M. D. Anderson Cancer Center
Cancer Newsline Audio Podcast Series
Date: September 29, 2008
Duration: 0 / 17:48
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Welcome to Cancer Newsline a weekly podcast series from The University of Texas M. D. Anderson Cancer Center in Houston TX. The aim of Cancer Newsline is to help you stay current with the news on cancer research, and the rapidly changing advances in cancer diagnosis, treatment and prevention and provide you with the latest information on reducing your family’s risk of being diagnosed with cancer. My name is Doctor Leonard Zwelling I am a professor of medicine and pharmacology here at M. D. Anderson.
Today we will be talking with Dr. E.J. Shpall professor of medicine in the Department of Stem Cell Transplantation and Cellular Therapy and Dr. Laurence Cooper associate professor of Pediatrics in the Children’s Cancer Hospital at M. D. Anderson and Chief of the Cell Therapy section in the, Division of Pediatrics. What we will be talking about today is stem cells, their use in bone marrow transplantation and the availability of stem cells through donated and banked umbilical cord blood.
Dr. Shpall lets start with the obvious question. What is a stem cell?
Well, a stem cell is a very primitive cell that comes from the bone marrow originally and it is a cell that can stay very primitive or divide and make things that are more mature that we need to live. So a marrow stem cell ultimately divides and makes platelets to keep us from bleeding it makes red cells to carry oxygen it makes white cells to fight infection and to produce immune cells that keeps the immune systems healthy.
Now why umbilical cord blood? This is something a little bit newer then the traditional bone marrow transplantation. Why it is such a useful source of stem cells?
So many years ago, decades ago we started doing stem cell transplantation with bone marrow and bone marrow works well and preferred blood works well and if you can find a donor for a patient with bone marrow, it’s a standard of care transplant in this day and age. The problem is our first choice is that transplanters always to find a donor in the family and there is normally one in four patients that will have a member in the family because of the gene pool and how the genes combine you need to match the HLA markers the unique marker on your blood in order to have a safe transplant. And so one in four in the family will match. We therefore increasingly over the past decade and a half have been going outside the family there is a national marrow donor registry. Where 7 million donors have registered to donate their cells and they do it everyday. You can often find a donor in the registry for your patient which is also very good source of hematopoic support. The problem is if your white, Caucasian we find the donors 80% of the time, but if your any type of ethnic minority African American, Hispanic, Asian, interestingly Jewish. We do not find donors readily in the registry. It’s multi factorial, the reason that we don’t reason number one minorities don’t seem to donate readily and number two for certain of the ethic groups particularly African Americans they have a more complicated gene pool that makes it more difficult to match. So that you need more donors available to find matches then for other races.
So is that where the umbilical cord blood comes in?
Umbilical cord blood came on the scene in 1988 the first transplant was done. When Dr. Gluckman… Eliane Gluckman from France realized when you take a quart of blood from the umbilical cord and transplant to patient because it’s very rich in the stem cells that are in the marrow and when that worked several things became clear. Number one you can start banking cords all over the world that had ethnic minorities so that cord banks go into hospitals where African Americans or Hispanics are born and they are increasing the inventory of those units rapidly. So there are more out there for minority patients and the most critical thing is that cord blood is more naïve it has fewer cells and fewer T-cells so it appears when you use cord you don’t have to have a specific HLA match as you do for marrow so where routinely in the marrows we have to have six out of six of the major antigens match. Were using four out of six with equal efficacies.
So it got more wiggle room, more common.
More common and you can go into an Asian hospital and have Asian cords. So at M. D. Anderson with the first three thousand transplants we did with marrow only 25% of our patients were minority. When you look at the couple hundred cord bloods we done, 59% are minorities. So we are clearly with this source of hematopoic support supporting a unmet need that we desperately had no options for in the past.
Dr. Cooper we heard a lot about embryonic stem cells back in 2001 when President Bush made his ruling with regard to their availability and for federal funds. What’s the difference between the stems cells were talking about here and those stem cells.
That’s a common source of confusion and the key difference is that the stem cells that Dr. Shpall described are harvested from essentially the babies blood. Right after birth, so the mom delivers, the cord is clamp and then cut. Then the blood is drained from the placenta after the baby is born safely wrapped and bundled it’s those cells that essentially in that placenta or in that blood pool that are then collected and stored ,frozen in the banks like M. D. Anderson. That is a source of hematopoic stem cells. Hematopoic being the word physicians use to describe the genesis of blood and blood components. Just like E.J. said, to make platelets to make white blood cells or type of immune cells and red blood cells. The embryonic stem cells are a completely different type of cell, it’s much more primitive. In fact they belong way back in the genesis of the child, in the embryo in the mommy’s womb. Way back in the beginning and it’s those stem cells that are much more complicated in terms of there ethical use, translation into medicine.
You want to make it clear that the ethics are quite different then ethics described.
Exactly! There is no risk to the baby or to the mom to collect umbilical cord blood.
Umbilical cord blood is an adult stem cell. It is one of the adult stem cells that’s cord marrow, peripheral blood.
So it has already started its pathway toward being blood.
It is definitely adult to distinguish it from the more primitive. What diseases are you using stem cell transplants for?
In pediatrics where a lot of the initial enthusiasm from cord blood transplant got going, we have two main types of patients that come to our service. Children with cancer with malignancies and children with non-malignancies with inherited diseases. So in cord blood actually been successful for both of these both as a way to deliver a new immune system to patients with cancer and importantly also to deliver a new source of hematopoic blood deriving stem cells for patients who had a inborn error either in there actual blood component. Some babies are born with a marrow that poorly functions can’t make platelets, can’t make red blood cells and we can resuscitate those children by infusing in this cord blood stem cells. Also very interesting blood stem cells when there put in have the ability to help correct some metabolic diseases, some enzyme diseases in children and that work has been started at Duke in many ways and now really has farmed out across the United States and across the world and as a standard of care. So if you have a number of malignant disease as well as non-malignant disease you will be eligible and would receive umbilical cord blood transplantation for cure.
Dr. Shpall, in the adult population, same source of diseases or different?
The adult population is primarily malignant diseases, hematologic malignant diseases high risk so acute leukemia, lymphoma, chronic lymphocytic leukemia, even CML -chronic myelogenous leukemia have fail hematinic type standards. Those are the main Non-Hodgkin’s and Hodgkin’s Disease are all very commonly treated with cord blood.
Is this looked upon as last ditch treatment or do you do it earlier then you use to?
So it’s moving up in the priority. It use to be a last ditch effort and now as our data is getting better, there are more cords available and the cords are getting better. Right now in our center if we can find a perfect ten out of ten donor in the registry. That’s still our first choice but absent that we will now take cord blood over a nine out of ten mismatched. Donor or other strategies we are often considering that to be acceptable. It has got more acceptable our data has got better and the results have got better.
Since this can be banked cause we talked about banking it. So you collect it and freeze it for later use. Should all families at the time where there children are born, bank the cord blood for later use?
That’s another really good question, so the Pediatrics Society actually have a position statement on this and the recommendation is yes family should bank cord blood but it should not be patient specific. So in other words if a mom comes into the hospital we would encourage that mom to donate for instance to Dr. Shpall’s bank and that’s an anonymous donation, that family would no longer have record about where that cord blood will be used but would have essentially given the gift of life because that bank can be drawn by Dr. Shpall or myself when we have a child or in my case an adult whose in need for an umbilical cord blood we will pull that cord that has been donated to the bank and infuse it into the patient.
Is there any cost to the patient for doing that?
No cost at all to a public bank. That is to make a distinction from the public bank and all the private banks which are aggressively trying to get business to have mothers pay to keep there units banked for themselves and that does cost anywhere from 1200 to 1800 dollars and a yearly fee. It’s very unlikely for the most part that these will ever be used. These are people whose families don’t necessarily have these cancer types.
Just to follow up, I think it’s important to point out that the quality of the cells that are stored in the private bank is not subject to the inspection and the level of rigor we apply to our own public banks. So using during transplant we are actually very nervous by using private banked cells. I think historically those cells have not performed as well as those families that have invested and put up money would have wanted.
Lot of them are very small, they don’t have the expertise.
One of the things that came up when I was reading about these things is the idea of manipulating these cells after there collected. Dr. Cooper you do this in your laboratory. Could we talk about the kinds of manipulation you can do can you expand the populations and why does that make it better?
This is where E.J. and I have an overlap, both in the scientific world and also moving this type of technology to the clinic. As E.J. pointed out, cord blood transplantation is really achieved as a platform technology now are secure in our ability to deliver cord blood cells to adults and kids. So the question is, can you do better? My world is one of essentially augmenting the immune response delivered from that cord blood inoculum. As E.J. pointed out, most parents know when a baby is born, the pediatrician says if that kid has an infection in the first couple of months in life, you've got to get that kid right to the doctors office, and the reason is the kid has a very immature immune system. So of course the cord blood that was collected at birth also has a very immature immune system. That has benefits, as we pointed out, in terms of being able to do transplants across HLA barriers, bring minorities into essential to receive this type of therapy but it also poses challenges for us immunologists because what we have to do is make sure those cord blood cell now put into the recipient grow up in a way that will keep that recipient safe. Grow up an immune system that will fight off infections but importantly fight off the underlying cancer. So that’s where my lab has really taken a strong position and we have used the power of gene therapy . Modifying the actual DNA content of the cord blood T-cells to endow the T-cell, a type of immune cell with a new property that essentially renders into a efficient cancer fighting cell.
So it’s now more then constituting marrow that have been destroyed by chemotherapy to treat the patient it itself become part of the therapy.
Exactly, and I think E.J. can comment on her technology and together, I think you will see the power of combining all of this.
Our strategy, a real problem with the cord blood is that when you transplant these patients they take very to recover, longer then marrow and the have a immune deficit for few month to a years after the transplant. So our lab been focusing on expanding the cord ex vivo to improve the neutrophil and the platelet engraftment. We have developed a number of different technologies and are now close to a promising technology were getting very rapid engraftment of neutrophil that we haven’t seen before. This is coupled with Laurence’s very promising technology, we know that lapse is a big problem in patients and we also know that brio infection in our patients is a big problem. Laurence actually is taking is receptor technology ultimately linking it with viral technology we going to be ultimately transplanting these cords that can go in and produce immune reconstitution but also target the b cell malignancies and the viruses. So it’s really an exciting strategy.
So the last question, let's talk about where this all fits in to the big picture of cancer therapy. Historically it’s been surgery, radiotherapy , and chemotherapy. This is all new, now you actually treating the cancer with the transplant. How does it all fit in?
Well I think there are a number of ways to answer that question. The simplest way is to say, as transplanters, we develop off the self therapies for patients. We want to have essentially a one stop shop. When patients malignancy they are seen at M. D. Anderson and then we for a cord from our pre-bank supply. Infuse that cord blood into patients after chemotherapy. Put that patient essentially into remission and then use that as a platform to graft in other cells. Whether it be expanded blood from E.J. or whether it be T-cells from me or other types of immune cells. So essentially this concept where we have essentially agents, biological agents cells as drugs that can be delivered on demand.
We hope within the next five years that will be a poly-pharmacy strategy. We'll have patients that are on out-units getting multiple different cellular subsets of the cord blood that are doing different things, but altogether improving the survival.
The obvious question is will this supplant the more traditional form of therapy at some point?
Cord blood is already surpassing the other types of transplantation that E.J. talked about. Cells being garnered from bone marrow or from peripheral blood so you can see that there is a lot of momentum. So it is likely this type of technology will continue to accelerate and enter into other types of therapy yet to be determined.
I don’t know that we would ever supplant… I mean we still give a preparative regiment to suppress the immune system to eradicate the tumor before we give the cord. So I don’t see the cord therapy itself replacing what we are doing but I think it’s adding improved benefit to what we are doing, and probably in tandem with what we’re doing.
Terrific! Listeners if you have questions about anything that you heard today on Cancer Newsline, please contact askMDAnderson at 1877-MDA-6789 or online at www.mdanderson.org/ask/. Thank you Dr. Shpall, thank you Dr. Cooper and for listening this episode of Cancer Newsline. Again this is a weekly series please tune in again next week for our next episode of this series. Thank You.
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