Cord Blood Stem Cell Transplants and the Treatment of Adult Leukemia

By

Amy Phillips

Research in Allied Health

Dr. Masini

Fall 2005

Abstract

            Stem cell research is on the rise in order to develop new treatments for diseases and injuries.  Cord blood (blood left over from the umbilical cord) is rich with stem cells.  Researchers are discovering new ways to use cord blood in the treatment of adults with leukemia.  Leukemia is a cancer of the blood-forming tissues of the body (1).  Research shows that by obtaining two units of cord blood and combining them, there are enough stem cells to successfully treat adult leukemia (2).  Of the research I found, the most successful form of treatment is a bone marrow transplant from a matched donor.  However, cord blood transplants using two units had almost the same results of those receiving bone marrow transplants from imperfectly matched donors.  For most considering cord blood transplants, it is an absolute last resort (3).  Success rates are higher with matched bone marrow transplants.  However, any type of treatment is better than no treatment and cord blood transplants give hope to adults battling this deadly cancer. 

Introduction

            Stem cell research is a very controversial topic in the United States as well as in the world.  Stem cells are “master cells” that can generate different types of cells within the body (4).  The focus of this research is cord blood.  Cord blood is the blood left over in the umbilical cord at the time of birth.  This blood is rich with stem cells that can be used in the treatment of many diseases including Leukemia and sickle-cell anemia (4).  Studies have even shown that the body’s immune system originates from cord blood and can treat other diseases, not just immune or blood disorders (5).  There is clinical evidence that these stem cells can generate into brain, liver, heart, and bone cells.  Much of the controversy regarding this topic has to deal with the ethical and moral dilemma.  Some stem cell research comes from the cloning or copying of embryos for the purpose of medical experimentation.  However, not all stem cell research is dependent on cloning.  The purpose of this research is to educate others about the process of cord blood stem cell transplantation and its benefits.  I will be focusing on cord blood as a treatment for adult leukemia.

Problem Statement

            Cord blood has been used successfully in the treatment of leukemia in children.  However, this treatment has not been a recommended choice for adults.  This is because it is difficult to obtain a dose large enough to successfully treat adults (cord blood contains about 1/10 the number of useable stem cells as bone marrow) (3).  Researchers are now trying to solve this problem by combining two cord blood units from different donors for the stem cell transplant.  Is this promising treatment, once limited to children, now open to all patients, including adults?  Does it show similar results in children as well as adults?  I intend to answer these questions and give valid research findings in order to inform others about the recent findings in this extremely promising treatment.

Review of Literature

            Leukemia is a cancer of the blood-forming tissue (1).  An example of this tissue is bone marrow.  Bone marrow produces three types of blood cells.  These cells are red blood cells, white blood cells, and platelets.  All blood cells begin as stem cells in the bone marrow.  Stem cells are immature cells that can develop into any type of cell in the body.  They are often referred to as “master cells.”  When needed, the body signals these stem cells within the bone marrow to mature into any of the three types of blood cells (1).  In patients with leukemia, these blood cells are abnormal and cannot function properly. 

            There are several options for the treatment of leukemia.  One treatment is a stem cell transplant.  This is possible through a bone marrow transplant from a healthy adult or from the cord blood of a newborn (6).  While cord blood transplants have been used successfully in the treatment of a child with leukemia, it has not been recommended for the use of an adult with leukemia.  However, researchers are finding that cord blood is now a feasible option for the treatment of adult leukemia.  Researchers from the University of Minnesota began combining cord blood from two different donors in order to obtain a sufficient amount of stem cells.  Their study was published in the issue of Blood, the official journal for the American Society of Hematology.  In this study, twenty-three patients were studied for a period of over two years.  For each patient, a match could not be made possible from an adult volunteer.  Cord blood, on the other hand, is more tolerant of differences between the donor and patient because the stem cells are so immature.  Dr. John Wagner, Scientific Director of Clinical Research of the UM Blood and Marrow Transplantation Program and Stem Cell Institute, concluded that these patients could still have successful transplants from two partially-matched units of cord blood.  Unfortunately, two patients died shortly have the transplant due to infection.  However, for the remaining twenty one patients, the transplanted stem cells began to produce normal, healthy cells.  After one year, fifty-seven percent of the patients were disease free.  The success rate rose to seventy-two percent for those who received the transplant while their cancer was in remission (7).  

            There are several advantages to cord blood transplants.  First, there is no threat to the donor.  It is painless and non-invasive.  Secondly, once cord blood is collected, it is frozen and stored in a cord blood bank ready for use.  This means that it can take less time for a patient to receive a transplant.  With bone marrow transplants, a search must be made from national and international databases, which may take a substantial amount of time (7).

            Even though there is plenty of promising research about this treatment, I did find a study that compared three types of stem cell transplants in which cord blood transplants weren’t necessarily the best treatment.  Mary J. Laughlin, MD, associate professor of medicine at Case Western Reserve University School of Medicine, conducted a study comparing 600 leukemia patients who received either one of three transplants.  These transplants included bone marrow from a matched (but unrelated) donor, a bone marrow transplant from an imperfectly matched (and unrelated) donor, or a cord blood transplant.  This study was to compare the success rate between the different available transplants.  Patients who received the matched marrow had the best results.  Three years after treatment, thirty-three percent of them were still disease-free.  However, there were few differences between the patients who received unmatched marrow and those who received a cord blood transplant.  After three years, about twenty-two percent in each group were disease-free.  However, this study revealed a concerning figure.  Those who received cord blood transplants were at a higher risk for infections than those who received a bone marrow transplant (3).  This is because the stem cells in cord blood are much less developed than those from the bone marrow from a healthy adult.  As a result, it takes more time for the levels of blood platelets and white blood cells to return to a normal level leaving the patient susceptible to deadly infections.  In Laughlin’s study, infection as a cause of death in the first 100 days following transplant was higher in the cord blood group (45% of deaths) than either of the bone marrow groups (21% for matched marrow and 24% for mismatched marrow)(3).

            Even though there are few differences in the long term results of cord blood transplants and bone marrow transplants, the short term results can be deadly due to infection.  As a result, after a cord blood transplant, patients are now being given growth factors in order to stimulate the production of white blood cells and platelets (3).  Now that patients are given these growth factors, it takes less time for cord blood recipients to develop an immune system able to fight infections. 

            When deciding which type of transplant is right for a patient, it is important to consider the risk of graft-versus-host disease (GVHD).  An advantage of a cord blood transplant is the cord blood has a relatively low number of immune T-cells (2, 10).  T-cells are white blood cells and are one of the most powerful cells of a person’s immune system.  If a donor and a recipient have too many differences, the T-cells from the donor will attack the patient’s body because it is recognized as a “foreign body,” resulting in GVHD.  These cells play a key role in GVHD which can kill between twenty and forty percent of the patients it affects.  Since cord blood as a low number of T-cells, the “threshold for a proper match between donor and patient is much lower than if cells were sourced from adult bone marrow” (2). 

            There are two types of GVHD, acute and chronic.  Acute GVHD occurs within the first three months and may cause irritation and allergies.  Rashes may also cover the skin which can develop into blisters and can also affect the stomach, liver, and intestines.  Chronic GVHD occurs after three months following transplantation.  Not only does it carry the same side effects as acute GVHD, but it also affects the salivary glands, mucous glands, and glands that lubricate the lining of the stomach and intestines (8). 

            There have been studies conducted to compare the rates of GVHD with bone marrow transplants and cord blood transplants.  In one particular study, researchers compared the records of 113 children who received cord blood transplants from siblings with over records from over 2,000 children who received bone marrow transplants from siblings.  The rate of acute GVHD in children with cord blood transplants was fourteen percent while those receiving bone marrow transplants rose to twenty-four percent.  Of the children who lived more than 90 days after the transplant, only six percent developed chronic GVHD while fifteen percent of bone marrow recipients developed chronic GVHD (9).  Unfortunately, I could not find a study comparing the rates of GVHD in adults receiving either a bone marrow transplant or cord blood transplant. 

            In one article, I found a particularly interesting fact.  With transplants containing two different units of cord blood, both units will begin to produce healthy, functioning blood cells over the first few months.  However, one unit will become dominate and actually take over the other.             There is no way of predicting which unit will become dominate.  It has been determined that there are no extra complications of using two units of cord blood over one unit (2).

            I wanted to compare the results of cord blood transplants in children and adults with leukemia.  However, I never found a study that actually compared the two.  Even though I did find separate studies and information about the success of this treatment in both children and adults, I am hesitant to compare these results in this research paper due to the different circumstances for each study.  I do not want to present misleading statistics and information.  Since I cannot verify that each study was done in the exact way, I will not compare them.

Methods

            The purpose of my study is to compare the different types of stem cell transplants available to adults suffering from leukemia.  This study is nonexperimental research and would be referred to as ex post facto research.  This is because the independent variable (leukemia) has already happened. I would submit my study to the university IRB and comply with all HIPPA guidelines regarding patient confidentiality.  I am replicating a study I found during my research headed by Mary J. Laughlin and published in the New England Journal of Medicine (Vol. 351, No. 22:2265-2275).  There will be three groups: those receiving a matched bone marrow transplant, those receiving an imperfectly matched bone marrow transplant, and those receiving a cord blood transplant containing two units of cord blood.  In my study, there will be no control group.  Not only would it be unethical to withhold treatment to leukemia patients, but it also is irrelevant to the purpose of this study dealing with the different forms of transplants.  This is considered a correlational study because there is more than one variable.  After the transplant, patients will be followed for a minimum of three years.  Infection, disease-free survival, relapse, and transplant-related deaths will be measured separately in all three groups.  This is considered to be nominal date and the statistical findings are classified as nonparametric.  In order to ensure validity of my study, I will carefully pick my subjects and try to prevent historical contamination.  In the original study, the researchers believed the two units of cord blood would be an effective treatment, but did not know how it would hold up against bone marrow transplants.  In my results, I hope to have the same findings as the original study.  The chances of survival were similar between the cord blood recipients (approximately 22%) and the mismatched bone marrow recipients (approximately 22%).  Those receiving matched bone marrow had the highest survival rate of 33% after three years.  However, infection as a cause of death in the first 100 days following the transplant was significantly higher in cord blood recipients (approximately 45% of deaths) than either of the bone marrow groups (21% for matched bone marrow and 24% for unmatched bone marrow)(3).  If my study resulted in similar findings this would increase the reliability of the original study which concerns with the replicability of scientific findings.

Conclusion

            All of the studies I found recognized cord blood transplants as a successful treatment for adult leukemia.  Even though one unit of cord blood does not contain enough stem cells to treat an adult, studies show combining two units offers a chance of survival.  Even though matched bone marrow is the most successful, many patients cannot find a match.  For every ten patients needing a bone marrow transplant, only two will find a bone marrow match (2).  With that in mind, studies show that cord blood transplants may be more beneficial than mismatched bone marrow transplants due to the decreased risk of GVHD even though both have similar success rates.  This provides many adults suffering from leukemia with treatment options that might give them another chance at life.

References

American Cancer Society (2004).  Cord Blood Transplants Help Adults with Leukemia.    

            Retrieved November 6, 2005 from World Wide Web:              http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Cord_Blood_Transplants_Hel            p_Adults_with_leukemia.asp .(3)

Barclay, Laurie (2001).  High-Risk Procedure pays off for Leukemia Patient. Retrieved      November. 6, 2005 from World Wide Web:       http://aolsvc.webmd.aol.com/content/article/33/1738_81494.htm. (5)

Chao, Nelson J. (2004).  Stem Cell Transplantation (Cord Blood Transplants). Retrieved on          November 10, 2005 from World Wide Web:             http://www.asheducationbook.org/cgi/content/full/2004/1/354. (10)

Griffin, R. Morgan (2005).  Cord Blood Stem Cells: Your Questions Answered.  Retrieved            November 5, 2005 from World Wide Web:          http://aolsvc.health.webmd.aol.com/content/article/109/109262.htm?printing=true. (4)

Leukemia Patients Treated with Cord Blood Face Lower Risk of Complications. (2000).     Retrieved November 21, 2005 from University of Minnesota Cancer Center Website:             http://www.cancer.umn.edu/page/news/GVHDstudy.html. (9)

McFarland, Helen M. (n.d.). Oncology: Thalidomide, Stem-Cell Transplantation, and Leukemia    Updates. Retrieved on November 14, 2005 from MedScape Database:    http://www.medscape.com/viewarticle/418739. (8)

Mundell, E.J. (2005).  New Approach Works Against Leukemia, Lymphoma. Retrieved      November 10, 2005 from World Wide Web: http://ww.hon.ch/News/HSN/526565.html.         (2)

Stark, Laura. (2005). Cord Blood Transplantation Now a Viable Option for Adult Leukemia           Patients.  Retrieved on November 21, 2005 from World Wide Web:             http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=19066. (7)

Warner, Jennifer. (2004). Cord Blood Transplants Realistic Option for Adult Leukemia       Treatment. Retrieved on November 10, 2005 from World Wide Web:             http://aolsvc.health.wedmd.aol.com/content/article/97/104256.htm. (6)

What is Leukemia? (2005) Retrieved on November 6, 2005 from World Wide Web:             http://www.mdanderson.org/departments/leukemia/print.cfm?dIndexPrint=1&pn=A8426.            (1)