How To Treat Leukaemia With Cord Blood Stem Cell
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1 Cord blood for the treatment of acute lymphoblastic leukemia in young children By Caitlin McGreevy Kiara Paramjothy Pass with Merit RESEARCH PAPER BASED ON PATHOLOGY LECTURES AT MEDLINK
2 Abstract: Stem cells are a medical breakthrough. Research has been ongoing in the field of cord blood stem cells being used for the treatment of various blood diseases. This paper will explore the possibilities of the treatment of acute lymphoblastic leukemia in young children with their own cord blood stem cells, in particular looking at two successful cases with autologous infusions of stem cells. We will conduct a Gedanken experiment by using what we have learnt about this type of treatment and the possibility of it being used to treat adults with leukemia. Introduction: Stem cells are becoming more useful in medicine, as they are so versatile and can be used to treat a variety of diseases. The majority of stem cells are cells that are pluripotent, meaning they are greatly unspecialized and have the potential to become many different types of cells. There are three main types of stem cells: embryonic, adult and umbilical. Embryonic stem cells are extracted from an embryo and have different levels of specialisation depending on the age of the embryo. They start off totipotent (they can form any of the approximately 210 cell types in the body), and then at the 8 cell stage they become pluripotent (in which they are slightly less specialised). A stem cell has all of its genes activated meaning it has the potential to be anything. As it becomes more specialised, some of the genes start to deactivate, this continues to happen until the genes that are left active in the cell are correct for its purpose and are producing the right proteins, as one gene codes for one protein. For example, a pancreatic cell will leave the gene for producing the hormone insulin activated, unlike a heart cell that does not require insulin to be produced. Differentiation is the term used when describing a cell becoming more specialised for a purpose. As an adult, nearly all of your cells will be differentiated and specialised. In some organs, there are adult stem cells among the specialised cells that are able to become most of the tissues inside that organ not any organ. For example bone marrow produces blood, and in the bone marrow there are stem cells that are able to become most types of blood cell. Adult stem cells are a lot less common than embryonic, they are harder to attain and are more specialised so have less potential. However using adult stem cells avoids the ethical issues surrounding embryonic stem cells and with adult stem cells there is the advantage of using your own cells and therefore preventing rejection and having to use immunosuppressant drugs. Ethical issues of embryonic stem cells: Science faces controversy over the use of embryos for stem cells, as there are many mixed opinions among the public. The main issue is that many people believe that life begins at conception therefore an embryo has human rights, and using the embryo for stem cell research is a violation of these. Many religions share the belief that God decides what happens to you; therefore by trying to cure diseases we are not only messing with God s will, but also doing so in an unethical way. 2
3 However, there are a few faiths, such as the Jewish faith, that have different beliefs about an embryo s rights. The Jewish faith teaches that the embryo does not have human rights until later on in the pregnancy; therefore embryonic stem cell research is acceptable. Because of this, many stem cell researchers are moving to countries of the Jewish faith to carry out their research. Because of the ethics of stem cell research on embryos, the rules are strongly enforced. In the UK the organisation called the Human Fertilisation and Embryology Authority (HFEA) have different licenses on who can do what regarding stem cell research. For example a scientist could be granted a license for bringing about the creation of embryos in vitro, and keeping or using embryos for the purposes of a project of research. 1 If people do not abide by the rules of their license then they can be taken to court. This paper will focus on stem cells from cord blood, which has a number of benefits and is becoming increasingly popular. It involves taking a sample of the umbilical cord/placenta of a newborn and storing the pluripotent cells in a bank for any future needs. There are two kinds of banks private and public. Private banks are the banks not associated with the NHS and the kind that store your cells privately so that only you or your close relatives can use them. It is expensive to do so and is not backed by the NHS they don t completely agree with it. For example, cord blood stored with Cells4Life can cost around 2,000, and only lasts for 25 years. The NHS Cord Blood Bank Scheme is a free service designed to get people to voluntarily donate their child s cord blood cells to be used by patients in order to treat them. The NHS sees the potential of the use of stem cells from cord blood for the treatment of diseases. It s a free scheme designed to attain more stem cells that can used to save peoples lives. Benefits of cord blood over other stem cells Cord blood eliminates the controversy in the ethics of the research. No life is sacrificed and there is no harm in everyone doing it. The umbilical cord and placenta is usually thrown away so it seems viable to keep useful cells for future use. It requires consent from the donor (parents of the donor) but it will not harm them in any way. Another benefit is that there are no debates in whether a life is being ended for the purposes of the research, as the cells in the umbilical cord will never develop into a human. They are also pluripotent, highly unspecialised. Human stem cells are more specialised than embryonic and cord blood stem cells, and cord blood stem cells eliminate ethical concerns and are highly unspecialised, however some embryonic stem cells, depending on the stage, are more unspecialised. When treating leukaemia, bone marrow transplants are common, however, as the bone marrow is not their own, the patient body may reject and cause an 1 3
4 immune response, which can make the patient very ill. Recipients are usually required to take immunosuppressant drugs regularly, which can be an inconvenience and lower the efficiency of their immune system making them more susceptible to infections that lead to viruses. If the patient were to receive cord blood stem cells, then a rejection is much less likely to happen because the cells have not yet developed the features that can be recognised and attacked by the recipient s immune system. Also, because umbilical cord lacks welldeveloped immune cells, there is less chance that the transplanted cells will attack the recipient s body, a problem called graft versus host disease. 2 The problem we are addressing in this paper is the treatment of leukaemia and how effective it is. Cord blood looks promising as a possible treatment that avoids problems of the current treatment of people with acute lymphoblastic leukaemia. Figure 1 shows how a cord blood stem cell called a hemocytoblast becomes specialised in the patient s body, replacing the abnormal cancerous leukocytes that would have been destroyed during chemotherapy with a new healthy replacement. Leukocytes are labelled in the diagram. Figure
5 Discussion: Cord blood is becoming a popular topic of research for scientists, because of the promising aspects discussed in the introduction. For leukemia, although there hasn t been large scale clinical trials into using cord blood as a treatment, there have been some case studies into patients who have chosen to use their own, or a close relative s cord blood as a treatment. One case study, carried out by Ammar Hayani et al, has been given the title of First Report of Autologous Cord Blood Transplantation in the Treatment of a Child with Leukemia, and is of a 3-year-old girl who had acute lymphoblastic leukemia. After relapsing once, and then going into a second remission, she received a cord blood transfusion of her own blood which had been saved since her birth, as well as chemotherapy and radiation therapy. 20 months after the transfusion she was in complete remission. This case study supports the use of autologous cord blood transfusions, because as well as the patient achieving complete remission, the paper mentions no signs of rejections or adverse side effects. This implies that cord blood does have the advantage over normal blood transfusions of avoiding rejection, and not requiring the use of immunosuppressant drugs. However, there are things that should be taken into account when using case studies like this. Firstly, a case study usually studies one person, which does not give representative results, and therefore the results cannot be generalised for the population. Also, as she was already in remission, and the cord blood was only added to the treatment she was already receiving, it cannot be assumed that the cord blood was the only reason she did not relapse again. In the American Cancer Society's most recent estimates for acute lymphoblastic leukaemia cancers in the United States for 2012, it is stated that there will be 6,050 new cases of acute lymphoblastic leukaemia and about 1 out of 3 will be in adults. 3 Often, people associate leukaemia with children, however from these estimates it is evident that adults also suffer from leukaemia. Finding research into treating adult leukaemia with autologous cord blood is difficult because storing cord blood is a recent idea, therefore only children have been able to benefit from their own cord blood. In our Gedanken experiment our aim would be to study the efficacy of the use of autologous cord blood in the treatment of adult acute lymphoblastic leukaemia. Unlike the case study of the child mentioned above, we would conduct this experiment on a larger scale, aiming to find at least 20 willing volunteers with the illness. The control group would be the current patients of adult acute lymphoblastic leukaemia receiving the regular dose of treatment e.g. chemotherapy and radiotherapy. The patients taking part would have to be in the same stage of the illness, for example they had all had the illness for the same length of time and their condition had not been declared terminal. It would hopeful to have equal amounts of women and men of a similar age. If the results are promising and 3 5
6 show signs of improvement, they may give a reason to investigate further. Therefore we would then go on to repeat this experiment on adults of different ages and different stages of the illness to get a broader understanding of the treatment on adults with acute lymphoblastic leukaemia. This transfusion can only be given once as the amount of autologous cord blood stem cells is small, so any effects would be dependent on that one transfusion. It could be useful to research into tissue culture of cord blood, to give the ability to produce than the small amount extracted at birth. Once a week for 6 months following the transfusion, a blood sample will be taken and a lymphoblast count would be carried out. We would be expecting that the lymphoblast count would decrease if the transfusion was to have the desired results of being a successful treatment. During the 6 months each patient would receive the same alternative treatments e.g. chemotherapy and radiotherapy, as they would if were not part of this trial. This is mainly for ethical reasons on the patients behalf; as if the cord blood treatment were to be unsuccessful the other forms that are known to work would not be hindered. Another reason is that the results will be compared to the control group. The people undergoing the trial will be halved in to two groups, those receiving their own cord blood and those receiving a placebo the control group will just be given a normal blood transfusion with their own blood type. The nature of this trial is therefore blind, the patient does not know if they are receiving the treatment, however it would be logistically very difficult for the doctor to be unaware. Many ethical concerns are eliminated in this trial due to the fact that our treatment does not involve the use of embryonic stem cells or destroying any form of life. As autologous cord blood has been used successfully on humans before without serious side effects, this indicates that the patients taking the trial should not be under any serious harm, and rejection to their own cells is highly unlikely. The patient would have to give informed consent for us to have the right to treat them; this means the patient would know exactly what was going to happen to them before giving their consent to take part. They will also have knowledge of the potential outcomes of the trial, and particularly that the treatment may not have much success. Recipients will be made aware that there is an exactly 50% chance of them receiving their cord blood, and 50% chance they will receive a placebo, and they must ensure they are okay with that. They must be told that by taking part in this trial their storage of cord blood would be used up and so not available in the future. 6
7 Our results would be recorded in a table each week; here is an example of what part of the table would look like: Lymphoblast count Patient number Week 1 Week 2 Week 3 Week Mean Average Conclusion There are evident problems with our trial. As we are studying on adults, it could not take place until the far future when adults begin to have their autologous cord blood stored. Therefore any progress will be limited and people may want to put their time and money into research they can carry out and use now. Another issue could be finding willing volunteers, as although the risks associated with it are very low, we have no guarantee they will receive any benefits from this treatment. The disease is less common in adults, making it even harder to find patients. The patients would already be under pain from the illness and the regular treatments, and this would be adding to it, with the initial transfusion and then the 6 month follow up of weekly blood tests. This is an ethical issue that may cause controversy and may not be supported by everyone. However we would ensure the patients are aware of what they are agreeing to and that they would have a right to withdraw at any time. If any unexpected pain or side effects were to become obvious in the patients during the trial it would be suspended. The results of the trial can only be applied to this form of leukaemia, and would also only come from a small amount of people. Although they would be valid for that, they could not be generalised for adult leukaemia, but it could give an idea of how the treatment would work in adults. Despite these implications, we believe the potential for benefits outweighs the potential of risks during the trial. Although there would be a small chance of the patients suffering an adverse reaction, the only other two outcomes are that the patients conditions do not change, or that they improve. Also, although this trial cannot take place for a number of years, we could spend this time wisely, planning the trial down to the finest detail, and finding the money to carry it out. 7
8 There are other positive things we could be doing in the time before the trial could take place. For example, we would raise awareness for the potential benefits of storing cord blood and promote it to the general public, at hospitals and blood banks. In years to come, we would hope that the majority of newborns have their cord blood stored, so that everyone can benefit from the unique properties of cord blood. As mentioned above, we would spend some of the time before the trial finding the money to carry it out. One of the ways we would hope to do this could be applying for grants, as the NHS may support this trial if it has the potential to produce a new treatment for leukaemia. Another way in which we would hope to get the NHS involved in our plans would be to suggest to them that they start storing cord blood in their teaching hospitals. As many people who will have their cord blood stored may never use it, it could be possible to ask people to donate their unused cord blood to research, and this could be stored in one or more NHS training hospitals, where research and training with cord blood could take place. We would hope that if our research gives the positive results we expect, it would persuade others to research the uses of cord blood in the treatment of other diseases, and this could be done in the NHS these hospitals. It is hopeful that in years to come, donating unused cord blood to medical research will become as common as organ donations, and that people could sign up to donating their cord blood when signing onto the donor register. We believe it would be very important to get the NHS as involved as possible in this research as ultimately cord blood could become a common treatment of many diseases, and hopefully this would be done in NHS hospitals, so that anyone can benefit from the many advantages of their own cord blood. Having NHS backing is useful as many people do not trust treatments, or are wary of them, if the NHS does not support them; it suggests there may be something wrong with the treatment, or that it is ineffective. Also, getting this treatment done privately without support from the NHS could cost a lot of money; therefore it is important that a patient has the choice to get such treatments done either with the NHS or privately. So to ensure patients have full trust in the safety and efficacy of the treatment, and have a choice in how and where they get this treatment, we would strive to get the NHS s full support. 8
9 Bibliography 1. Human Fertilisation and Embryology Authority (HFEA) Date accessed: February 2012 Date published: Genetic Science Learning Centre Date accessed: February 2012 Date revised: American Cancer Society Date accessed: February 2012 Date revised:01/23/2012 9
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