Performing human-organ transplants without the necessity for a lifetime regimen of immunosuppressive drugs has been an enduring goal for transplantation medicine. Now, a new Medicare-approved protocol being implemented at UCLA Health with select living-donor kidney-transplant patients is bringing that dream closer to reality. “It is the Holy Grail,” says renal-transplant surgeon Jeffrey Veale, MD, who has led UCLA’s effort to develop the protocol. Dr. Veale was at a medical conference in 2009 when he heard the celebrated immunologist David H. Sachs, MD, talk about how Massachusetts General Hospital was creating immune tolerance in organ-transplant recipients, eliminating the need for lifelong anti-rejection drugs. “I was mesmerized,” Dr. Veale recalls. “Transplants with no immune suppression? I thought, ‘That’s incredible!’”
A lot has happened in the 12 years since that day in Jackson Hole, Wyoming, and today, UCLA Health is the only medical center in the U.S. practicing the tolerance protocol between well-matched siblings. The procedure has been performed at UCLA in two well-matched sibling pairs to date, with both kidney recipients successfully weaning off immunosuppression medication. In November, UCLA received approval from Medicare to provide the procedure.
While solid-organ transplants have been performed regularly since the 1950s, they always have required powerful drugs to prevent the recipient from rejecting the new organ. This is both expensive and risky for the recipient; these powerful immunosuppression drugs can have serious complications that include increased risk of cancer, infection, diabetes, hypertension and heart disease.
Curbing these potential risks by eliminating the need for immunosuppression can extend the life of a donated organ. Potentially, “it is one kidney for life,” Dr. Veale says. That can have a significant impact for patients. Currently, 20% of patients on the list to receive a deceased-donor kidney are waiting for their second, third, or even fourth, organ. “Every time a patient requires a retransplant, it makes it harder and harder to get a match. In addition, the surgery itself becomes more difficult because of the scar tissue,” Dr. Veale says. “If we can prolong survival of the initial graft, we make it possible for other people to receive a kidney, and we can bring down the number of patients who are waiting.”
Dr. Veale talks about the procedure, who might be a good candidate and how UCLA Health plans to advance transplantation tolerance in the future.
Dr. Veale: This protocol brings together four departments that generally don’t overlap: urology, medicine (nephrology and bonemarrow transplantation), radiation oncology and pathology. The procedure begins with extraction of stem cells from the bone marrow and blood of a well-matched donor. These stem cells will be processed and, after the recipient has received the donor organ and undergone a series of total lymphoid irradiation treatments, infused into the recipient. This infusion of the donor’s stem cells promotes mixed chimerism, the blending of the donor’s and recipient’s immune systems to prime the recipient to recognize, rather than reject, the new organ. Once chimerism forms, the organ recipient can wean off immunosuppression drugs.
Dr. Veale: Right now, it is well-matched family members. The procedures we have done thus far involve sibling pairs. But we now have approval from the Food and Drug Administration to perform the procedure with mismatched pairs as well. UCLA is not the first center to perform this procedure with well-matched sibling pairs, but we currently are the only one doing it.
Dr. Veale: It needs to be someplace that has the infrastructure to support something like this. It requires so many different elements. UCLA has all the big pieces in place that we need. A special infusion center? UCLA has it. Cryopreservation? UCLA has it. Pheresis? UCLA has it. Advanced radiation-oncology technology? UCLA has it. UCLA’s is the largest transplant program in the United States. We have all the components that are necessary to make this transplant-tolerance protocol a success. And there is such a spark among the people who are involved, such passion. When we see the patients who already have undergone the procedure, how grateful they are and how well they’re doing, it gives us all some extra juice and excitement for the future.
Dr. Veale: This is where I think UCLA will make a real difference. Up until now, tolerance has been limited to living donors. We believe we can be the ones who will move the field forward to make the leap to tolerance with deceased-donor organs. That is where the big difference will be made. Deceased donors accounted for more than 77% of the 22,800 kidney transplants that were performed nationally in 2020. That’s why OneLegacy Foundation and its CEO, Tom Mone, are working with us — they provided us with significant funding to support this effort. We want to see tolerance move from living donation to deceased donation. We would probably start with deceased-donor kidneys. Then, theoretically, we can move to other solid organs: liver, heart and potentially lungs. But also, to other areas that now are limited by immunosuppression medications, like vascular composite allograft transplantation, which would include hand, foot, uterus and face transplants. Those transplantations require very high levels of immunosuppression. If we can achieve tolerance with this group of patients, even if we aren’t able to get them down 100% to no immunosuppression, we might be able to get them to immunosuppression levels that aren’t so toxic.