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Stem Cells For Leukemia: New Hope From Newborns

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SEATTLE, Wash. (Ivanhoe Newswire) - One person in the U.S. is diagnosed with blood cancer every four minutes. Chemo and a bone marrow transplant helps fight off the disease, but thousands of those diagnosed each year cannot find a matching donor and surviving without one is almost impossible. Now a solution may be coming from a surprising place.

From making the bed to making music, Jessie Quinn has a shadow ready to learn just about anything her mom can teach her. It was little Luna who gave her mom the motivation to fight when Jessie was diagnosed with leukemia.

"That was the first thing that went through my head actually.  It was, ah, you know, I wanted to be able to see Luna grow up," leukemia patient, Jessie Quinn, told Ivanhoe.

Doctors could not find a bone marrow match for Jessie. That's when she became patient number one in a clinical trial using cord blood stem cells from the placentas of newborn babies.

"Now we know that cord blood, which is generally thrown away as medical waste, also contains these blood forming cells," Colleen Delaney, MD, associate member at Fred Hutchinson Cancer Research Center, told Ivanhoe.

The stem cells taken from the cord blood are transplanted into the patient. Those stem cells replace the diseased blood and immune system and wage war against the cancer.

"Not only do their white blood cells come faster, but they also don't get the same side effects from the chemotherapy," Dr. Delaney said.

Most importantly, cord blood stem cells do not have to be a perfect match for the patient.

"We have a bank of these cells that can be used for any patient," Delaney explained.

Jessie is now in remission. The stem cell transplant has given her more time to teach Luna more about life.

"I was just glad there was another option," Quinn said.

Dr. Delaney is beginning a new multi-center clinical trial using cord blood stem cells for cancer patients. For enrollment information and study locations go to: http://www.clinicaltrials.gov/ct2/show/NCT01690520.

RESEARCH SUMMARY

BACKGROUND:  In 2012, there were 23,540 deaths from leukemia and 47,150 new cases in the United States.   Leukemia is cancer that starts in blood-forming tissue such as bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.  Most normal blood cells develop from cells in the bone marrow, called stem cells.  Bone marrow is the soft material in the center of most bones.  Stem cells will develop into different kinds of blood cells each with a specific job.  White blood cells fight infection.  Red blood cells carry oxygen to tissue throughout the body.  Platelets help form blood clots that control bleeding.  These cells are made from stem cells as the body needs them.  Most blood cells mature in the bone marrow.  Then they will move into the blood vessels.  When someone has leukemia, their bone marrow makes abnormal white blood cells, called leukemia cells.  (Source: www.cancer.gov)

RISK FACTORS:  The exact cause of leukemia is unknown.  Researchers do know that there are certain risk factors that increase the likelihood of developing the disease.  They include:

• Radiation:  people exposed to high levels are more likely to get acute myeloid, chronic myeloid, or acute lymphocytic leukemia. 
• Smoking:  cigarettes increase the risk of acute myeloid leukemia.
• Chemotherapy:  cancer patients treated with certain types of drugs sometimes can get acute myeloid leukemia or acute lymphocytic leukemia.
 Benzene:  exposure to benzene (found in chemicals, cigarette smoke, and gasoline) in the workplace can cause acute myeloid leukemia, chronic myeloid or acute lymphocytic leukemia. 
• Inherited Diseases:  Down syndrome, blood disorders, Human T-cell leukemia virus type 1, family history of leukemia, and other inherited diseases increase the risk of developing acute leukemia. (Source: www.cancer.gov)

TREATMENT:  Treatment will depend on the type of leukemia, the patient's age, and whether leukemia cells were found in the cerebrospinal fluid.  Treatment options can include:  watchful waiting, chemotherapy, targeted therapy, biological therapy, radiation therapy, and stem cell transplant.  Many leukemia patients use chemotherapy.  It uses drugs to destroy leukemia cells.  Patients with chronic myeloid leukemia may receive drugs called targeted therapy.  Imatinib tablets were the first targeted therapy approved for chronic myeloid leukemia, but there are now others.  Biological therapy is the treatment that improves the body's natural defenses against the disease.  Radiation therapy uses high-energy rays to kill leukemia cells.  Stem cell transplant allows the patient to be treated with high doses of drugs, radiation, or both.  After the patient receives the high dose of medications, the leukemia cells and normal blood cells in the bone marrow are destroyed.  Then the patient receives healthy stem cells through a large vein, similar to a blood transfusion.  New blood cells will develop from the transplanted stem cells.  (Source: www.cancer.gov)

NEW ADVANCES:  A different treatment option that is still in clinical trials is the use of cord blood stem cells from the placentas of newborn babies.  Umbilical cord blood, like bone marrow, is a rich source of stem cells for transplantation.  The cord blood for transplantation is collected from the umbilical cord and placenta after a baby is born.  The cells used in transplants can come from marrow, peripheral blood, and the umbilical cord blood.  The first successful cord blood stem cell transplant was done in 1988 in Paris, France on a boy with Fanconi anemia, a fatal and genetic type of anemia.  It has also been given successfully to patients with over 70 diseases, including acute lymphocytic leukemia, acute myelogenous leukemia, myelodysplastic syndromes, chronic myelogenous leukemia, juvenile chronic myelogenous leukemia, chronic lymphocytic leukemia, Hodgkin and non-Hodgkin lymphoma,   thalassemia, neuroblastoma, severe combined immune deficiency, Aldrich syndrome, and severe aplastic anemia.  The umbilical cord is routinely discarded after a baby is delivered unless the parents choose to do otherwise.  For certain patients, there are advantages to using donor cord blood stem cells instead of donor peripheral blood or donor marrow stem cells, including:  availability (cord blood is stored in a public bank, tested, and frozen); Human Leukocyte Antigen Matching does not have to be as close a match as a bone marrow or peripheral blood transplants; fewer patients get Graft-Versus-Host Disease; diversity; and less risk of obtaining an infectious disease.  (Source: www.lls.org)

INTERVIEW

Colleen Delaney, MD, Associate Member and Director at Fred Hutchinson Cancer Research Center, Cord Blood Transplant Program, talks about a possible treatment for leukemia.

Before cord blood, what was the normal treatment for leukemia?

Dr. Delaney:  Well leukemia is generally treated first by chemotherapy. There is a portion of patients who will not be cured by chemotherapy alone; they are who we are really aiming to cure by doing a bone marrow transplant. When we do that we're replacing someone's blood and immune system, which has been diseased.

You are talking about bone marrow.  That is not cord blood, right?

Dr. Delaney: When we first started doing this, it was believed that blood stem cells could only be obtained from the bone marrow.  These cells are obtained by "harvesting" someone's bone marrow. It sounds worse than it is. We basically use small needles to "grab" the blood that is contained within the bone marrow in the hip. This blood contains what we call blood stem cells and it is these blood stem cells that are what give rise to all of the cells we need in our blood system and our immune system. We now know that you can also get these same cells in the circulating blood of an individual (so called peripheral blood stem cells) for the transplant.  In addition, umbilical cord blood, the blood left in the umbilical cord/placenta after the baby is born which is generally thrown away as medical waste, also contains these very important blood forming cells.

Is there a problem because cord blood does not have a lot of cells?

Dr. Delaney:  There are some amazing pros to the use of cord blood and there are some cons. The advantage to cord blood is that it is collected at the time of delivery. The baby is born, the cord is cut, and you can just collect the blood that's in the placenta and in the umbilical cord. That blood can then be processed and stored ahead of time. It's a donor that's not going to move away; it's not going to change its mind. Thus, it is a readily available and a renewable source of cells.  We also know the immune system that is associated within that bag of cord blood is naïve. They've been protected inside the mother, allowing us to not match it as closely as we would have to match an adult immune system. For example, my immune system is an adult immune system and if I was someone's donor you would have to match very closely, but with cord blood we don't have to do that. There are about forty percent of Caucasians and a vast majority of ethnic minority, mixed race patients who can't find donors. We could find a cord blood donor for almost all of the patients who need a transplant but can't find a donor.

Why is the match so hard?

Dr. Delaney:  It relates to how incredibly diverse the human race is. Despite the fact that there are nearly twenty million people who have volunteered to be someone's donor, there are still thousands of patients who cannot identify a matched unrelated donor because we are so genetically diverse. When we match a donor to a patient, we look at specific genes that we make sure are identical in the patient and donor. For an unrelated donor we look at ten of these genes, but in cord blood we only use six and even in those six we don't have to match all six. With cord blood, even though we don't match all six, we do not see worse outcomes.

Do you have to have consent?

Dr. Delaney:  There are a lot of options women have when they're pregnant. They can pay money and have it stored at a private bank for their own future use. They can donate to a public bank or to research if the hospital they deliver at offers this or they can do nothing and the cord blood is discarded with the placenta as medical waste.

Is the fact that private umbilical cord banks are becoming more popular hurting this?

Dr. Delaney: Well, they're very successful. I mean if you have the money it's a personal choice, but I think right now cord blood is better for the general public. The chances that you will need your own are slim to none. We only recommend that someone who is pregnant store their own cord blood if they have a child or someone in their family who already has a disease that is best treated by a bone marrow transplant. They can donate it to research, which is easy if you deliver at a hospital that has a program for this. With research, you just donate your "medical waste" cord blood. We don't need to know anything about your medical history, and the donation is anonymous.  Or they can donate it to public banks if they are delivering at a hospital that accepts that. This type of donation gets added to the inventory of collected cord blood units that are frozen down for clinical use. When someone who needs a bone marrow transplant but can't find a donor. So the real disadvantage of cord blood is the amount of blood that can be collected from the placenta. For someone who's more than seventy-five pounds finding one unit of cord blood that gives them enough cells for the transplant is difficult. The small number of cells in the unit generally means that the patient will take a very long time for their blood system to come back and this makes them at risk for life threatening infections or bleeding. Now, we do transplants where we use two units of cord blood. So two different people, two different babies into one person and we know it works. However, it still takes them a very long time, almost a month for their white blood cells to come back.

So now you are trying to change that?

Dr. Delaney: Correct. That's where my research comes in. I worked in the lab with Irwin Bernstein as a fellow. He is a stem cell biologist who had discovered a certain pathway; a communication pathway within the stem cells that we think tells the stem cell to make more of themselves (or self-renew).  When I joined his lab, I decided to pursue application of his basic science findings with human stem cells to the cord blood setting. I knew that in order to make cord blood transplantation safer, we needed to overcome the problem of low cell numbers. We needed to be able to generate more blood stem cells from a unit of cord blood so that the patient who can't find a donor can get a cord transplant and have the same chances at survival. The goal from the beginning was to manipulate this pathway to generate more of these cells in the laboratory. We have done that tremendously well.

Can you double it or triple it?

Dr. Delaney: On average, every stem cell that we put in a tissue culture dish we can get 150, 200, and sometimes 400 back. In a normal cord blood transplant, we are happy if we can infuse about 150 thousand of these stem cells per kilogram of the patient's weight. When we do what I do, we have been able to achieve doses of 12 million, sometimes 40 million of these stem cells per kilogram of body weight.  And, when someone gets these cells we have grown in the lab, they don't get the same toxicity, their white blood cells come faster and they also don't get the same side effects from the chemotherapy. These cells seem to protect them from that as well

What side effects of chemotherapy and transplant?

Dr. Delaney: Mucositis is something that is like having horrible canker sores, the worst that you could possibly ever imagine to the point where it's hard to swallow. These patients will often get that, but with these cells we don't see that very much. They can eat, have less pain, and have fewer infections. This data is all preliminary because there aren't that many patients who have been treated yet, but we're about to embark on a very large multi-center trial to study this.

Greg was your first?

Dr. Delaney:  Greg actually was in the second generation of our study. In the very first study we were really looking at taking a double cord blood transplant, so two units of cord blood where we would take one of those units that had been partially matched to the patient, found specifically for that patient. We would expand the cells in the lab; give them to them fresh after they had been expanded. Logistically that's very difficult. So after we saw the success of that trial where we cut the time it takes for white blood cell recovery in half, we said let's try to make this a product that can be used for anyone anywhere. The idea here is we now take fresh cord blood units directly from the baby. The baby is born. The unit comes to us. We can expand that unit and put that in the freezer. We have a bank of these cells that can be used for any patient. We don't even tissue type them anymore. Greg was in that study to test the safety of this approach. Could we do a cord blood transplant and make these cells ahead of time and give this unit to anyone regardless of tissue typing? Because there's no immune system associated with the cells we expand in the lab, the idea was you could give it to anyone. It could be used for anyone whose white count is low, even for leukemia. So when someone is going through chemotherapy for leukemia, the idea is that I could give these cells to that patient just to protect them from infection.

How is Greg different than when he started?

Dr. Delaney: He looks amazing. You wouldn't even know he had a transplant. He has done incredibly well. A transplant is a very difficult procedure to go through for anyone. I think most adults would say they're fatigued at least for the first year. You're still on a lot of medications. You have to be very selfish and protect yourself from infections. I've been in touch with him throughout the year and he's been back at work, exercising, and living a normal life. That's what we are striving to achieve, curing people of their disease but having minimal side effects. We are still working on it, but making great strides.

Are there any downsides to the cord blood transplant and do they have to take medication for the rest of their life?

Dr. Delaney:  Just like in any blood stem transplant, I think one of our biggest enemies still is this thing called graft versus host disease. It is something that happens when foreign immune systems go into your body; most people are on some form of immune suppression for at least a  year or two. Because we're replacing their blood and their immune systems at some point, they become tolerant and at some point they come off their immune suppression. The other issue is the risk of infection as the new immune system comes in.

FOR MORE INFORMATION, PLEASE CONTACT:

Colleen Delaney, MD
Associate Member
Fred Hutchinson Cancer Research Center
(206) 667-1385
sdelaney@fhcrc.org

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