Dr. Joseph W. Turek, MD, PhD, MBA, Chief of Pediatric Cardiac Surgery at Duke University, and executive co-director of the Duke Pediatric Congenital Heart Center, talks about a “first-in-the-world” heart and thymus transplant that saved one little boy’s life.
Interview conducted by Ivanhoe Broadcast News in May 2022.
Can you explain what you’ve done in one patient?
TUREK: Yes. We had a patient that we had listed on the heart transplant list because he was six months old, and he had a heart that was not repairable. He had some leaky valves that we were not able to fix. He had a single ventricle heart, meaning he kind of had half. He had one of the two ventricles that you need for your heart to work. So, he was listed for heart transplantation. While he was on the heart transplant list, he kept getting these recurrent infections. We finally worked that up from an immunologic standpoint and we found out that he didn’t have T cells. So, T cells are something that are produced by the thymus. They help to fight infection. That was the reason why he was getting these recurrent infections. Duke happens to be the only place in the western hemisphere that does cultured thymus tissue implantation for kids in this similar situation that don’t have a functioning immune system or a functioning thymus to make these T cells. We thought, well, this is a real opportunity here. It’s an opportunity to not only give this patient a heart that he needs and was listed for but also a chance to reconstitute his immune system from the same donor. He needed both organs. We’re going to give him both organs. But they’re from the same donor, which adds this level of complexity to things. What it adds by taking it from the same donor is the possibility that that new cultured thymus tissue grows up in the environment of the new heart. So, it will be recognizing those things it’s growing up with because it’s creating its own immune system again itself. It keeps the body from rejecting this new transplanted heart.
Where’s the thymus? How does it prevent infections?
TUREK: The thymus sits on top of the heart. It’s interesting. When we do pediatric heart surgery, the thymus is in the way of a lot of what we’re trying to do. So, in a standard pediatric heart operation, we remove some of the thymus. We may remove up to three-quarters of a thymus because it’s in the way of what we’re trying to operate on, which is the heart and the aorta coming out of the heart. It used to be that that thymus tissue was discarded. But with Dr. Markert’s innovation – and she’s the one who developed this idea of culturing thymus and giving it to patients that needed the thymus. For 25 years, we’ve been keeping the thymus, giving it to them, allowing them to culture the thymus up and then use it for patients who don’t have an immune system.
Could you tell me a more about the discovery here at Duke and the thymus? Is the cell tissue engineered?
TUREK: It is. It was about 25 years or so ago. My research collaborator, Dr. Louise Markert, who’s an immunologist here and has been an immunologist here at Duke for some time, came up with the concept that if we were able to take some of the discarded thymus from pediatric heart operations and use that thymus in some way to reconstitute an immune system. However, the problem is when you take a fresh thymus from a donor, it has in there these T cells that are already formed, this immune system that’s already formed against what it recognizes as self and what it recognizes as foreign. So, the idea is that you want to use the machinery of the thymus gland. You want to use the machinery of that. But what you don’t want to do is you don’t want to have these already preformed T cells in there that could potentially attack this body that they’re being implanted into. So, the way you do that is you keep the scaffolding of the thymus by taking fresh thymus in culturing it. So, you put it in a tissue culture environment. Grow it up. It grows into many pieces of cultured thymic tissue that no longer have these preformed T cells in them. Now, it’s just this machinery. It’s this scaffolding that can start to develop new T cells that will be specific to the patients that they go into.
Is this patient the very first time you’ve done both the heart and thymus surgery?
TUREK: It’s the first time in the world that both of these have been done together.
Can you describe how the procedure went? How did you and your colleagues perform this?
TUREK: The procedure went very well. It’s interesting when you look at the timeline on this. We received a donor. We had to get emergency approval from the FDA in order to do so. Then, once we had that – and they felt like this was the best thing for the child. The child needed a new immune system. Clearly needed a heart as well. This gave us an opportunity to do both of these together. We procured the heart and the thymus at the same time from the same donor. We brought it back. Now the heart needs to be transplanted in a definitive period of time or that heart muscle will not be viable. So, you really want to get a heart sewn in within four hours of the time that you take it out of the donor. We brought the heart back with the thymus and we implanted the heart within that four-hour period. Now, the thymus itself with this culturing technique, it takes two weeks to culture the thymus so that it’s ready to be implanted. We took the thymus, dropped it off at the facility where we culture the thymus. Cultured it for two weeks. By this time, Easton was doing well from his heart transplant, and we went back to the operating room two weeks later. We did the cultured thymic tissue implantation.
How is Easton doing now?
TUREK: Oh, he’s doing great. I mean, he has really thrived. He did very well since his heart transplant. He was very debilitated. And if you talk to Easton’s family, there were some scary times there when he was on the heart transplant list. But he’s really flourished since his heart transplant. Then, his thymus implant, he’s now reconstituted his immune system. So, it’s very exciting. He’s got a functioning heart. He’s got a functioning immune system. And he was able to form that new immune system in the presence of the medications that we use for heart transplant, which no one knew about before if we could do that or not. That was definitely a hurdle that we’ve overcome with this particular situation.
What about the possibility of rejection?
TUREK: That’s where the Holy Grail is. The Holy Grail for any kind of transplantation, solid organ transplant, and not just the heart, is the idea that can you not get rejection without being on all these high doses of immunosuppression, which can be devastating to someone’s body – to your kidneys, to causing infection, to even causing cancers when you’re on these high-dose immunosuppressants. So, the idea is that, will this new immune system that he’s formed, does it recognize that heart itself? We think it does based upon some of the studies that we’ve done in the laboratory. We’re going to find that out soon enough as we start to peel back on the amount of immunosuppression that Easton’s having right now.
Does he have some right now?
TUREK: He still has immunosuppression. But we’re about to the point – because we’re happy now that the immune system has reconstituted itself, I think we’re about ready to start peeling back on some of these medications. Yes.
How long could the new organ last? Will Easton, at some point in his life, be a candidate for another heart transplant or for some other measure?
TUREK: A lot of people don’t realize that many organs have different lifespans to them. A heart transplant in the U.S. has about a 10-to-15-year lifespan before you need to get a new organ. That’s because you have these episodes of rejection over time that occur. What we’re thinking is if he truly is tolerant to his heart, meaning he recognized that heart itself, he shouldn’t have these micro episodes of rejection over time. In fact, the promise is that organ could last decades more time. So, that’s the real hope here is that we can have hearts that last like yours or mine in a patient who received it as a transplant.
Under what conditions is this an appropriate and a saving procedure? Have you done any other since then? Or was it a very specific set of circumstances that made Easton the best candidate?
TUREK: Well, it’s difficult to make that leap into the clinical practice. We’re doing all this type of work in the laboratory right now. The thing that Easton had going for him is his immune system was incompetent. That allowed us to think that this was the best thing for him. It wasn’t putting it in someone who had a competent immune system who could potentially have a higher chance of rejecting this type of therapy. So, I think it’s a very rare individual that would need this at this point. But the promise of this is that we can translate this eventually with some more work in the laboratory to those people with competent – like most people, immune systems.
What is the next step? Does this also show promise for the transplantation of other organs?
TUREK: It does. It’s something that could affect all solid organ transplants. Now, it makes sense that it started with the heart and our research started with the heart. That’s because we have to take out the recipient’s thymus. We don’t want their own thymus competing. Now, granted, Easton didn’t have a functional thymus. We didn’t have to worry about that as much, although we did take out the thymus that he had. But in patients that have competent immune systems, you would have to take out their thymus. So, you are in their chest anyway, so it makes a lot more sense to combine this, at least initially with heart transplant, where we’re in the chest or even lung transplantation where we’re in the chest also.
How often does he come back in? How closely is he monitored right now?
TUREK: We have a regimen that we monitor him with based upon our agreement with the IRB ( internal review board) and the FDA. He’s monitored at least monthly with multiple labs looking at his T cell enumeration. I think we’ll probably ramp that up a little bit as we start to pull back on some of his medication for rejection.
What goes through your mind every time you see this little guy coming in?
TUREK: Well, it’s really a miracle. I think the main thing that I see when I look at him and he’s there with his family is how courageous they were to make that step and to agree to try this. Now, they were in a tough situation. And Easton, like I said earlier, many times, it looked as if he wasn’t going to make it through his hospital stay before he got his transplantation. But when I presented this to them and they realized that it could help their son, it seemed to me that they thought it was more important that they could potentially help thousands of people down the road if this were successful.
Is there anything else that you’d want other people to know about this procedure?
TUREK: Yeah. I think the thing I’d like to say is that this has taken a ton of research. We’ve had a number of collaborators who have been part of this and doing this research for 25, 30 years here at Duke and around the world as well, doing this thymic research. This is a really exciting time in the world of transplantation. We’ve seen pig transplantation that’s occurring. This is a fun time to be involved in this because we’re moving the needle, and this is going to change the way that the transplants are done in the world.
END OF INTERVIEW
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