The world’s first human organ transplant in 1954 — of a kidney, from one identical twin to another — brought the 1990 Nobel Prize to Joseph Murray, MD, of Brigham and Women’s Hospital for this surgical achievement and his subsequent development of immunosuppressive drugs.
In the 65 years since, generations of Brigham physicians, surgeons, researchers and hopeful patients have continued to expand the boundaries of transplantation.
“We take on the most complex cases. If we don’t transplant them, they are not going to get transplanted,” said Anil K. Chandraker, MD, medical director of Kidney and Pancreas Transplantation and director of the hospital’s Schuster Family Transplantation Research Center.
Other Brigham historic firsts include the world’s first deceased donor transplant (1962), the first demonstrated effectiveness of cyclosporin A as an immunosuppressant (1979) and what is believed to be the first quadruple transplant of four organs (kidney, two lungs and heart) from a single donor to four recipients (2000).
“What makes us unique is that our multidisciplinary teams not only do the expert clinical work but also work at the cutting edge of basic and clinical research,” said Stefan G. Tullius, MD, PhD, chief of the Division of Transplant Surgery. Pioneering work continues in individualizing immunosuppression, treating patients with complex medical and immunological histories and making optimal use of all available donor organs.
Since performing the first full face transplant in the United States in 2011, Brigham and Women’s has performed nine (all successful) of the 15 full and partial face transplants nationwide. Rapidly evolving expertise, based on the hospital’s pioneering work in kidney transplantation, has enabled Brigham doctors to address even the most challenging cases.
When the hospital’s fifth face transplant patient developed anti-body mediated rejection, she did not respond to numerous attempts to halt the rejection. Her immune system had been highly sensitized from blood transfusions required to treat extensive injuries and burns from a domestic violence attack. Her physicians, emboldened by knowledge from decades of experience and research, offered to try a final, risky alternative to removing the transplanted face: a medication regimen that would shut down her immune system for weeks and leave her vulnerable to life-threatening infections. The grueling treatment worked, and the face transplant made possible substantial improvement to her quality of life for six years. Now, with small blood vessels injured by chronic rejection, she is listed for a second face transplant.
In another groundbreaking case, a Los Angeles man traveled to Brigham and Women’s in October 2019 where he became the oldest (age 68) person and the first black patient to receive a face transplant. A traumatic and fiery car crash six years earlier had led to more than 30 surgeries, but his lips, part of his nose and one ear were too ravaged for reconstruction. The Brigham transplant team and their patient opened new territory in this coast-to-coast case, as they waited for a matched donor with a similar skin tone. After the 16-hour procedure by a 45-person medical team, early results are showing return of some motor and sensory function, improving his ability to eat and drink, speak and smile.
These cases and others are helping experts worldwide learn about the lifespan of face transplantation and the long-term risk and benefits. To advance the field, the Brigham and Women’s physicians have reported widely on their experiences. Recently-published data on six patients at five years of follow-up showed a mean of 60 percent of maximal motor function over the five years; sensory improvement occurred only during the first year. Self-reported quality of life increased, and depression scores decreased. The authors noted that facial restoration provided adequate functionality to help patients’ social integration.
“Our previous experience has demonstrated that face transplantation is a viable option for patients with severe disfigurement and limited function who have no alternatives,” said Bohdan Pomahac, MD, director of the Plastic Surgery Transplantation Program. As the hospital continues to extend this treatment to more patients, he said, “we are exploring the ways in which we can quantify how much benefit our patients receive as well as identifying opportunities to limit the risks of this transplant through new immunosuppression protocols.”
To address today’s severe organ shortages, a collaboration between infectious disease physicians and transplant experts at Brigham and Women’s Hospital is expanding the donor pool by enabling transplantation from donors infected with hepatitis C (HCV).
In the largest clinical trial to date for transplantation of thoracic organs from HCV-infected donors, the Brigham’s multidisciplinary team reported 100 percent success for all 35 patients who received either a heart or lung from HCV-infected donors, followed immediately by a four-week antiviral treatment regimen. Six months after transplantation, all remained HCV-free and had functioning transplanted organs.
“If even half the other centers in the United States were to adopt the Brigham protocol, we would shorten the time to transplantation by nearly half,” said Mandeep Mehra, MD, medical director of the Heart & Vascular Center at Brigham and Women’s Hospital. Given the success of the trial, enrollment has continued. See video for more about this work.
As a society, we don’t sufficiently utilize all available organs, Dr. Tullius said. To make the best use of donor organs, he and others have researched and successfully transplanted older organs in age-matched recipients. “The immune response changes with age,” he explained. “By understanding this better, we can treat patients in a more individualized way, rather than taking the cookie cutter approach and always prescribing the same immunosuppressive treatment.”
Dr. Tullius also has advocated for expanding the use of deceased donor organs and those from donors at risk of infection, particularly if the patient might not survive the waiting time. “The patient on dialysis will always do worse than with a transplant,” Dr. Tullius said. In his related laboratory work, Tullius recently was approved for NIH funding to research techniques to rejuvenate donated organs and make them more resilient to injury.
Based on experience and expertise, the Brigham team is able to perform “A to B” transplants in which a patient with a B blood type, who has low anti-A titers, can be successfully transplanted with an organ from an A donor.
Today, the Transplantation Research Center in the Division of Renal Medicine has seven principal investigators involved in a broad array of translational and clinical research, including Dr. Chandraker, whose research has focused on regulatory T cells in solid organ transplantation.
Challenges ahead for transplantation include medical ones (including toxicity of immunosuppressive drugs, recurrent disease post-transplantation, ischemic injury of donor organs) and those relating to policies to address the organ shortage, regulation and FDA approval of novel therapies.
Through leadership in national and international organizations, Brigham and Women’s transplantation experts are continuing to shape the conversation around the moral, ethical and policy implications of what is possible. Dr. Tullius, current senior treasurer of The Transplantation Society, has also served on the board of directors of the United Network for Organ Sharing (UNOS). Dr. Chandraker recently completed a term as president of the American Society of Transplantation (AST), one of 11 Society presidents to date who worked or trained at the Brigham. Dr. Pomahac is president-elect of the American Society for Reconstructive Transplantation (ASRT) and incoming chair of the Vascularized Composite Allograft Transplantation Committee at UNOS.
Dr. Chandraker and other members of an AST task force on transplant metrics recently called for reform of current quality metrics (one-year patient and graft survival) that inform patient choice and access to transplantation — a topic that Brigham colleagues also tackled in a provocative essay in the New England Journal of Medicine.
Through research, teaching and advocacy, alongside groundbreaking clinical care, the Brigham’s tradition of leadership in transplantation is focused on the future. “The retrospective view of history is not sufficient,” Dr. Tullius said. “We live the history and build on it.”
