Umbilical Cord Stem Cell Donations for Cancer Patients

M. D. Anderson Cancer Center

Cancer Newsline Audio Podcast Series

Date: July 27, 2009

Duration: 0 / 17:49

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Lisa Garvin:

 

Welcome to Cancer Newsline, a weekly podcast series from the University of Texas, M.D. Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host Lisa Garvin. Today we're talking with Elizabeth Shpall, M.D.: the Asheville Smith Professor of Medicine in the Department of Stem Cell Transplantation and Cellular Therapy. Welcome Dr. Shpall.

 

Elizabeth Shpall, M.D.:

 

Welcome, thank you. Thank you for having me.

 

Garvin:

 

Today we're going to be talking about cord blood which has become an important source for transplant material at M.D. Anderson and hospitals around the world. First of all Dr. Shpall, tell us where is cord blood derived?

 

Elizabet Shpall, M.D.:

 

So cord blood is derived from the placenta of infants that are being born. It's the sack that surrounds the baby in the mother's uterus that has lots of blood vessels in it and feeds the baby through the nine months of pregnancy. And when the baby is born, the placenta is delivered and in that placenta are veins that are full of stem cells. We simply stick a needle into that placenta after the baby is safely born and out of the mother's uterus. We can either stick a needle into the placenta while the uterus still has the placenta in it or we deliver the placenta into a bucket and can collect the blood that way. But we simply stick a needle and drain about a milk bottle full of blood which is extremely rich in the stem cells that we need for transplantation. We take that blood in standard blood bags to the laboratory here at M.D. Anderson where we freeze it and have it for future use for stem cell transplantations. Before we freeze it, we take out samples for infection, for an HLA typing which is the typing on everyone's cells that we have to match when we do a transplant. So we take out samples for lots of different tests including infectious disease testing and typing of the HLA which is the human leukocyte antigen which everyone has on their surface of their cells. And it is that HLA that we must match when we do a transplant. Once the cord is frozen, all of that information is gathered. All of the results are gathered and put into a big database, and if the cord meets the specifications that are acceptable for transplantation that have to do with a large enough size, lack of any infection, and all of the appropriate testing shows normal results, then that cord is put into a registry. And with all of the information associated with it and when a patient needs a transplant, they actually submit their HLA type to the registry and if the cord matches that HLA type, it comes up in a report that goes to the transplant doctors. And the transplant doctors then know that they can have that cord for transplantation if the patient needs it.

 

Garvin:

 

So M.D. Anderson does have a cord blood bank and it's one of the few in the country right now, is that correct?

 

Shpall:

 

Right, well there are about probably 30 cord blood banks in the United States now: approximately 8 or so large cord banks. And we're one of the largest. The largest bank is in New York. There's another one in North Carolina at Duke. St. Louis has a cord bank and there are many around the country. But ours is one of the largest and we're getting larger. And we've collected about 16 thousand cord blood units. We've banked about half of those. The others were not big enough or had others problems with them. So we have almost 8 thousand units in our cord blood bank and we have as of this morning transplanted -- we have released them for transplant to our 191st patient this morning.

 

Garvin:

 

Wow.

 

Shpall:

 

And these were for the most part patients either here at M.D. Anderson or in Texas and even beyond. We've released units to India and China and all over the world but for the most of them in the United States. These were for the most part patients who had no other good transplant options and therefore you know likely a very critical therapy for them.

 

Lisa Garvin:

 

Are there still challenges to you know collecting cord blood? Probably it's something that maybe mothers need to be educated about that it's safe for them and safe for their new baby. But also too I wonder if the stigma of stem cells is still kind of affecting cord blood donations?

 

Shpall:

 

Very good question! The answer is yes. We are collecting cord blood now at 5 different hospitals in Houston. And when we started in April of 2005 about 30 percent of mothers refused to donate for the very reasons that you stated: worried about cloning and stem cells. And what we have learned over the years is that education of the mothers and the families is critically important. And so we have an extensive teaching brochure. We have fully trained collectors who educate the mothers and explain the details of cord blood transplantation. And with that education which the mothers can get either in their prenatal classes or when they come to the hospital for delivery, the acceptance rate has actually gone way up. And now only about 6 to 7 percent of mothers refuse to donate. So we've made a major inroad into that problem.

 

Garvin:

 

In just a very short time. That's great.

 

Shpall:

 

Yes, yes, yes.

 

Garvin:

 

And all it is -- tell us about the process of donating the cord blood. I guess they have to sign consent forms and so forth. Kind of walk us through what a mother would do.

 

Shpall:

 

Sure. So the mother has to be at least 34 weeks gestation - delivering at 34 weeks or beyond - to be eligible to donate. She is given a brochure and a consent form which describes the fact that the cord will be collected, that her blood and her baby's blood will be tested for a number of infectious diseases including HIV, that we will look in her chart to make sure that there is no medical contraindication to collecting the cord. And all of those things she has to agree with up front which as I said they typically do. They sign the consent form, understand completely how the process will take place and then we wait. And when she goes into labor and the baby is born, we have collectors at all of our hospitals. And so either the collection can be done in utero as I said. The baby is born. The placenta is still in the uterus. And the obstetrician with the help of our team sterilizes the cord and sticks a little needle in and drains the blood. Or the placenta is delivered into a bucket. We have a room on each of the hospital units where we are collecting. And in that room they hang the placenta up on a stand and again stick a needle and drain a milk bottle full of blood into a blood bag. It's all labeled and bar coded and then we store it for several hours and have delivery people come and pick up the cords and bring them to M.D. Anderson where they are checked in, processed, the sample's taken for all of the testing that needs to be done, and then they are frozen. We need to have the cord bloods frozen within 48 hours of collection in order to make it to the bank to be clinically useable because we know beyond that, they're not as good.

 

Garvin:

 

Let's walk through what stem cells do. I think in a nutshell I can say - not being the expert - that stem cells are like very early developmental cells that really can be anything. I mean we start with stem cells and then differentiate and become different organs.

 

Shpall:

 

Right so what we use for our patients are hematopoietic stem cells: are bone marrow derived stem cells. And what these particular stem cells do is the major functions of these stem cells are to make platelets to keep patients from bleeding, to make white cells to keep one from getting infected or to fight infection, and red cells to carry oxygen. So we have many patients who have diseased marrows either from cancer, you know leukemia, lymphoma or from hematologic diseases, inborn in metabolism, or even more recently sickle cell. And with diseased marrow the patients won't live very long or very healthfully. So for many of these diseases, the treatment of choice is a stem cell transplant. And what that means is that the patients get -- come into the hospital and they get treated with chemotherapy or a chemo radiation program that will kill the diseased marrow. And then we infuse a healthy marrow product from proliferate blood or a bone marrow or a cord blood. And those healthy cells know where to go and they hone into the bones and begin to grow. And in a matter of 2 to 4 weeks, they begin to produce the white cells to fight infection, the red cells to carry oxygen and the platelets to keep the patient from bleeding. During that timeframe, before the stem cells take, the patients are in very protected rooms with you know filtration to keep out infection. They're on a lot of antibiotics. They're getting blood and platelet transfusions. And it's that time period that is the most fraught with complications in terms of getting the stem cells to work. But once they start working and functioning, then the patients are much less likely to be infected and much less likely to need transfusions. So the first major obstacle to therapy with stem cell transplantation is overcome. As a stem cell transplant physician, the first choice for a donor for our patients with marrow diseases is a family member. And we have to match the donor with the patient in terms of what we call the HLA: human leukocyte antigens. Those are makers that everybody has on their cells. You get half from mom: half from dad. And what we like is to have a perfect match in 10 of 10 or actually 14 out of 14 of those markers: 7 from mom, 7 from dad. The perfect match is the safest and best transplant. Unfortunately, patients only have a 1 in 4 chance of having a family member who will be a perfect match for them. And so 3 out of 4 patients will not have a match and therefore over the past 2 decades we have increasingly been using unrelated donors.

 

Garvin:

 

Or matched unrelated donors. Also called MUD.

 

Shpall:

 

Matched unrelated right, matched unrelated donors called MUD. We have the National Marrow Donor Program Registry. We have 7 million donors and these are matched, unrelated donors that provide the stem cells to our patients. If a patient is Caucasian of Western European origin, then they can often find a donor in the registry. However, if you are a patient from an ethnic minority be it African-American, Hispanic, Asian, Jewish, we often never find donors in the registry for a number of reasons. The minorities appear to be underrepresented in the registry. In addition - particularly for the African-American population - the HLA typing is more heterogenous. It's a more complicated gene pool. It's harder to match. And so for these reasons, cord blood has exploded on the scene as a marvelous alternative for stem cell transplantation to patients who don't have a donor in the registry. Why is that? Number 1: because the cord blood is a more naive cell. It's a younger cell. And it has much fewer -- it's a smaller stem cell graph and it has fewer T-cells in it. It appears to cause less complications - the major complication being graft-versus-host disease - even though it can be used in a more mismatched situation. So where we routinely want to have a perfect match - a 10 out of 10 or a 6 out of 6 of the basic matches for marrow and blood - we are routinely using a 4 out of 6 match in cord. The vast majority of patients transplanted in the world to date - more than 15 thousand - have had 4 out of 6 matches and they appear to produce you know comparable results with maybe even less graft-versus-host disease than a completely matched marrow. So that is one reason why the inventory of cord blood in the world is much smaller than prolifera blood, but we're still allowed -- we're still able to find the donors because you just don't have to have as many to find a 4 out of 6 match.

 

Garvin:

 

Do you think that other countries could step up to the plate and maybe there'd be like a global cord blood awareness program? It sounds like that if you did that the resources would be almost limitless.

 

Shpall:

 

Well, it is already happened. In fact, cord blood is a global industry. The biggest cord banks in the world outside New York are in Dusseldorf, Milano, Barcelona and 1 growing in 3 different regions of France. We often get cord bloods from around the world. The Cord Blood Registry: the National Marrow Donor Program lists all the cords and it is a hugely international activity that is ongoing now. Of the patients transplanted in Houston in our transplant unit, one-third came from outside the country. One-third of the cords have come from Spain or many from Germany, Australia and we similarly have sent our cords all over the world as I said originally. So it is a very global industry right now and the countries around the world are stepping up. There's now new cord banks all over China: many. In Japan, there are 9. In Israel, there are 2. And so it's really a hugely exciting and internationally supportive activity because of our patients all over the country and all over the world who can benefit from the rest of the world's units.

 

Garvin:

 

Now has the pendulum swung from bone marrow to cord blood? I mean what is the percentage being done cord blood versus bone marrow transplants?

 

Shpall:

 

Our first choice for transplant is still always a 10 out of 10 matched, unrelated donor. Those are being done more frequently than cord blood. But for patients who don't have that perfect 10 out of 10 or who don't have time for example patients with acute leukemia, often need a very quick transplant because they're only going to be in remission for a few weeks. And in that setting it takes longer to get a donor than it takes to get a cord blood which is frozen and can be shipped overnight. So the number of cords is definitely increasing going up every year - but it hasn't surpassed the unrelated donors. And you know, it probably never will but it is providing an increasing number of transplants and making more patients able to get a transplant than ever before.

 

Garvin:

 

And faster too!

 

Shpall:

 

And faster! Definitely faster!

 

Garvin:

 

Well great. Thank you very much. Do you have any final thoughts you'd like to leave with the audience before we go?

 

Shpall:

 

I think it's an exciting time to be in stem cell transplantation. Cord blood has allowed us to treat patients, particularly those minority patients who have no other options and we didn't have time to talk much today about what we're doing in the laboratory to make cord blood safer, but it does take longer to engraft, to recover, to take than a bone marrow, and as I told you, those during that period there's an increased risk of infection and bleeding. And so we have major projects in our laboratory trying to grow the cords ex-vivo - outside the body, in the laboratory for 2 weeks and then infusing them. And we're seeing very exciting results with more rapid engraftment in the patients who get these expanded cord blood units compared to the old days when we were not able to do that. And so that is very gratifying to see that we can -- even though it's not perfect, we're getting better and better at making it safer for the patients.

 

Garvin:

 

Great, thank you very much for being with us today. If you have questions about anything you've heard today on Cancer Newsline, contact Ask M.D. Anderson at 1-877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.

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