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          Umbilical Cord Blood Banking

          A Rich Source of Stem Cells for Transplant

          By Debra Drew, NP

          Page 1
          This continuing education offering is sponsored by an unrestricted educational grant from CorCell. It is designed
          to educate nurse practitioners and other health care providers about umbilical cord blood banking. The author
          reports no real or perceived conflicts of interest that relate to this article.

          Objectives: The purpose of this article is to educate nurse practitioners about umbilical cord blood banking. After
          reading this article, the nurse practitioner should be able to

                 Discuss the types of UCB banks and their purposes.
                 List the advantages of UCB donation over bone marrow donation.
                 Describe the UCB collection process.
                 Describe the necessary components of parental education about UCB banking.

          In the early 1970s, bone marrow transplantation emerged as a viable treatment option for patients affected by a
          variety of malignant and nonmalignant hematologic diseases, congenital immunodeficiencies and tumors.1 The
          valuable stem cells harvested from bone marrow offered these patients hope for recovery and even remission.
          Stem cells are the building blocks of our blood and immune systems. The stem cells derived from umbilical cord
          blood (UCB) can also rebuild the immune system that is typically destroyed after a patient has received radiation
          or chemotherapy.

          History and Background
          Sixteen years ago, the first successful UCB transplant was performed in France to treat a boy with Fanconi's
          anemia.2 Since that time, research and clinical experience have demonstrated that UCB, which contains
          hematopoietic stem cells sufficient for transplant, may be a successful form of treatment for this cohort. For all
          diseases treated with UCB transplantation (Table 1), scientists have documented a 63% survival rate in patients
          treated with stem cells from a related donor (usually a sibling) and a 29% survival rate among patients
          transplanted with stem cells from an unrelated donor.2 These survival rates are comparable to that of bone
          marrow transplants. Based on the nearly 4 million births in the United States every year, storing umbilical cord
          blood from these infants could create an abundant source of stem cells for transplantation.3

          Allogenic (related or unrelated) and autologous (self) bone marrow are the usual sources of stem cells for
          transplantation. If autologous marrow is not an option, the next best choice for successful therapy is to harvest
          marrow from a sibling with an exact human leukocyte antigen (HLA) match. Close matching is vital for a
          successful transplant and drastically reduces the risk of the patient developing graft vs. host disease (GVHD), a
          reaction of T cells to HLA antigens in the recipient that can be fatal. Seven million HLA-A, HLA-B and HLA-DR
          donors are registered with international marrow donor registries. However, more than 30% of patients who
          require transplant therapy are unable to find a donor.4

          The National Marrow Donor Program (NMDP) is a nonprofit organization based in Minneapolis that facilitates
          marrow and blood stem cell transplants for patients who do not have a matched donor in their family. The NMDP
          maintains a list of potential donors, but its usefulness is limited by its ethnic homogeneity. Seventy percent of its 3
          million volunteer donors are Caucasian. For patients of other ethnic backgrounds, the odds of finding a match are
          approximately 20%.2

          The success of hematopoietic stem cell transplantation, regardless of the source of stem cells, relies on the
          development of a functional immune system derived from the donor cells. The production of granulocytes,
          platelets and red blood cells usually occurs quickly after transplant. However, the production of lymphocytes, in
          particular T lymphocytes, is delayed. The delay in production of these valuable cells may result in serious
          infection. The incidence of infection in the first 1 to 2 years following transplantation is about 50% in transplants
          from histocompatible sibling donors and 80% to 90% of recipients of matched, unrelated donor marrow
          transplants. The most common infectious agents in these cases are cytomegalovirus (CMV), herpes simplex

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          virus (HSV), varicella zoster virus (VZV), human herpes virus (HHV), respiratory syncytial virus (RSV), Coxsackie
          virus and Epstein-Barr virus (EBV).5

          UCB Transplants
          Since 1988, hundreds of lives have been saved by umbilical cord blood transplantation. The hematopoietic stem
          cells in UCB go on to mature into white blood cells that can fight infection and red blood cells that carry oxygen
          and platelets to aid in blood clotting after an injury. For a child with leukemia, the stem cells from a single
          placenta are sufficient to rebuild the blood and immune system. Before UCB transplantation was developed, a
          living donor was needed to provide stem cells from bone marrow.6

          Harvesting bone marrow from a donor is a lengthy and painful operative process, requiring hospitalization and
          anesthesia. Bone marrow is extracted from the iliac crest. As with any surgical procedure, side effects may
          include infection, bleeding, pain and fatigue.2

          Umbilical cord blood offers several advantages over other sources of stem cells:2, 7

                 The collection process is relatively simple.
                 The collection process poses no risk for mothers and donors.
                 UCB donation is associated with a lower risk of GVHD.
                 The criteria for HLA matching in donor-recipient selection are less stringent.
                 There is a lack of donor attrition.
                 UCB donation and collection cost less than bone marrow donation and collection.
                 UCB donation has a reduced likelihood of transmitting infections such as cytomegalovirus or Epstein-Barr
                 virus.2, 7
          Page 2
          Among patients who receive a stem cell transplant, CMV and other viruses are associated with significant
          morbidity and mortality. Another major benefit to umbilical cord blood is its reduced immunoreactivity, which
          lessens the risk of rejection by the recipient.7 UCB is richer in stem cells, also known as CD34 cells, than adult
          blood or bone marrow.7

          Researchers have documented the incidence of GVHD in children who have received UCB and compared it with
          GVHD incidence in children who received bone marrow transplantation.8 Both groups received their stem cells
          from HLA-A identical siblings. The incidence of grade II through IV GVHD was 14% in the UCB group and 24% in
          the bone marrow group. The authors concluded that there was a lower incidence of acute and chronic GVHD in
          the recipients of UCB compared with patients who received bone marrow transplantation.8

          A 100-mL unit of UCB contains one-tenth the number of nucleated cells and CD34+ cells present in 1,000 mL of
          marrow. Because they multiply rapidly, the stem cells in a single unit of UCB can rebuild the entire hematopoietic

          Another advantage of umbilical cord blood is that it can be collected, tested and available in a matter of weeks. In
          the bone marrow donation process, the length of time from donor selection to procurement of bone marrow
          typically takes 4 to 6 months. Among patients who decide to undergo bone marrow transplantation, only 5% are
          able to identify a match within 2 months. Fifty percent of patients identify a donor within 4 months, and 95% of
          patients are able to identify a donor within 16 months.10 Locating a match for ethnic and racial minorities is even
          more difficult, furthering the delay to transplantation.

          The process to harvest stem cells from bone marrow takes significantly longer than from umbilical cord blood,
          and many patients have died during the long search for a marrow donor with a matching tissue type. The speed
          and efficiency of stem cell procurement is critical for patients whose disease requires immediate therapy.

          While the clinical data for umbilical cord blood transplantation among children is encouraging, few studies have
          examined the use of umbilical cord blood transplants for adults. One study followed 68 patients with
          life-threatening hematologic disorders treated with intensive chemotherapy or total body irradiation who received
          transplantation of HLA mismatched UCB.11 The researchers measured outcomes by hematologic reconstitution,
          the occurrence of acute or chronic GVHD, relapses and event-free survival. Acute GVHD occurred in 11 of 55
          patients within the first 100 days following transplantation. For those who survived longer than 100 days
          post-transplantation, chronic GVHD occurred in 12 of 33 patients. Eighteen of the 68 patients (26%) were
          disease-free 40 months after transplantation. The authors concluded that these were acceptable rates of acute
          and chronic GVHD and stated that the presence of a high number of CD34+ cells in the graft was associated with
          an improvement in survival.11 Older allogenic recipients have been successfully treated with UCB
          transplantation, but these patients had a variety of less intense non-myeloablative conditioning regimens.11

          The largest study of transplantation was conducted by investigators from the University of Minnesota on a cohort
          of high-risk patients with hematologic malignancies.5 In this study, researchers transfused unrelated UCB into 43

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          patients, ages 22 to 65 years (median age 49.5). The cumulative incidence of grade II through IV GVHD was
          44% and grade III through IV was 9%. Although 93% of the recipients had a 1-2 HLA mismatched graft, the
          survival rate at 1 year post-transplant was 24%.5

          Informed Consent
          Clearly, placental blood can be a valuable source of stem cells, rather than a mere waste product. Because
          collected placental blood is tested for various infectious diseases, including human immunodeficiency virus and
          hereditary hematologic diseases, it should not be collected without written informed consent from the mother. The
          informed consent must include statements of what the blood is being tested for and how the mother will be
          informed of the test results.

          The collection of UCB along with an extensive family history raises issues about the mother's privacy. If the
          placental blood is linked to the donor, screening could potentially disclose private medical information. Either the
          mother must consent to perform the screening tests and create this medical information or the UCB must be
          stripped of all identifiers so that the blood cannot be linked to the source.12 Some researchers have suggested
          that the ability to link UCB to its donor in research projects be maintained but that security measures be taken to
          protect the donor's identity. Others believe that all identifiers should be removed for the purpose of research so
          that the blood can be freely tested without simultaneously testing the child and the mother.
          Page 3
          Education of Parents
          Expectant parents need education about the types of UCB donation and banking available today, along with
          associated costs (Table 2).13 Nurse practitioners are ideally suited to address these issues with expectant
          mothers as early in pregnancy as possible, to allow them time to consider all options. The peripartum period is a
          stressful time for most women and is not the appropriate time to approach mothers for informed consent.
          Identifying intent early in the pregnancy will allow time for informed consent, a thorough family medical history,
          and education for the provider who will deliver the infant. The receiving cord blood bank also needs time to make
          arrangements for accepting and processing the blood.

          Collection Process
          Umbilical cord blood collection may be performed after the delivery of the infant with the placenta in utero, or after
          the delivery of the infant and placenta. There is no risk or discomfort for the baby, since the cord blood is
          collected after the birth and after the umbilical cord is clamped and cut. Collection should only be performed after
          the delivery of healthy, full-term infants.

          Once the infant is delivered, time to clamping of the umbilical cord determines the amount of blood volume
          obtained. If the umbilical cord is clamped too soon after delivery, the infant may be deprived of much needed
          blood and become anemic. This practice would increase the amount of blood volume available for donation, but
          placing the infant at risk this way is considered unethical and dangerous. The standard recommendation is that
          clamping should be done within 30 seconds of delivery for optimal collection.7

          During vaginal deliveries, holding the baby below uterine level and then clamping the cord has been associated
          with increased placental blood volume. UCB may also be collected with the placenta in utero. Experts believe that
          in-utero collection facilitates blood collection by the squeezing of the placenta during uterine contractions.

          A closed collection system should be utilized to prevent bacterial and maternal fluid contamination. The system
          consists of a venipuncture device attached to tubing that leads to a collection bag, similar to a blood donation set.
          Collection is performed by a phlebotomist, who punctures the umbilical vein after disinfecting the site. The blood
          is then simply collected by gravity. The collection process takes approximately 5 to 10 minutes; some milking of
          the cord may be necessary. An anticoagulant and tissue culture medium are added to the collection bag using
          sterile technique.

          About 50% to 70% of donated units are ineligible for storage due to low volume. Each unit of donated UCB must
          contain at least 40 mL to treat a child weighing up to 30 kg, and more than 70 mL is needed to treat an adult.14
          To date, most of the patients who have received umbilical cord blood stem cell transplants have been small

          Extensive ongoing clinical and laboratory research is now being conducted to determine strategies to allow
          allogenic UCB donor engraftment that would provide a wider application of these stem cells for patients who
          would benefit from this form of therapy.

          A National Network
          Rapidly growing interest in cord blood banking has led to action by politicians in Washington, D.C. In 2004,
          legislation that would establish a national cord blood stem cell bank network was introduced in both houses of
          Congress. This new program would be housed within the Health Resources and Services Administration (HRSA).
          As of press time in February, Congress had not yet voted on the bill to create a national network.

          Meanwhile, the Institute of Medicine (IOM) is working to provide HRSA with an assessment of the status of

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          existing cord blood programs and inventories and to make recommendations to enhance the structure, function
          and utility of this resource. The committee appointed by IOM has involved experts in fields including medicine,
          bioethics, statistics, clinical outcomes, medical database development, obstetrics, cord blood banking, stem cell
          biology, clinical research design, blood and marrow banking operations, and HLA typing for transplantation.

          Patient Education
          The need for thorough patient education about cord blood banking is an evolving issue in women's health and
          pediatric settings, and nurse practitioners are ideally suited to provide these services. Commercial UCB banks
          are often the primary source of information for parents, but they would benefit as well from education by a health
          care provider who can discuss all relevant medical issues, including the relatively small chance that their children
          will need a UCB transplant by age 18.3,10,15 The American Academy of Pediatrics issued a subject report on
          cord blood banking in 1999, and is in the process of updating it in light of recent research and use.

          All health care providers who work with expectant parents should present the option of UCB donation or banking,
          along with thorough education so that they can make an informed choice. A helpful resource is a Web site called
          Parent's Guide to Choosing a Cord Blood Bank ( The site is maintained by
          Frances Verter, PhD, a founder of the Umbilical Cord Blood Education Alliance, and it presents objective
          information about UCB banking.

          The limitless value of the stem cells derived from UCB is clear. The important functions of these cells for clinical
          advancement and research are just beginning to be appreciated. Nurse practitioners play a vital role in
          advocating for their patients by helping parents become educated consumers.

          Debra Drew is a neonatal nurse practitioner who is a research coordinator at Maine Medical Center in Portland,
          1. Burgio G, Gluckman E, Locatelli, F. Ethical reappraisal of 15 years of cord-blood transplantation. Lancet.

          2. Wolf S. Cord blood stem cell banking. American Journal of Nursing. 1999;99(8):60-67.

          3. Ellenchild-Pinch W. Cord blood banking: ethical implications. American Journal of Nursing.

          4. Wagner J, Barker J, DeFor T, Baker K, Blazer B, Erdi C, Goldman A, Kersey J, Krivitt W, Davies S.
          Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant
          diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood.

          5. Chao N, Emerson S, Weinberg K. Stem cell transplantation (cord blood transplants). Hematology.

          6. Kline R. Whose blood is it, anyway? Scientific American. 2001;284 (4):42-49.

          7. Gonzalez-Ryan L, Coyne K, van Syckle, K, Glover N. Umbilical cord blood banking: procedural and ethical
          concerns for this new birth option. Pediatric Nursing. 2000;26(1):105-110.

          8. Rocha V, Wagner J, Sobocinski K, Klein J, Zhang M, Horowitz M, Gluckman E. Graft-versus-host disease in
          children who have received a cord blood or bone marrow transplant from an HLA-identical sibling. NEJM.

          9. Gluckman E. Hematopoietic stem-cell transplants using umbilical-cord blood. NEJM. 2001:344(24):1860-1861.

          10. American Academy of Pediatrics Work Group on Cord Blood Banking. Cord blood banking for potential future
          transplantation: subject review. Pediatrics. 1999;104:116-118.

          11. Laughlin MJ, Barker J, Bambach B, Koc O, et al. Hematopoietic engraftment and survival in adult recipients
          of umbilical-cord blood from unrelated donors. NEJM. 2001;344(24):1815-1822.

          12. Annas G. Waste and longing: the legal status of placental-blood banking. NEJM. 1999;340(19):1521-1524.

          13. Fernandez C, Gordon K, Van den Hof M, Taweel S, Baylis F. Knowledge and attitudes of pregnant women
          with regard to collection, testing and banking of cord blood stem cells. Canadian Medical Association Journal.

          14. Cord blood banks. The Medical Letter on Drugs and Therapeutics. 2001;43(1114):84-86.

          15. Perlow J. Cord blood banking: an OB's perspective. Contemporary OB/GYN. 2002;47(11):31-43.
          List of Tables

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Table 1
Conditions That Are Sometimes Treated With Stem Cell Transplantation
Malignancies                     Blood Disorders                      Metabolic Disorders               Immunodeficiencies
◗ Acute lymphocytic leukemia     ◗ Amegakaryocytic thrombocytopenia   ◗ Adrenoleukodystrophy            ◗ Adenosine deaminase deficiency
◗ Acute myelogenous leukemia     ◗ Aplastic anemia                    ◗ Bare lymphocyte syndrome        ◗ Severe combined
◗ Chronic myelogenous leukemia   ◗ Congenital cytopenia               ◗ Ceroid lipofuscinosis             immunodeficiency
◗ Myeloplastic syndrome          ◗ Diamond-Blackfan anemia            ◗ Gunther s disease               ◗ Wiskott-Aldrich syndrome
◗ Neuroblastoma                  ◗ Evan s syndrome                    ◗ Dyskeratosis congenital         ◗ Duncan s disease
◗ Non-Hodgkin s lymphoma         ◗ Fanconi s anemia                   ◗ Erythrophagocytic
                                 ◗ Kostmann syndrome                    lymphohistiocytosis
                                 ◗ Sickle cell anemia                 ◗ Gaucher s disease
                                 ◗ Thalassemia                        ◗ Hunter s syndrome
                                                                      ◗ Hurler s syndrome
                                                                      ◗ Krabbe s disease
                                                                      ◗ Langerhans cell histiocytosis
                                                                      ◗ Lesch-Nyhan syndrome
                                                                      ◗ Leukocyte adhesion deficiency
                                                                      ◗ Neuronal lipofuscinosis
                                                                      ◗ Osteopetrosis
                                                                      ◗ Sanfilippo s syndrome
                                                                      ◗ Scheie s syndrome
                                                                      ◗ Wolman disease
Table 2
Types of Umbilical Cord Blood Banking
Type                       Purpose                                 Fee
Autologous Blood Banking    akn o ef n h vn ht ef r aiy ebr
                           Bnigfrsl i teeetta sl o fml mme          aibe sal novs n nta e
                                                                   Vral.Uulyivle a iiilfe
                            ed  tm el rnpat
                           nesase cl tasln                         and a yearly maintenance fee.

 lritc r loei
Atusi o Algnc              Banking for use by the general public    o e
                                                                   N fe
Blood Banking

Research Blood Banking      akn o       pcfc eerh nttto r eea
                           Bnigfraseii rsac isiuino gnrl            o e
                                                                   N fe
                           research purposes

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