A recent grant from the Department of Defense (DoD) to The Children’s Hospital of Philadelphia will fund a new study of advanced transplantation techniques. The study, which is being led by Children’s Hospital’s Wayne Hancock, MBBS, PhD, FRCPA, will focus on vascularized composite allotransplantation (VCA), a type of transplantation in which multiple tissues — such as an entire hand — are transplanted “as a functional unit,” according to the American Society of Transplantation (AST). In particular, Dr. Hancock and his team will be working to develop “new approaches to immunosuppression,” he said.
Dr. Hancock, the chief of Children’s Hospital’s Division of Transplant Immunology, will act as the project’s principle investigator, while L. Scott Levin, MD, FACS, the Paul B. Magnuson Professor of Bone and Joint Surgery at the University of Pennsylvania, will lead the University of Pennsylvania’s efforts. In addition to Drs. Hancock and Levin, Assistant Professor of Surgery at the University of Pennsylvania Matthew H. Levine, MD, PhD, will contribute to the investigation.
With this four-year, $2 million grant, CHOP and Penn join a consortium of institutions — including the University of Maryland and the Christine M. Kleinert Institute for Hand and Microsurgery — led by Emory University that will examine advanced transplantation techniques through the DoD’s Restorative Transplantation Research program. Overall, the research program seeks to “make a significant impact on improving the function, wellness, and overall quality of life” for wounded members of the military.
A study published last year in the Medical Surveillance Monthly Report, a publication of the Armed Forces Surveillance Center, underscores the DoD’s interest in advancing VCA. The study found that between 2000 and 2011, U.S. military service members underwent 6,144 “traumatic amputations.” Of these, about one third were “major amputations” of a hand or limb.
“Because of improvements in protective equipment and innovations in medical evacuation procedures and battlefield trauma care … many severely injured service members, who might have died in earlier wars/conflicts, survived their injuries with significant disabilities, including amputations,” the study’s authors note.
Weighing Transplantation’s Costs, Benefits
According to the AST, there have been a number of hand and face transplants over the last decade worldwide, with approximately 46 patients receiving 66 hand transplants. However, while clinicians can perform hand or limb transplants, whether they should is in question, as the burden of requiring ongoing immunosuppression when performing such transplants still outweighs their benefits, Dr. Hancock said.
This is because the effects of the immunosuppressive drugs that accompany any transplantation can outweigh the procedure’s benefit. After receiving a liver, kidney, heart or lung transplant, patients must agree to undertake a lifelong regimen of medications to prevent organ rejection, including the immunosuppressives tacrolimus or cyclosporine, mycophenolate, sirolimus, and steroids like prednisone.
There are a number of adverse effects associated with these drugs, which patients must take for the rest of their lives. For instance, some of the many side effects associated with tacrolimus are diarrhea, constipation, nausea, vomiting, dizziness, hypertension, liver and kidney issues, neuropathy, seizures, and depression.
In the case of organ transplants — without which one cannot live — the “risk-benefit ratio weighs in favor of taking the risk, because the benefit is one of life,” Dr. Hancock said. The ethics of performing a limb transplant remain less clear, he noted. And managing the body’s immune response to a transplant can be as tricky, if not trickier, than the surgery itself, Dr. Hancock pointed out.
So with this project Dr. Hancock and his team will work to “come up with some new strategies that don’t involve conventional immunosuppression.” The investigators’ work will begin in mice, eventually moving to humans once the researchers show that their ideas work. “We’re using knowledge that we’ve developed over years to show that we can do limb transplants in small animal models,” he said.
And though the project is not pediatric-specific, Dr. Hancock noted that it was “possible that the techniques developed could eventually be useful for limb transplants in kids.” Researchers might eventually be able to use what they learn to perform limb transplants on children with congenital limb abnormalities.
To learn more about The Children’s Hospital of Philadelphia’s transplant services and research, see the Pediatric Transplant Center.