Posted: Monday, September 15, 2014 3:59 pm
MILWAUKEE, Wis. (Ivanhoe Newswire) — For patients who’ve had a heart transplant, the surgery is just the beginning. Patients must undergo dozens of tests and biopsies to check for rejection of the donor organ. This can be especially difficult on children. Now a new approach could change the way doctors predict transplant rejection, without expensive, invasive procedures.
Before age 2, Adam Trumble’s parents were told Adam needed a heart transplant.
Adam’s Parents, Timothy and Amy Trumble, told Ivanhoe, “It was hard to watch. He just kept getting sicker and sicker.” Adam’s heart stopped working, but an implanted pump helped him get strong enough for transplant.
Timothy and Amy told Ivanhoe, “It was a 6 year olds heart.” That gift saved Adam’s life, but now he faces another risk. Michael Mitchell, MD, of Children’s Hospital of Wisconsin, told Ivanhoe, “15% of all patients per year have rejection of their heart.”
Yearly heart biopsies test for rejection, but it’s not tough on patients.
Steven Zangwill, MD, of Children’s Hospital of Wisconsin, told Ivanhoe, “We bring these kids 5 or 6 times in the first year post-transplant. It’s an invasive procedure, not without risk.”
Now a new blood test developed by this team could replace biopsies.
Mitchell told Ivanhoe, “If you pick up rejection early, you can treat it with a prednisone that can be administered at home.”
The test works by looking at the DNA in the blood. The amount of donor DNA in the blood is a clear indicator if or when rejection is beginning.
Mitchell said, “If you pick up rejection early, you can treat it with a prednisone that can be administered at home.” Now 7, Adam takes 3 days to recover from his annual biopsy. A blood test could keep him in the game and able to handle whatever gets thrown his way.
Prednisone costs around $6, while Mitchell says a trip to the hospital with heart rejection can be more than two million dollars for the hospital stay alone. The results from the pilot trial found the blood test to be 100 percent sensitive. It is now being tested in medical centers nationwide. HEART TRANSPLANTATION: When a heart becomes diseased or damaged in any way, it may need to be replaced with a healthy donor heart which must be matched as perfectly as possible to the heart of the patient receiving the transplant. During the procedure, a cut is made through the patient’s breastbone. The diseased heart is removed while a bypass machine continues the blood flow through the veins. Once the new donor heart is stitched in, tubes are inserted to drain blood, air and fluid out of the chest for several days after the procedure.
RISKS: There are many serious risks that are associated with performing a heart transplant. Some of the major risks include: * Severe coronary artery disease * Blood clots * Damage to the kidneys, liver, or other organs from anti-rejection medications * Rejection of the newly implanted heart
(Source: http://www.nlm.nih.gov/medlineplus/ency/article/003003.htm) NEW TECHNOLOGY: Heart transplants don’t just end at the surgery. Patients must undergo numerous tests afterward in order to check if the donor heart is being rejected by the patient’s body. Patients undergo yearly biopsies that remove a piece of tissue or cells to test for rejection but can be painful for the patient. Doctors are now using a new blood test that they hope can soon replace these biopsies. The new test uses a cell-free DNA approach to look for DNA variations. This allows for earlier detection of the donor’s DNA in the recipient’s blood; an indicator of possible organ rejection. This blood test is not only easier on the patient but far less costly as well. The test is being conducted across the country and has shown promising results thus far.
Dr. Michael Mitchell, M.D., Pediatric Cardiothoracic Surgeon. Can you talk about the need for the test that you’ve developed?
Dr. Mitchell: Sure. In the field of heart transplantation which is a very important intervention for many children and adults in this country and around the world, one of the key determinants of early outcomes and the determinant of long-term outcomes is the issue of rejection. 15 percent of all patients per year have rejection of their heart and if you can treat rejection early you make a significant difference in the longevity of the organ and the life of the patient who’s received the organ. In addition, there is no good noninvasive way of screening for rejection currently available. What’s required is something we call endomyocardial biopsy. Patients who’ve received a heart transplant have to go to the catheterization laboratory and have a catheter that’s placed in their vein and then winds its way up into the heart. Then a bioptome comes and takes a bite out of a piece of the myocardium to assay for rejection. This has to be done multiple times in order to pick up rejection you have to do it frequently. The procedure is invasive and costs a lot of money and it has a risk of complication. It also has a chance of missing rejection because rejection itself is a patchy process which doesn’t necessarily involve the entire organ but can involve sections of the organ and so a biopsy can miss an area that’s affected. For all those reasons there’s a real need to have a noninvasive test which is very accurate and very sensitive. In pediatrics it’s particularly important because children who’ve receive heart transplants just don’t have vessels that are big enough to receive these biopsies as frequently or as easily as can be accomplished if they were bigger. Many of the children have lost vascular access so there’s no good way to biopsy them and survey for rejection. We really came up with the idea of doing this in the context of a particular need and a particular patient who just had no vascular access.
I would think it would be more difficult with children.
Dr. Mitchell: That’s right and the biopsy procedure requires that the children are put to sleep completely. It’s a big deal to undergo that. If you were to have a test which was sensitive enough to replace biopsy it would change their lives.
The family we’re going to speak with, their child is actually allergic to anesthesia though so it even makes a more problematic for him.
Dr. Mitchell: Yes and there are many, many children like that who either have problems with anesthesia or who just don’t have the vascular access so they can’t tolerate the procedure. How does the new test work?
Dr. Mitchell: The new test is a simple blood draw that can be done just from a peripheral vein and it can be done frequently. What is looked for in the blood is something that’s called circulating cell free DNA. So it turns out that in all of us we have small fragments of DNA that are outside of cells that circulate in our bloodstream and are cleared. The origin of that DNA varies if you’re a pregnant woman then some of that comes from your fetus. If you’re a person who has cancer then a component of that comes from cancer and if you’re a person that’s received a heart transplantation or any solid organ transplantation, a percentage of your circulating DNA comes from the donor origin. What we do is precisely quantify the amount of DNA that’s from the donor origin and we found that very small changes in that amount of circulating donor specific cell free DNA are exquisitely sensitive for picking up injury to the donor organ. We can detect rejection on that basis.
So is this something that would replace the biopsy?
Dr. Mitchell: I think so. I think that initially it will be done instead of a biopsy and in the patient who would come back with positive test they may then go on to biopsy in a small segment of those patients. I think ultimately this will replace the biopsy. If the data in our multicenter studyis as convincing as the pilot data has been.
Can you tell me a little bit about the family that we’re going to be speaking in with?
Dr. Mitchell: Yes, this is a very special family and but not entirely atypical for patients who have congenital heart disease, this family required mechanical circulatory support in the form of both in ECMO and also a ventricular assist device prior to transplantation. It’s interesting because you get a sense of how many healthcare dollars and how much resources were actually applied to this particular patient in order to attempt to rehabilitate the heart and then to transition the patient safely to heart transplant. Then the child went on to receive a heart transplant which was very successful and transitioned off the ventricular assist device. Now in the hopes of preserving the longevity of this very precious organ Adam undergoes multiple biopsies to assay for rejection. That’s a problem for him as it is for all children and everyone who’s received a heart, particularly for children.
What does this mean to you to have developed something like this?
Dr. Mitchell: First of all it’s not just me, there’s a whole team of people who have gone in to the development of this. It’s really exciting because of teamwork and a group of people who have an interest in a compelling medical need that we were able to look at this. I think it’s exciting. We performed a pilot study combining the efforts of our clinicians here and the research scientists that we work with and the advances in science had positioned us so that we were in a very unique position in order to do this. When we got the results of our pilot study back and they were so convincing with a hundred percent sensitivity in picking up patients with rejection we were thrilled. Others were excited too and that has allowed us to raise money supported by the federal government through the NIH/NHLBI in order to perform a multicenter study to really ensure that this approach was as accurate as it seems to be. So how big of a breakthrough would you say this is?
Dr. Mitchell: I think that if the data from the multicenter studysupports our pilot data than it will be the kind of test that changes the field of transplantation. The real benefit of this approach is to preserve the life of the child who’s been through transplant. This really has multiplicative effects because the way in which this preserves the life of the patient who’s received the transplant organ is by early frequent monitoring for rejection and then allowing early treatment of rejection. That will preserve the function for this particular child or adult who has received the heart. In addition, by preserving that organ for this patient you preserve the next organ for the next patient in line. It’s a very precious resource, a donor organ and particularly a donor heart, and so preserving these organs is critically important and really has a multiplicative effect for the field. There’s a real financial impact here as well which is important. I think the treatment that we’re proposing if you pick up rejection early you can treat it with prednisone that can be administered at home. $6.22 is the typical cost for a course of this. For a patient who’s admitted to the hospital with rejection, the dollar figures are staggering. They end up being between half a million and two and a half million dollars for the hospitalization of a single patient alone. When you get up to the real higher numbers you’re talking about someone with severe rejection and that can result in the need for additional mechanical circulatory support and even death of the patient. So there’s actually a big financial downside to missing rejection.
So this test is huge.
Dr. Mitchell: I think it can make a real difference in this field of transplant.
So you said it’s about 15 percent of patients experience rejection?
Dr. Mitchell: Yes it’s a little bit higher than that so the first year following transplantation it’s probably around 20 percent for cardiac transplant and then it drops to around 15 percent as a baseline incidence of rejection for the rest of that patient’s life.
You were talking a little bit before when you first saw this coming out on the market, did you say two years? Dr. Mitchell: Well I think it’s conceivable that it could hit the clinics in a number of years. We would not want to rush this to the clinics before it was established that indeed it was a superior approach. We don’t have that data yet. We’re dependent on our multicenter study to really look at this and it would only be appropriate to take it to the clinics once there was assurance that it was as good as the pilot looks. I would say between two and four years would be a reasonable time to introduce it to the clinics.
So let’s say a child was coming in and was going to have a transplant. You would do the blood test prior to and then continue giving that test if you thought there was a risk of rejection or is it just in one time?
Dr. Mitchell: All children and all adults who have heart transplant are at risk for rejection. This is a test that would be appropriate for people after they’ve received their heart transplant. The first week following transplant patients are at the highest risk for early rejection but that risk persists throughout the first year at a very high level. If it’s a noninvasive test like this it would be appropriate to do it frequently so I would anticipate even monthly testing or even more frequently than monthly testing may be beneficial. So it would work just like a biopsy except you don’t have to go through doing that?
Dr. Mitchell: You don’t have to go through a biopsy. Since it’s noninvasive you are actually able to do more frequent surveillance which I think is a really important point because we’re doing these biopsies to pick up the patient before they become symptomatic. The more frequently you can do the assay within reason then the more likelihood you’ll pick up rejection early and can treat it easily with a dose of oral prednisone therapy or oral steroids at home. Anything else you’d like to add?
Dr. Mitchell: One of the impacts is really the potential of saving the function of the organs for other patients. It’s a precious resource once you’ve received a heart transplant. So much effort goes into it and so much financial resources go into this patient. It really saves the life of the patient. If the rejection occurs and is treated late then you get injury to the organ that’s not readily reversible, not completely back to baseline, and over time that really adds up. If you can preserve an organ by treating it early for rejection, then you preserve that organ for that patient and you preserve another organ for another patient. So it has a real multiplicative effect to the field.