reduce the chances of rejection, are given for years after the procedure—often indefinitely. These medications include induction immunosuppression, designed to prevent acute rejection immediately after the transplant; anti-rejection immunosuppression, designed to treat an acute rejection episode immediately after or up to 30 days after a transplant procedure; and maintenance immunosuppression, aimed at long-term immunosuppression.3
The 'Most Advanced' Approach Available
Mixed chimerism is an approach aimed at reducing or completely eliminating the need to prescribe potentially toxic immunosuppressive medications for transplant patients. Using this technique, a donor's bone marrow is transplanted to the recipient along with the transplanted organ. In this way, the recipient's immune system recognizes the new organ and the odds of rejection are lowered.4
"It's the most advanced protocol out there," explained Joren Madsen, MD, head of the Cardiothoracic Transplantation Laboratory at Massachusetts General Hospital. "Drugs are risky. They suppress the immune system, but they also block the body's resistance to infections, cancers and other attackers, putting patients at even higher risk of illness or death."
The approach precludes a patient's need to use follow-up immunosuppressive therapies for years after their operation, experts contend. "Those immunosuppressive drugs are the major causes of mortality and morbidity after transplantation," Madsen said, in an e-mail interview.
Evidence in the Medical Literature
Currently, it's been shown that mixed chimerism works in kidney transplants between immunologically identical donors and recipients. But it still needs to be tested in transplants of other organs and between non-identical donors and recipients, Madsen explained. One such trial involving two patients who underwent kidney transplants was published three years ago.5 He says a group of physicians at Massachusetts General Hospital, including Drs. Sachs and Sykes and Ben Cosimi, MD, is continuing studies on the protocol.
In the Meantime
But while other experts concur about the promising impact of mixed chimerism, until it moves beyond the experimental stage, they say there's a need for safer, less toxic, anti-rejection medications that transplant patients can take.
Chris Larsen, MD, a transplant surgeon and immunologist at Emory University in Atlanta, says there's a need to develop new drugs that target the immune system after transplantation without presenting unwanted side effects. Some of the current medications taken today affect not only the immune system, but other parts of the body that cause side effects requiring additional medicines.
"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," Larsen explained, in a statement. "We want patients to take fewer, not more, pills."
One of the leading candidates in this area is known as co-stimulation blockers, Larsen points out, which are designed to target the immune system while sparing other organs and unrelated physiological functions, thus avoiding many negative side effects.
Related Medical Research
A second study released at the transplant meeting last week and earlier published in 20046 showed how infants under age 1 year can tolerate heart transplants from donors of different blood groups without the risk of organ rejection. That's because their bodies don't yet harbor antibodies that would normally attack these "foreign" organs from a donor of a different blood type.
"The baby's body educates itself to accept the organ and became tolerant of the blood type," explained Lori West, MD, a pediatric cardiologist at the Hospital for Sick Children in Toronto, and a study co-investigator.
According to Larsen, T-cell response—how the body's immune system identifies and responds to foreign or native antibodies—is a key focus of transplant research today. He says knowledge gained in his kidney transplant research is becoming useful to experts who conduct studies on heart and lung transplantation. "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," he added.
1. International Society for Heart and Lung Transplantation (ISHLT) 25th Anniversary Meeting and Scientific Sessions. 2005 Apr 5-9. Philadelphia, PA.
2. Sykes M, Sachs DH. Mixed chimerism. Philos Trans R Soc Lond B Biol Sci 2001 May 29;356(1409):707-26.
3. United Network for Organ Sharing. Medications: Protecting Your Transplant. Available at: http://www.transplantliving.org/afterthetransplant
/typesOfSuppressants.aspx. Accessed April 13, 2005.
4. Institute for Cellular Therapeutics. University of Louisville. Available at: http://ict.louisville.edu/bedside/bmt.html. Accessed April 13, 2005.
5. Buhler LH, Spitzer TR, Sykes M et al. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. Transplantation 2002 Nov 27;74(10):1405-9.
6. Fan X, Ang A, Pollock-Barziv SM et al. Donor-specific B-cell tolerance after ABO-incompatible infant heart catheterization. Nat Med 2004 Nov;10(11):1227-33. [Epub 2004 Oct 24.]
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
