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Summer 1996Volume 3, Number 1 |
Bone marrow transplantation (BMT) is often the preferred method of treatment for a variety of blood disorders including certain leukemias, aplastic anemia, and inborn errors of metabolism (such as thalassemia major, Hurler's Syndrome, and severe Gaucher's disease). Generally, BMT consists of administering high doses of chemotherapy and/or irradiation to destroy abnormal cells in the patient's bone marrow and then transfusing pluripotent blood stem cells (often referred to as pluripotent hematopoietic stem cells, or PHSC) from a tissue- (HLA-) matched donor, usually a sibling, in order to replace the normal blood elements. Because most patients do not have an acceptable matched, related donor, the National Marrow Donor Program has been established to match volunteer bone marrow donors with potential recipients who require BMT. The registry is currently composed primarily of Caucasians of Western European descent, making it extremely difficult to find potential donors for ethnic minorities.
Recently, several investigators have shown that umbilical cord blood is a rich source of pluripotent stem cells and can be used in place of bone marrow in transplantation. To date, umbilical cord blood has been used in sibling and other related donor transplants.1-4
| Additionally, evidence is accumulating that cord blood transplant recipients have a lower risk of developing graft-versus-host disease (GVHD), a debilitating and sometimes fatal complication that occurs when donor blood cells attack various host body tissues. |
Extending the use of cord blood to unrelated donor transplants would greatly facilitate the identification and procurement of pluripotent stem cells required for BMT for large numbers of patients for whom no acceptable family donor is available. The use of cord blood for transplantation would be facilitated if it were possible to create a "bank" of cord blood in a cryopreserved state. Cord blood could therefore be used for transplantation in related allogeneic, unrelated allogeneic, and autologous transplants. Autologous cord blood collections could also be used as insurance against future illness requiring pluripotent stem cell support or as targets for gene therapy (the genetically altered stem cells could then be infused into the patient).
Cord blood is easily collected after delivery without pain or risk to either the mother or the newborn infant. A pilot program at the New York Blood Center has been banking, HLA-typing, and cryopreserving cord blood collected in delivery rooms of area hospitals. Other banking centers are being established throughout the country. About 4.5 million babies of virtually all ethnic origins were born in the United States last year, and cord blood from these populations should make it easier to find HLA-matched donors for ethnic minorities.
Additionally, evidence is accumulating that cord blood transplant recipients have a lower risk of developing graft-versus-host disease (GVHD), a debilitating and sometimes fatal complication that occurs when donor blood cells attack various host body tissues.3-7 The mechanism(s) by which the risk of GVHD is lessened in cord blood transplants is not well understood, but several investigators have proposed that the pluripotent stem cells in cord blood are immunologically immature compared with those derived from older donors and therefore less likely to attack the patient's tissues. Preliminary data also indicate that the stringency of the HLA tissue match between the donor and recipient may be less in cord blood transplants.5,7 Therefore, it may be even easier to identify potential donors from a cord blood bank.
| Preliminary data also indicate that the stringency of the HLA tissue match between the donor and recipient may be less in cord blood transplants. |
At present, bone marrow donors have to undergo either general or regional anesthesia in order to obtain from their posterior hip bones the large volume of marrow needed. Alternatively, they may receive daily injections of a drug called granulocyte-colony stimulating factor (Neupogen®, Amgen Corp.) for several days. Granulocyte-colony stimulating factor mobilizes pluripotent stem cells into the peripheral blood, which can then be collected during apheresis. These sometimes uncomfortable and often time-consuming procedures would be unnecessary if a cord blood transplant could be performed.
The major limitation to the use of cord blood for pluripotent stem cell transplants may be the volume of cells needed and patient size. Typically, 100-120 cubic centimeters (cc) of cord blood can be obtained from the umbilical cord at the time of delivery; this blood is rich in pluripotent stem cells. However, the number of pluripotent stem cells needed for transplantation depends on the recipient's size, and it is unclear if enough of these cells can be obtained from cord blood for transplantation into an adult patient. To date, the majority of cord blood transplants have been performed in children and adolescents, although recently a number of adults have received such transplants with preliminary data indicating successful engraftment in most recipients.1-4,7
In summary, cord blood represents a source of pluripotent stem cells which may be utilized in allogeneic related and unrelated transplants as well as in autologous transplants. Furthermore, autologous pluripotent stem cells obtained from cord blood may represent potential targets for gene therapy. Cord blood banking will greatly enlarge the available donor pool for transplantation, and the requirements of HLA matching may be less stringent when pluripotent stem cells are used.
Jay Feingold, MD, PhD
Director, Pediatric Bone Marrow Transplant Program
University of Connecticut
Farmington, Connecticut
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