If conventional reconstructive techniques are insufficient and transplantation is considered, Martin explained that transplant recipients must take lifelong medications that suppress their immune systems in order to prevent tissue rejection, and the ramifications of these lifetime immunosuppressants include significant health risks for patients that must be taken seriously.

“That’s kind of the holy grail,” said Martin of the immunosuppression issue. “That science is what could take this from an experimental, rarely performed operation to something that is much more routine and matter of fact.”

Unless the donor is an identical twin, the immune system must be suppressed to allow the body to accept the transplanted organ or tissue. And it’s even more difficult to do that in a face or hand transplant than with a solid organ transplant due to the complexity of the different types of tissue.

“When you’re talking about doing a composite tissue, like a face or a hand, it’s bone, fat, skin, muscle; those things involved are a pretty intricate mix of immunosuppression. It’s very difficult to allow the body to tolerate those kind of complex tissues, so it’s even more important for these composite tissues, face and hand, even more so than solid organ, to get that immunosuppression mix correct,” he said.

The upside of immunosuppression medications, Martin explained, is that the body tolerates the new tissue or organ, but the downside is that you’re blunting the body’s ability to reject infection or tumor. Additionally, the medications themselves can cause other complications, such as kidney and liver issues.

“For most of these transplants that are happening, both for face and hand, they’re on standard triple immunosuppression therapy,” he said. “There are a couple centers that are going into single-agent immunosuppression, which conceptually is a much better idea if you’re talking about long-term effects on the body. There isn’t, at this point, established ‘the’ one way to do it, so all centers are involved in transplantation research … Some are doing bone marrow transplants at the time of the organ transplantation to help the recipient’s body tolerate some of the new transplant tissue. We don’t have the answer yet, but probably most of the money and effort and research for both of these initiatives involve trying to find that way to make the body immunotolerant. That has not been achieved yet.”

Martin said the clinical results for patients who have received face transplantation are very good, citing return of their ability to animate the face, smile, speak, eat, and interact with society. “If you speak to those patients and see how they interact, they’re all exceedingly happy with their outcome,” he said.

“I don’t think in the next three to five years we’ll have solved the puzzle,” he said. “The body’s immune system is a fantastic, complicated system for a very good reason, because it’s so vital for us being able to live in a hostile world. To be able to solve a complex puzzle like that through a single breakthrough, I don’t anticipate that is going to happen. But I think with continued focused research, scientists will get better about trying to unlock some of the mysteries and make that a more acceptable answer.”

“Pretty much all of them, just because of the nature of the complex tissue, have episodes of rejection where you have to increase their meds, at least for a temporary basis, to allow that to be tolerated. That’s one of the things that we always have to keep mindful of. Just getting the operation completed, getting that patient out a couple years, where they have a functioning face, where they can re-engage with society and have that more meaningful existence, I think that’s one thing. That’s the feel-good piece,” Martin said.

The second piece, he pointed out, is the long-term follow-up. “You have to make sure that that patient always has a place that they’re going to be evaluated such that if they have these episodes of acute rejection, they’re seen promptly [and] can be treated. Just doing the operation and the initial round of medicines is one thing, but we can’t forget that this is a lifetime of vigilance. You can imagine the military patient who has one of these operations done, and then they exit the military, then they’re in the VA system, so we all have to work together to make sure this isn’t just an active military component; to make sure that that patient can be taken care of for a lifetime, either through the VA or through civilian centers.” 1

Although research is ongoing, Martin sees a solution to the immunosuppression issue realistically as a long-term prospect. “I don’t think in the next three to five years we’ll have solved the puzzle,” he said. “The body’s immune system is a fantastic, complicated system for a very good reason, because it’s so vital for us being able to live in a hostile world. To be able to solve a complex puzzle like that through a single breakthrough, I don’t anticipate that is going to happen. But I think with continued focused research, scientists will get better about trying to unlock some of the mysteries and make that a more acceptable answer.”

Martin also said the establishment of regional registries for patients and donors, so that traveling great distances to an isolated center isn’t their only option, combined with increased public awareness of the need for face and hand transplantation donors, are significant factors to advance these innovations.

Martin again emphasized that these government-funded initiatives will help both military and civilian populations. “Nothing really happens in a vacuum,” he said. “One of the misconceptions that a lot of folks have is looking at military medicine as some isolated branch of science and civilian medicine being something entirely different. [Because] all plastic surgeons in the military train in civilian [centers], we have that kind of cross-pollination and exchange of ideas and cultures. And especially in this scenario where a lot of the funding for face and hand transplantation is coming from government, DOD, and military dollars, the military and the government are very interested in this because it could be a way to repair some of the war trauma. Secondarily, we’re creating some potential candidates for this technology. If we can make it happen for some of these horrific injuries that happen around wartime, that’s all the better for civilian trauma patients, or cancer patients for that matter, who have a defect that can’t be fixed readily by conventional means.”

When asked about the biggest future challenges regarding these innovative procedures, Martin said, “I think funding will be, as we’re ending wars and drawing down the budget of the military. Paying for weapons systems and machines, troop levels, those are one thing. But when you look at how the funding pie is going to be divided, I think the easy, low-hanging fruit are some of these research initiatives.” He emphasized the need to “really state our case well and show the positive benefit of the DOD and government funding for this research and these initiatives.”

“Through financial support is how a lot of breakthroughs happen,” he continued. “I think if we reduce funding, my fear is we’re going to lose some of the gains we’ve gotten, certainly not push it down the road any further, so I’m hoping that that will not be curtailed to a significant degree. I think the science is there. I think we have to keep it in front of us to make sure we don’t ignore the gains we’ve already made.”

Martin said it’s impossible to foresee when the first wounded warrior will receive a face transplant. “I can’t imagine predicting if it’s going to be six months from now or one year from now or two years from now,” he said. “Certainly it’s going to happen.”

Martin expressed that one of the most extraordinary aspects of working with wounded warriors who are two-, three-, and four-limb amputees is to witness their spirit and what they will go through every day to heal and recover. One of the initial questions was, “Will that injured soldier or Marine continue with his active rehab, which is very painful and very arduous, knowing that he could have a near-magical hand transplantation one day? Will he try to work with his prosthetics; will he do his therapy?”

“The surprising answer is absolutely yes,” he continued. “Even though they have these potentially miraculous things, to watch those guys go through their physical and occupational therapy and to go through the arduous journey of using these prosthetics that are difficult to master but are very effective, there’s no give up in these guys … You can’t imagine a more deserving population to work for.”

 

1. There is an HA (Health Affairs) policy regarding participation of ADSMs (Active Duty Service Members) in non-cancer clinical trials such as those for face transplants. The NDAA (National Defense Authorization Act) provision that allowed retirees to have access to this benefit has “sunset,” so they are no longer eligible. A supplemental health care program waiver would need to be submitted and endorsed by the member’s service and approved by Assistant Secretary of Defense for Health Affairs Dr. Jonathan Woodson. Face transplants are not a TRICARE-covered benefit so would not be available to non-active duty beneficiaries.

This article first appeared in The Year in Veterans Affairs & Military Medicine: 2014-2015 Edition.