March 8, 2012
New Hope For Organ Transplant Recipients
Organ transplant patients usually spend a lifetime on expensive and often dangerous anti-rejection drugs. But experts have announced that such drugs may not even be needed in the future, thanks to a new study that suggests patients receiving an organ that is less than a perfect match can be protected against rejection by a second transplant of the donor´s imperfectly matched stem cells. The study is being hailed as a game-changer for transplantation.
Experts announced the success of kidney transplants for a small number of patients, using a relatively new technique known as normothermic perfusion. This involves the warming of the kidney with oxygenated blood after it has been in cold storage. This technique also boosts the function of damaged kidneys from “marginal donors,” such as the elderly or those with high blood pressure and diabetes, and also reduces the risk of the organ being rejected.
Also, an injection of stem cells given with the kidney transplant could remove the need for patients to take anti-rejection drugs the rest of their lives to suppress the immune system. Preliminary tests of the technique were successful in a small number of patients.
The researchers, publishing their study in the journal Science Translational Medicine, said the research could have a “major impact” on transplant science.
The key issue with transplantation is the immune system´s recognition that the new organ is a foreign invader and bombards it. To prevent this from occurring, patients take powerful drugs to suppress their immune systems, and must do this for life. However, the drugs can have dangerous side effects, and in some instances, are ineffective, causing even more danger to the patient.
The study, carried out at the University of Louisville and the Northwestern Memorial Hospital in Chicago, involved eight patients.
Transplants came from a live donor, who also underwent a procedure to draw stem cells from the blood. The transplant recipient´s body was prepared using radiotherapy and chemotherapy to suppress their own immune system. The transplant was then performed, with the stem cells injected a few days afterwards. The idea is that the stem cells will help generate a modified immune system that no longer attacks the organ or its new owner.
The patients were still given anti-rejection drugs after the transplant. However, the aim was to reduce doses slowly, hopefully withdrawing them altogether over time. Five of the eight patients were able to do this within a year.
One of those is 47-year-old Lindsay Porter, from Chicago.
“I hear about the challenges recipients have to face with their medications and it is significant,” she said in a press statement. “It´s almost surreal when I think about it because I feel so healthy and normal.”
Another study patient, 56-year-old Deborah Bakewell, was on dialysis for nine hours a night, seven nights per week, for nearly two years after suffering kidney failure. She underwent normothermic perfusion in December 2010. Her kidney was rejected by six transplant centers, owing to the fact it was damaged, but the research team had faith their new technique could improve its chances of functioning.
Experts believe normothermic perfusion could increase the success rate of kidney transplants and extend the life of organs, while boosting the number of organs available from marginal donors by about 500 per year.
“My kidney function was about 8 percent and my organs were not filtering waste properly. I was getting more and more tired and kept getting kidney infections. Sometimes I thought I had terrible backache but it was actually a kidney infection,” Bakewell is quoted as saying by The Press Association, and reprinted by The Guardian.
Bakewell received her new kidney but her two own damaged kidneys were left in place.
“I feel fantastic now and my kidney function is just amazing. It´s probably quite a lot better than a lot of people my age with two kidneys. When I was on dialysis it was for nine hours a night, seven nights a week. Now I have my freedom. We have booked our first holiday in years for June, to Majorca,” an excited Bakewell said.
“The preliminary results from this ongoing study are exciting and may have a major impact on organ transplantation in the future,” said Joseph Leventhal, associate professor of surgery at Northwestern University Feinberg School of Medicine. He added that this technique may also improve the lives of people who receive other transplants.
While stem cells from organ donors have been used before, this is the first time it has been used for “mismatched” transplants, in which donors and recipients do not have to be related and immunologically similar.
If normothermic perfusion proves successful in a larger group of people, future transplant recipients may need to take anti-rejection drugs only briefly, and some who rely on them now could discontinue them safely.
The technique could also offer hope for patients receiving bone marrow transplants to treat blood cancers, speeding the process of finding a donor by allowing physicians to use stem cells that would normally be rejected as incompatible.
“Few transplant developments in the past half century have been more enticing,” transplant surgeons James F. Markmann and Tatsuo Kawai of Massachusetts General Hospital wrote in a commentary accompanying the study. These findings “may potentially have an enormous, paradigm-shifting impact on solid-organ transplantation.”
Markmann told BBC News that the greatest benefit of techniques described in the research would be to greatly improve the lives of transplant patients by freeing them of a lifetime of anti-rejection drug use. But it might also ease the shortage of transplantable organs somewhat by reducing the number lost to rejection, he said.
The National Kidney Foundation states 4,573 US patients died in 2008 awaiting a kidney transplant because of a donor shortage.
Markmann said the study offers a “huge potential” for donors who could donate stem cell transplants to patients fighting blood cancers. Currently, many of the 6,000 patients yearly who have a stem cell transplant “have to look far and wide for a perfect match.”
In a controversial move to protect the commercial interest in the new technique, the authors of the study declined to detail what stem cells were used and how they are identified and treated. But they reported that earlier studies in mice revealed that these facilitating cells “potently prevent graft-versus-host disease.”
Transplant patients were sent home with strict instructions to avoid exposure to sick people and germs and to wash their hands carefully for several days until their immune system stirred to life.
At one month after the transplants, three of the eight patients failed to achieve the state that would allow ongoing acceptance of the mismatched kidney. One eventually rejected the kidney and got another; the other two have staved off rejection with continued use of anti-rejection drugs. The remaining five were able to stop all drug use after a year without incident.
“We´re really excited about it,” Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville in Kentucky, and lead researcher of the study, told The Los Angeles Times.
She said she hoped next to use the new techniques to explore the transplantation of livers and pancreatic islet cells between mismatched donors and recipients.
The success of the new research´s five transplant patients has implications beyond the 93,000 Americans currently awaiting a kidney transplant. For some of the 12,000 patients awaiting hearts, lungs and other organs, the regimen could point the way to improving success rates and reducing reliance on anti-rejection drugs for them as well, said Ildstad.
The authors believe their research could also allow for the retroactive treatment of transplant patients who are living with imperfectly matched organs if those donors are still alive and willing to donate stem cells.
On the Net:
- Science Translational Medicine
- University of Louisville
- Northwestern Memorial Hospital, Chicago
- Northwestern University Feinberg School of Medicine
- National Kidney Foundation