Final Write Up

Topic: Adult Stem Cell Application

Research Question: How are adult haematopoietic stem cells used to treat leukemia patients?

Problem/Cause

To start with, leukemia or the cancer of blood and bone marrow has couple of rare leukemia types but the most common are chronic and acute leukemia. Acute leukemia causes patients, produce or develop leukocytes (white blood cells) abnormally. The body produces a large number of abnormal white blood cells which looked like blasts or immature cells. As white blood cells are produced and can be found in the bone marrow of a person, the abnormal cells gather itself in the bone marrow and this then affects the number of normal white blood cells being produced. In other words, these causes the abnormal cells to dominate the number of normal white blood cells produced in the bone marrow. They can't carry out their normal work, and with that they multiply rapidly, so the disease requires an aggressive yet timely treatment. It is quite different with chronic leukemia where it involves mature blood cells as they replicate and accumulate slowly and would work for a period of time. Therefore, in some forms of chronic leukemia, it could initially go unnoticed or undiagnosed for years. Leukemia itself has been thought to occur when some blood cells acquire mutations in the DNA where the instructions to where and how a cell acts are held.  This reason was thought to cause the cell to grow and divide more rapidly and to continue living when normal cells would die. Over time, these abnormal cells can crowd out healthy blood cells in the bone marrow, leading to fewer healthy blood cells and causing the signs and symptoms of leukemia. The specific cause of leukemia is still a mystery although experts have strongly suspected and are speculating that artificial ionizing radiation, genetic predisposition where studies have shown that people have a risk of developing leukemia because of a single or multiple genes, viruses such as HTLV-1 (human T-lymphotropic virus) and HIV (human immunodeficiency virus) and lastly people with down syndrome have a significantly higher risk of developing leukemia. Experts believe that people with certain chromosomal abnormality may have a higher risk than people who don’t. These are however still in research and the main cause or the most specific cause is still unknown to date.

Samples of blood from a healthy person and one with leukemia, showing an increase in the numbers of white blood cells.
Picture from: "What Is the Difference Between Red and White Blood Cells?" WiseGEEK. N.p., n.d. Web. 25 Oct. 2014. <http://www.wisegeek.org/what-is-the-difference-between-red-and-white-blood-cells.htm>.
Key Words: Erythrocytes=Red Blood Cell, Neutrophils= A type of white blood cell, 
found in blood stream extremely mobile as they are recruited to site of injury within trauma, 
Lymphocyte= Another type of white blood cell and extremely fundamental as they are decisive 
to what the immune system response against diseases, Monocyte= Another 
type of white blood cell, fundamental to the process, holding multiple roles and are the largest of all.
Platelets= Blood cells that has a main job to stop bleeding

Effects
Leukemia patients usually has symptoms such as fever or chills, fatigue, frequent and sever infections, losing weight, easy bleeding or bruising, swollen lymph and enlarged liver or spleen, tiny red spots in skin, bone pain and excessive sweating. In other words, leukemia patients are really suffering from this deadly disease not only physically but mentally. They might suffer depression, fear, lost of hope etc. In addition to this, leukemia patients or cancer patients in general has a significantly higher chance of dying than people who don't.

Estimated Deaths of Leukemia Cases in US for 2014
Picture From: "Disease Information & Support." Facts and Statistics  | The Leukemia & Lymphoma Society. N.p., n.d. Web. 25 Oct. 2014. <http://www.lls.org/diseaseinformation/getinformationsupport/factsstatistics/>.

In this table graph, we can see that the numbers of people affected by leukemia will increase in 2014. But this is a very serious matter as this is only in the U.S. while worldwide, leukemia is the cause of 265,000 people worldwide in (2012) due to leukemia according to http://www.cancerresearchuk.org/cancer-info/cancerstats/cancerstats-explained/stats-terminology-and-calculations/#Data, and are still increasing each year.

Solution to Leukemia:
Treatment options for leukemia might vary as they depend on the type of leukemia and many individual things about the patients. Treatment might include chemotherapy, steroid or a more intensive procedure such as high-dose chemotherapy combined with adult haematopoietic stem cell transplant.

To be able to know these procedure we need to know more about adult stem cells and what it does. Adult stem cells are undifferentiated cells  that are found in small amounts in adult tissues of a child or adults. It was thought to only be able to produce or renew cells with alike or similar type of cell. For example, stem cells in the bone marrow can only produce blood cells. Stem cells are known to posses the ability to repair and replenish damage tissues and reproduce cells that are dying. However, in recent years scientist has found out that adult stem cells can produce cells unrelated and different from the stem cell type. Basically, adult stem cells posses the ability to transform or produce specialized cells if needed to and this means that adult stem cells can produce or divided itself to produce daughter cells that can either have a similar cell type or cells that have a more specific function/specialized cells. However, scientist are still debating and researching regarding this matter.

The most effective known method to treat leukemia patients is by using high dose of chemotherapy combined with a haematopoietic stem cell transplant. Haematopoietic stem cells are known to produce blood cells such as white blood cells and red blood cells. They can be found in a person's bone marrow, peripheral blood and the umbilical cord. High dose chemotherapy is the most effective way to kill leukemic cells but by using chemotherapy, normal healthy blood cells will be destroyed in the bone marrow. This is where haematopoietic stem cells are used by doctors to replenish/exchange the damaged blood cells with new ones. When the stem cell is transplanted into the patient, the stem cells will start producing new healthy daughter cells and therefore replenish the damaged blood cells. These stem cells can be collected from either the patient's own bone marrow but only if they can collect enough amount of healthy stem cells or they can gather healthy stem cells from a donor.

The video explains the types of bone marrow/stem cells transplants that can be used to treat leukemia patients.
Video link: https://www.youtube.com/watch?v=YuirlplSfBU

Diagram of Haematopoietic stem cells in the bone marrow and its ability to transform into different specialized cells
Picture from:"Blood Cell Formation from Differentiation of Hematopoietic Stem Cells in Red Bone Marrow." Blood Cell Formation From Differentiation Of Hematopoietic Stem Cells In Red Bone Marrow. Stock Photo 186712559 : Shutterstock. N.p., n.d. Web. 25 Oct. 2014. <http://www.shutterstock.com/pic-186712559.html>.

Transplant Procedure:

Haematopoietic stem cells can be found in the bone marrow and the peripheral blood and therefore doctors are also able to do either bone marrow transplant or the peripheral blood transplantation. The procedure itself can be done in three different types of bone marrow and peripheral blood transplantation, the first is autologous transplant (using the patients own stem cells), syngeneic transplant (Patients will get identical twin's stem cells if possible) and lastly patients get stem cells from donor (allogenic transplant).

The first procedure that can be used is by collecting the haematopoietic stem cells from the bone marrow in a process called 'harvesting' or by gathering stem cells from the liquid part in the center of the bone marrow. The doctors will use anesthesia and inject needles over the hip boneor breast bone and harvest the marrow. Then, the next process is removing the blood and bone pieces from the marrow to finally keep it frozen in a technique called "cryopreservation". It will then be kept frozen until it will be used for transplantation.

Another procedure that can be used to harvest haematopoietic stem cells are by collecting it from a donor's bloodstream in a method called "apheresis or leukapheresis". In order to do this procedure, the donor is prepared by giving them a medication that will increase the number or production of healthy haematopoietic stem cells in their body. Once this preparation process is finished, doctors will start by taking the blood from the vein in the arm by using a needle. The blood gathered will then be processed in a apheresis machine which is a blood cell separator machine. The stem cells and healthy blood cells are collected but doctors will only harvest the stem cells while other blood cells such as platelets, red blood cell, etc. will be transferred back to the donor using catheter. Doctors will then freeze the stem cells for when it is needed for transplantation.

The next procedure that are a procedure that requires a donation from a family in which it requires an umbilical cord from a baby to harvest haematopoietic stem cells. This process can be done by collecting the blood from the umbilical cord attached to the baby when its being given birth. It will then be frozen for transplantation uses like the other methods of collecting haematopoietic stem cells. These haematopoietic stem cells collected from the umbilical cord can be used for both child and adult patients although it is more commonly used for child patients. The reason being is that the stem cells found in the umbilical cord is limited and therefore with the reason of a child being smaller than an adult, child patients usually only require one umbilical cord as the cord blood would contain sufficient blood for the child patients which is not the cases for adult patients where they usually require one or more umbilical cords.

The transplantation will start when all preparations are ready and the doctors are sure with the amount of stem cells collected or are sure with the matching of patient's blood type with blood samples of the donor in a test called human leukocyte antigens (HLA) test. By undergoing this test, it will make sure the patient's immune system will not reject the transplant. It is also important to note that the patients have undergo a series of radiation therapy. Then, much like blood transfusion, the patient will receive the stem cells intravenously and this procedure will take about an hour. Right after entering the blood stream, ideally the stem cells will travel to the bone marrow and will start making new cells in a procces known as engraftment. The team will monitor the blood counts for months and during this period, the patients may need to give red blood cells and platelets transfusions. The doctor may give patients drugs or antibiotics to prevent infections and the graft-versus-host-disease (GVHD) condition.

The video explains about the bone marrow transplantation and procedures used to get stem cells from a donor.
Video Link:https://www.youtube.com/watch?v=PlFhC1egESI

The Apheresis machine used to separate stem cells with other blood cells in the stem cell harvest
Picture From:"Apheresis Machine ACP®215 HAEMONETICS." Apheresis Machine. N.p., n.d. Web. 26 Oct. 2014. <http://www.medicalexpo.com/prod/haemonetics/apheresis-machines-78504-482188.html>.

Benefits:

There are so many benefits of using haematopoietic stem cells as they are so beneficial for leukemia patients. By using the haematopoietic stem cells transplant, the survival rate of a leukemia patient increases drastically. This reason is valid as we know that by using high-dose of chemotherapy, serious effects can be caused. Even though, higher doses of chemotherapy might be more effective to kill leukemic cells but they could severly damage the bone marrow and this could result into a very life-threatening condition. By using the haematopoietic stem cells transplant, will allow doctors to use an even higher dose of chemotherapy and this could lead into a more effective way to treat leukemia patients as after the treatment is finished they will receive the stem cell transplant which will restore and replenish the damaged blood cells.
Another benefit that we can see is that mentally, the patients will be mentally stronger as this transplant will give them hope of surviving. This can be seen as the last chance of survival according to Dr Laughlin, a Professor of Medicine in Case Western Reserve University School of Medicine "Even with a cord blood transplant these patients often suffer from life-threatening infections. But the fact is, without attempting this innovative therapy, none of them would survive."

Limitations:

Every thing has both sides into them and so does this haematopoietic stem cell transplant. With many benefits into them there is also limitations to the method. Firstly, patients that has undergoes bone marrow transplant is very vulnerable to infections as the transplanted stem cells needs time to start producing healthy blood cells. These stages are very critical for the survival of the patient as infections can occur due to the inevitable delay in replenishment of the patient's immune system with the white blood cells. Careful observation and treatment using antibiotics can help reduce chances of infections.

Another limitation to using haematopoietic stem cell transplant is that another life-threatening effect is the Graft-versus-Host disease (GvHD) where complication will occur when the donor blood cells attack the vulnerable patients body. It will cause a serious complication and can be very life-threatening to the patient. This can of course be minimized by the HLA test which is the matchmaking of the patients blood type and the blood sample of the donor. The other strategy to prevent and anticipate the GvHD is by suppressing the immune system with drugs and removing a type of white blood cell (lymphocytes) from the transplant.

Factors that might affect the Success of Solution

The first factor that might affect the success of the solution is the economical factor that takes place. This can be proved as according to cancer.org, stem cell transplant can cost well over 100,000 dollars which can still add up in certain conditions as by doing the transplant, it would mean long hospital stay to monitor the patients and how the blood cells have developed. Insurance may not even pay for all types of transplant which would leave patients in a predicament as they will be left with hospital bills even though they needed this procedure. Another thing is that even when the insurance does cover the transplant, other needs will probably cost around ten thousand dollars and this is why many patients reconsider this method as the survival rate isn't that big due to different reasons and they also think about the burden they will leave the family with when he/she recovers. Money spent towards the transplant is therefore no guarantee of success and will therefore affect the economical side of things for the families as the procedure is pricey and therefore arise the economical issue.

The other issue that arise regarding the use of haematopoietic stem cells is the social issues surrounding them. With the use of adult stem cells transplant, leukemia cancer patients can now be treated and so this affects people in the social community. This will therefore affect the patients as it brings hope to the patients and as the last chance or the last string of hope knowing that there will be an increase in survival chances of the patients. Today, according to who.int, "around 50.000 transplants are carried out annually worldwide and they are increasing each year." and "Stem cell transplantation also remains the last hope for patients with advanced or refractory disease". This affects the common society as leukemia patients are being treated and more of them are actually surviving.

But even so, another social issue that will affect the success of the solution. It is related to the number of donors that are willing to donate their stem cells for needing patients. The number of these donors are very limited and could not sustain the number of request by cancer patients. It is a very relate able thing with our society today as it is a social issue that affects the community as a whole. It is well known that doctors need to find the matching and perfectly matched blood type of patient and the blood samples of the donor to basically try and avoid the Graft-versus-host disease (GvHD). In fact, it is very important as with a very limited donor supply and an increasing demand for donors, the real challenge is to find a perfectly matching blood type as the chance of getting a required blood type and characteristics are decreasing. This is just an example of how our society today has a problem to be willing to sacrifice and help people in need. This is a factor that could and will affect the success of the transplant itself as the chance of having a complication and getting the GvHD decreases if there are more donors which will result in an increasingly higher chance of having a perfectly matched blood tissue and type.

Bibliography:

Book Sources:

-Humber, James M., and Robert F. Almeder. Stem Cell Research. Biomedical Ethics Reviews. N.p.: Springer, 2004. Print.

-Frederic P. Miller, Agnes F. Vandome, John Mcbrewster. Adult Stem Cell. S.l.: Vdm Pub. House, 2009. Print.

-Snow, Nancy E. Stem Cell Research: New Frontiers in Science and Ethics. Notre Dame, IN: U of Notre Dame, 2003. Print.

Internet Sources:

-The Editors of Encyclopædia Britannica. "Lymphocyte (blood Cell)."Encyclopedia Britannica Online. Encyclopedia Britannica, n.d. Web. 25 Oct. 2014.

-"Neutrophil: Low Neutrophil (Neutropenia) & High Neutrophil Counts - Medfriendly.com." Neutrophil: Low Neutrophil (Neutropenia) & High Neutrophil Counts - Medfriendly.com. N.p., n.d. Web. 25 Oct. 2014.

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-"What Is Leukemia? What Causes Leukemia?" Medical News Today. MediLexicon International, n.d. Web. 24 Oct. 2014.
-"Leukemia Patients Survive With Stem Cell Transplant." ScienceDaily. ScienceDaily, n.d. Web. 26 Oct. 2014.
-"Stem Cell Transplant for Acute Myeloid Leukemia." Stem Cell Transplant for Acute Myeloid Leukemia. N.p., n.d. Web. 26 Oct. 2014.
-"Leukaemia: How Can Stem Cells Help?" EuroStemCell. N.p., n.d. Web. 23 Oct. 2014.
-"Bone Marrow Transplant." John Hopkins Medicine. John Hopkins, n.d. Web.
-"Stem Cell Transplant for Acute Lymphocytic Leukemia." Stem Cell Transplant for Acute Lymphocytic Leukemia. N.p., n.d. Web. 26 Oct. 2014.
"Haematopoietic Stem Cell Transplantation HSCtx." WHO. N.p., n.d. Web. 26 Oct. 2014.