Forget organ allocation controversies, reports of new immunosuppressive drugs, the donor shortage, voluntary organ and tissue donation, and skepticism about limb transplants. That was the 1990s.
Graft tolerance without immunosuppression, injecting porcine islet cells to treatment of diabetes, transplanting HIV patients, hand transplants without fear of problems caused by immunosuppression, and worldwide commerce in organs. (reported in the last issue of Transplant News.)
The XIX Congress of the Transplantation Society proved to be a fertile launching pad for a variety of new approaches being studied to address the ongoing issues surrounding rejection, the donor shortage, recipient selection, and experimental new procedures/methods for treating patients with a variety of transplant/implant needs.
The long-term importance of the findings will be debated in the coming months. However, the availability of the information made available by the Society's first-class press operation assured that transplant professionals and the general public are aware of the claims and advances.
Here's an overview of some of the main stories that came out of the meeting.
Graft tolerance without immunosuppression-how close is it? Three studies presented at the Congress suggested that researchers are moving closer to the "Holy Grail" of transplantation - finding a way to coax the human body into accepting a transplanted organ without having to use powerful immunosuppressive drugs.
All 3 studies reported achieving some short-term success in weaning transplant recipients off of drugs but none laid claim to having found the answer. Each involved infusing the transplant recipient with bone marrow or tissue from the donor followed by weaning them off of the immunosuppressive drug regimen over time.
Kareem Abu-Elmagd, MD, associate professor of surgery at the University of Pittsburgh Thomas E. Starzl Transplantation Institute, presented data on 22 small intestine, liver-small bowel and multivisceral transplant recipients who received donor bone marrow and intestinal grafts. The grafts were irradiated prior to beginning lower-than-usual doses of just one immunosuppressive drug beginning the day after receiving the transplant.
Abu-Elmagd said 12 of the 22 patients, who had no rejection for up to 90 days, were selected for weaning off tacrolimus. The process was conducted in a step-wise fashion, with the reductions in the number of doses made every 2 weeks. All the patients had their doses reduced to once or twice a week. The protocol calls for the patients to follow their reduced regimen for up to a year before complete withdrawal will be considered.
At a congress press briefing Thomas Starzl, MD, said similar success rates using the same protocol with kidney and liver recipients had been achieved. "What we're looking at here is drastic reduction of immunosuppression, and that, of course, is a necessary step if you're going to get real tolerance," Starzl said.
H.L.Trivedi, MD, of the Institute of Transplantation Sciences in Gujarat, India, reported on a study involving 43 patients who received living donor kidneys following the infusion of donor stem cells into the recipients blood, marrow, liver and thymus. Trivedi said that within 1 year 32 had been weaned off of cyclosporine and remain rejection free. The patients continue to be treated with on low doses of less powerful drugs, however.
Samuel Strober, MD, professor of immunology and rheumatology at the Stanford University School of Medicine, reported on 4 patients who received stem cells and a kidney from the same donor. Following the transplant, the recipients received 10 radiation cycles and were infused with the stem cells.
Strober said 2 of the patients were weaned off all immunosuppressive drugs after 1 year, while a 3rd is ready to be weaned. Because of an early rejection episode the 4th recipient was unable to be weaned. However, the patients who stopped taking all drugs developed graft rejection symptoms after 5 months and put on low-dose anti-rejection drugs.
Alan Kirk, MD, a researcher at the National Institutes of Health (NIH), said the new studies should be taken with caution. "None of these protocols are ready for prime time," he said.
Kirk's research on tolerance gained national attention in 1997 when he and colleagues reported on an experimental therapy using special proteins with monkeys which was widely perceived as a major step in the quest to achieve tolerance.
Kirk, who was a Lieutenant Commander in the Navy, and Captain David Harlan of the Naval Medical Research Institute in Bethesda, MD, reported that a 4-week series of injections of two types of proteins, tested in monkeys, appeared to teach the immune system not to reject the transplanted organs. (Transplant News, August 11, 1997) The results were reported in the August 5th issue of the Proceedings of the National Academy of Science.
Pig cells a "cure" for diabetes? Perhaps the most controversial data released at the congress was presented by Dr. Rafael Valdes, of the Hospital Infantil de Mexico, who reported successfully transplanting insulin-producing pig cells into 6 children with type 1 diabetes. Valdes said 1 child remained insulin-free after 1 year and the other 5 had their insulin requirements reduced by 50%. The trial consisted of 12 Mexican teenagers age 11 to 17. The 6 other children in the trial experienced no benefit from the pig cells. The children's transplants were performed without the use of immunosuppressive drugs.
Valdes reported that after 1-year 6 of the 12 children have functioning transplants, and the remainder are receiving insulin doses of 50% to 80% of what they were receiving before the islet transplants. All have stable blood sugar.
David White, MD, the co-investigator of the study and professor of xenotransplantion at the Robarts Research Institute at the University of Western Ontario in London, enthusiastically supported Valdez findings.
"It suggest that Sertoli cells can prevent rejection across the species barrier. It's the first evidence we have in humans," White said, in an interview with the Toronto Star.
Reacting to charges that it may have been unethical to conduct the transplants on teenagers, White said at a congress press briefing that the trials were safe. "The data has been submitted and will be published soon," he said. "One of the attractions of this research was its incredible safety, it was very safe and simple."
Camillo Ricordi, MD, scientific director of the University of Miami's Diabetes Research Institute and co-chair of the congress, called Valdes findings "the most remarkable development ever following an islet cell transplant experiment," if the new findings stand the test of time. "This is either a Nobel Prize-class development" and I wish you luck in this direction-or it is not," Ricordi said at a press briefing.
David Cooper, MD, professor of surgery at the Harvard Medical School of Medicine, said he would like Valdes to seek FDA approval to conduct similar trials in the US. "If he did that, everyone would be happy," Cooper said.
Transplanting HIV patients-the time has come Several studies demonstrated that transplanting patients with well-controlled HIV virus should be considered for liver or kidney transplants. Researchers from the US and France, which collectively reported on 34 kidney and 17 liver transplants on HIV-positive patients, reported that after more than 1-year of follow-up, outcomes in patients are very similar to outcomes in non-HIV patients, and more importantly, the immunsuppressive drug regimens seem to have little effect on the progression of the HIV.
Peter Stock, MD, of the University of California, San Francisco (UCSF) reported they have performed 4 liver and 10 kidney transplants in HIV-positive patients. Stock, an associate professor of surgery at UCSF, said the success of anti-retroviral therapy (HAART) has allowed HIV-patients to be reevaluated as candidates for a transplant. He said that 13 of the 14 patients are alive with the 1 death attributed to a 15-year-old who underwent a liver transplant for hepatitis C who died as a result of a rapid recurrence of the hepatitis.
Stock said viral loads remained undetectable in all patients on HAART and patients on protease inhibitors required 25% of the dose of cyclosporine compared to patients on non-nucleoside reverse transcriptase inhibitors.
In Philadelphia, Anil Kumar, MD, of Hahnemann University, reported that 17 of 20 kidney recipients with HIV were still alive. None of the 3 deaths was due to the virus. Three of the patients received living donor organs, and 17 cadaver kidneys.
Dr. Didier Samuel of Paul Brousse Hospital in Villejuif, France, reported that 6 patients with both HIV and hepatitis C received liver transplants and 5 remained alive after 1-year. The researchers said transplanting patients with HIV and hepatitis C is feasible but cautioned it requires careful monitoring for hepatitis re-infection, drug interactions and of anti-retroviral toxicity.
Dr. Ashok Jain, of the University of Pittsburgh Thomas E. Starzl Transplantation Institute, reported that 2 of 7 liver transplant recipients with HIV virus died and all 4 kidney recipients are alive, several months to 5-years after transplantation. Hand transplants-immunosuppression worries seem unfounded
In an overview of 12 single hand and 4 double hand transplants performed since 1998, researchers from Italy, France and the US reported that rejection can be controlled effectively with the same mainstream immunosuppressive drugs used in solid organ transplants without serious complications.
Carla Granger, of the University of Louisville, reported that one of her patients had returned to work hanging gutters just 2 months after his single-hand transplant.
Dr. Jean-Michel Dubernard of the Hopital Edouard Herriot in Lyon, France, said the world's first double-hand transplant transplant patient is able to shave and take care of other personal hygiene tasks he was unable to do before the transplant.
Dr. Bruno Gridelli of the Riuniti di Bergamo Hospital in Bergamo, Italy, reported that 22 years after one patient's hand was severed, a hand transplant has afford the recipient the same sense of touch in his transplanted hand as his normal hand.
All of the transplant teams argued that hand transplantation and other types of composite tissue transplantation would benefit patients whose limbs have been severed or amputated or who require reconstructive surgery due to tumor resections or congenital deformities.
Spain leads world in per capita organ donation Spain continues to lead the world in per capita organ donation. Data released at the congress showed Spain's per capita donor rate was 32.5 people per million population ins 2001. They were followed by Austria - 23.0, Belgium - 21.6, and the US with 21.4. Experts estimate there are about 65,000 organs transplanted worldwide annually between 150,000 and 200,000 patients waiting for an organ.
(Editor's Note: The Transplantation Society's press operation was the best I've seen in the 12 year's of covering large transplant meetings. The formula of bringing the meeting to the press through a series of daily press briefings, copious copies of press releases and press availabilities, and the knowledge and professionalism of the press room personnel was first rate. Lisa Rossi, on loan from the University of Pittsburgh Medical School's press office, and the volunteers from the University of Miami deserve great credit for the success. The American Transplant Congress would be doing the transplant community a great service by adopting a similar approach at its next meeting.)
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|Comment:||Forget organ allocation controversies, reports of new immunosuppressive drugs, the donor shortage, voluntary organ and tissue donation, and skepticism about limb transplants. That was the 1990s.|
|Date:||Sep 27, 2002|
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