Quality of life is crucial when considering options for a patient with severe hand or upper extremity in­jury. With a rapidly expanding range of approaches, Johns Hopkins specialists are increasingly able to tailor treatment to a patient’s preference and medical situation, restoring as much as possible of the patient’s life.

For patients with appropriate medical, psychological, and social in­dicators, a hand or upper limb transplant is becoming an ever more viable option. The team of W. P. Andrew Lee, Jaimie Shores, Gerald Brandacher, and their colleagues is setting a standard in this new field. Having transplanted 10 limbs across six patients (including the only two above-elbow transplants in the United States), the team members have some of the most extensive experience in the world. And, based on that experience, they have developed advanced methods that will likely make transplantation available to even more patients.

While transplantation is a complex procedure (which involves add­ing new skeletal and soft tissues, re-routing nerves, and reconnecting blood vessels), its greatest limiting factor is the patient’s tolerance of the immunosuppression treatment that is required. Because the sur­gery isn’t lifesaving, subjecting patients to the rigors of standard triple-drug immunosuppression for a lifetime has the potential to do more harm than good.

So Brandacher helped design—and is constantly refining—a groundbreaking protocol of minimal immunosuppression. Such a shift in the risk-benefit ratio brings limb transplanta­tion into reach for more patients and also offers possible benefits for solid organ transplant recipient.

“Because side effects and drug toxicities are minimized, this protocol could open up the field of extremity transplantation to become more mainstream,” says Brandacher.

The gentler protocol involves an antibody to deplete immune cells at the time of transplan­tation, followed by a single immunosuppressive agent at low levels immediately after surgery. Two weeks later, bone marrow cells from the donor are infused to modulate—rather than indiscriminately suppress—the recipient immune system, helping the recipient tolerate the graft with minimal medication.

“There are other centers in the world that perform hand and face transplants, but our pro­gram is unique in using an immuno-modulatory protocol that minimizes the side effects of medications for the transplant recipients. We believe it is a critical aspect to make these types of transplants widespread,” Lee says.

Another limiting factor in upper extremity restoration is nerve regeneration. Surgeons can transplant a limb, but if the nerves don’t grow back into the muscles robustly, the limb won’t function adequately. A concomitant effect of the main immunotherapy drug in Brandacher’s protocol is that it helps stimulate nerve regeneration.

“If the nerve regeneration problem was eliminated, it would expand the pool of candidates for transplantation for upper extremity and may open the door for lower extremity as well,” Shores says. “The advances we make for hand transplants not only benefit our program, but may benefit all types of transplants.”