Dixon Kaufman, MD, PhD, Transplant Surgeon, Medical Director of the Transplant Service Line at UW Health, Surgical Director of the Kidney Transplant Program, Chair of the Division of Transplantation in the Department of Surgery at the University of Wisconsin School of Medicine and Public Health, talks about organ transplantation and the research being done to try and reduce the mount of post-transplant anti-rejection medications necessary for patients to thrive after an organ transplant.
Now we’ve got to talk about Barb. Barb actually got two transplants, right?
Dr. Kaufman: That is right.
All right. Tell me what happened with her.
Dr. Kaufman: Yeah. She was in need of a transplant because of some underlying kidney disease that only a transplant could really cure other than dialysis. And her sister wanted to donate a kidney to her. We ran tests to see how well matched they were perfectly matched. Because of that, her sister could qualify as a donor; Barb was a perfect recipient. We were beginning this new clinical trial in conjunction with other centers around the country. Though we were sort of leading the way because we got things organized very quickly, when they came forward for transplant, we arranged for the dual transplant which includes the kidney and some hematopoietic stem cells cells from her sister. The hematopoietic stem cells cells are circulating in the bloodstream. She had to undergo a special procedure about eight weeks before the transplant was scheduled to remove those hematopoietic stem cells cells out of the blood, get them collected, get them processed, qualified for being able to come back as an infusion about 11 days after her kidney transplant. They were actually frozen down and saved. They were banked until they were ready to be infused.
And then from there what happened?
Dr. Kaufman: Then when it was time for the transplant; both Barb and her sister are in adjacent operating rooms — side by side. The procedure to take the kidney out of her sister starts first. Shortly thereafter we bring Barb into her room and begin the exposure of the vessels on her. When the kidney comes out it is then literally taken into the operating room where Barb is, it is transplanted, that is put into place, and the surgery completed And then the kidney takes; it starts working. Barb is in the hospital for a few days. She has to undergo some special treatment called total lymphoid irradiation on a daily basis which is kind of like getting a real strong body x-ray to condition her immune system. She gets her anti-rejection medicines, and then on day 11 she comes back and her sister’s hematopoietic stem cells cells that are in an I.V. bag, they’re thawed. Then an I.V. is put into her hand and they’re literally just running through the I.V. into her bloodstream where they circulate in her body and graft and take. Some of the cells, the immune cells, start to multiply so she has not only the kidney from her sister but a little bit of her sister’s immune system. We call that phenomenon chimerism. And that’s where you have a dual immune system about 90% your own and maybe 10% or less of the donor and the immune systems intermingle. They regulate one another so that they leave the kidney alone. Then we followed Barb over the course of a year, testing for the continuation of chimerism, making sure there’s no rejection, making sure there’s no infection. As she reaches certain milestones, we start to eliminate her anti-rejection medicines. At three months we took her off one medicine and then at six months we started weaning her off the last medicine. By one year she would come off completely. And that’s where she currently stands.
No medicine at all?
Dr. Kaufman: No anti-rejection medicines. She’s on some medicines to help her blood pressure, some Vitamin D, and a baby aspirin. But her medication list is as short of a medication list that I’ve ever seen in any transplant recipient.
That’s amazing. It’s just amazing that it’s working.
Dr. Kaufman: It’s because her sister and her are very well matched. And it’s the start of hopefully a long progression of trials that will allow more and more people to, if not completely eliminate the medicines, significantly reduce them.
And explain why that’s important? Because the medicines themselves cause problems?
Dr. Kaufman: The medicines are a double-edged sword. They are miracle drugs that make transplantation possible for tens of thousands of people per year and without those medicines it would not be possible. But the medicines themselves suppress the immune system; some of them are actually hard on the kidney itself or hard on the body in other ways. And like everything, there are pluses and minuses and the medicines do have some negative effects. But it’s worth it to get a transplant. But if you can have the transplant with minimal to no anti-rejection medicines, that’s the best possible outcome we can think of.
It’s like the best of both worlds.
Dr. Kaufman: It’s the best of both worlds. We’re kind of in a new era now where for many, many years we were just trying to develop the best and safest medications. And they’ve never been better or safer. Now we want to minimize those medications by training and manipulating the intrinsic immune system of our recipients so that they’re less active against the organ that is in them.
And that’s one of the problems with a transplant is that your own system starts to attack the organ?
Dr. Kaufman: Yeah. Our immune systems are really important for our own survival. Without it there would be no life itself. They protect us from all sorts of things like infections and they actually help us surveil and fight off cancer. But it also will take out an organ transplant which is a good thing to have in place. So we’ve had to learn how to manipulate the immune system with medicines. Now we’re trying to learn how to manipulate it intrinsically through its own regulatory mechanisms. And one method of doing so is chimerism and the dual immune system.
And this is new. This is pretty cutting edge right?
Dr. Kaufman: It is relatively new in the whole field of transplantation. What’s especially new is that many of these have started in a single center that have pioneered some of this work. This particular study has gone from a single center to a multi-center study. So multiple centers, ours and many others around the country, are all doing this together to see if the promising results at a single center is translated to multiple centers. And if so, can be broadly applied to more and more patients.
I mean for Barb it’s a game changer. It’s a life changer for her.
Dr. Kaufman: This is the start of hopefully many, many years if not decades of perfect health without the anti-rejection medicines and a new kidney. But she, herself, and her sister in a way are sort of pioneers in this because it’s new uncharted territory. There are certain uncertainties that she and her sister were willing to go forward. So we have a lot of admiration for that kind of commitment. And we have a really great and strong team here to help her. We’re very experienced with clinical trials. I think we have mutual confidence in one another that we can do well by her. And we’re on this journey together; we’re just really getting started.
Love it. I guess you’ve probably done trials before. I mean, how long have you been doing transplants?
Dr. Kaufman: I’ve been doing transplants more than 25 years. And I’ve been doing trials for almost that whole time. But what’s different about this trial is we are reducing and eliminating medicines. All the other trials have been is testing new and actually stronger medicines to make the outcomes of transplant better. This one is the other side of the coin. How do we reduce and minimize the medicines so that people can live a healthy life with fewer anti-rejection?
How does it feel to be a part of a project like that?
Dr. Kaufman: Well I’m a team-spirited person and I really like the involvement of the pioneers that came before us here who I’ve actually worked with on other projects that are what we call preclinical projects. But then to be part of a multi-center national consortium of centers doing this in a project that the field could only dream about because it hasn’t worked very well in the past even though people have attempted it. And we’re finally getting a toehold on at least one method by which we can induce tolerance. There may be many others out there in the future but to begin doing this with a lot of other collaborators is very gratifying. And it’s fantastic to see how well patients are doing; that’s why we’re in this in the first place.
So the hope then is that in the future you’d be able to extrapolate it out to people who weren’t perfect match…
Dr. Kaufman: Yes. Barb and her sister were a perfect what we call HLA match. Some people are half perfect, if you will. And that’s kind of the next step. But that opens it up to a lot more people. And each step of the way we learn more and more; there are also people out there with a transplant from a perfect match that are still on medicines. Might they be in the future candidates for this kind of chimerism study? I think the answer is yes. There’s hope for people who’ve already had a transplant, and there’s kind of a new way of thinking for select people that are well-matched getting the transplant for the first time.
Yeah. That’s really exciting stuff. So it’s a fairly small study, it’s in a few other centers?
Dr. Kaufman: Yes.
Who’s funding the study? Do you know?
Dr. Kaufman: Yeah. This is funded by a company that is specializing in the cell processing of the stem cells from the donor; they are called Meteor Therapeutics. This is the first study that they have rolled out called the Mercury Study. And it’s a relatively small pioneering study with a few select centers.
And then are you directly compensated at all? Or is the hospital?
Dr. Kaufman: I was asked before all this got started because I have knowledge in this area to be on their advisory board. I agreed to be on their advisory board but I did not agree to take any compensation. And as we got more involved they kind of wanted me to sort of be the team leader of this study and I thought I should kind of come off their advisory board just so there’s an arm’s length. I don’t know if my picture is on their website anymore or not but I really don’t have any financial or any other conflict of interest, sort of entanglements if you will, with them.
And then and even if you were you would probably still recommend or still be involved because you – I mean it’s a good thing for you to be involved with?
Dr. Kaufman: Yeah, I mean I really believe in it. One thing that you’re not aware of, but for the past seven to eight years I’ve been working with the pioneering group at Stanford in a large animal preclinical model exactly doing the same things in more widely-disparate donor recipient combinations to help move the field forward. We’re doing it in large animals before it comes to humans. I’ve been involved in this field for a long, long time. We just haven’t done it here in humans in a real clinical trial. So this is a long arc and there’s sort of that background that I have in this field. It’s really gratifying to see how basic research, translational research, large animal preclinical models, all funded by our National Institutes of Health, get translated and applied to saving people’s lives.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information please contact:
Dixon Kaufman
Gian Galassi
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