Cord Blood Transplantation

by Leonard Johnson, M.D.
Source: Fall 1999 CCCF Newsletter

The fact that cord blood (or blood from the placenta) contains stem cells that are identical to those present in bone marrow was first demonstrated over two decades ago. Subsequently it was shown that these cord blood cells could be stored for a long time. These two findings led to the first use of cord blood to successfully treat a five year old boy with a congenital form of marrow failure (called Fanconi Anemia), using cord blood from the birth of his sister, who was identical on tissue typing. By 1993 it had been shown that cord blood banking for unrelated transplantation was possible with the development of the first cord blood bank at the New York Blood Center. The ability to bank cord blood increases the chances of finding a source of stem cells for patients who could benefit from treatment by stem cell transplantation, particularly in certain ethnic groups under-represented in the unrelated bone marrow donor registries. The stored cells are immediately available in contrast to the time it takes to identify and obtain marrow from an unrelated marrow donor registry.

Two types of cord blood transplants can be performed: (i) using cord blood from a sibling in a family in which there is already a child affected by a disease which might benefit from stem cell transplantation; and (ii) using stem cells obtained from an unrelated donor cord blood bank. The diseases for which cord blood transplantation has been used are exactly the same as those treated by bone marrow transplantation: cancer (particularly leukemia), bone marrow failure (particularly aplastic anemia), diseases of the immune system, and a variety of genetic diseases.

There was initial concern that the volume of blood and number of stem cells that can be obtained from a cord blood unit (which averages less than half a pint) might not be sufficient to enable successful transplantation in adult patients. Successful transplants, however, have been reported in adult patients weighing over 180 pounds With appropriate treatment prior to cord blood transplantation, this will probably not prove to be a major problem.

A major advantage of using cord blood as a source of stem cells is that the severity of graft-versus-host disease, a major complication of marrow transplantation, appears to be less, even in mis-matched transplants. Children who have transplants using matched sibling cord blood appear to have less than a 10% chance of developing graft-versus-host disease, significantly less than observed using bone marrow from the same type of donor. The overall incidence of graft-versus-host disease in unrelated transplants, not unexpectedly, is higher; but the incidence of the most severe form also appears to be markedly less than that observed with using marrow from an unrelated marrow donor. Further experience will be needed, however, to determine the exact degree to which unrelated cord blood transplantation is associated with a smaller risk of life-threatening graft-versus-host disease when compared to marrow transplantation.

Overall, approximately 70-80% of patients who have been treated for non-malignant diseases and 30-40% of patients treated for malignant diseases are surviving. The complications for cord blood transplantation are the same as those of bone marrow transplantation. These include rejection, failure of the graft to function, infection, relapse in transplants for cancer, and side effects related to the preparative regimen before transplant. One potential problem with cord blood transplantation is that engraftment, particularly with platelets, appears to be slower than that associated with marrow transplantation, but usually this is not a clinical problem.

Cord blood transplantation, then, offers the major advantages of ease and safety of collection of a source of stem cells that it otherwise discarded, instant accessibility from a bank, a lower risk of viral contamination, a reduced risk of severe graft-versus-host disease, and the availability of more appropriate distribution of racial groups compared with unrelated marrow donor banks. Potential legal and ethical questions remain with the use of cord blood stem cells including the issues of informed consent and the need to follow donors to detect possible transmission of genetic or infectious diseases. Currently the National Institutes of Health are funding a study looking at issues of efficient blood banking and the use of these unrelated donor stem cells in a variety of childhood diseases.

Commercial companies have now been formed which offer parents the opportunity to store placental blood exclusively for the use of a member of the family into which the child is born. For fees ranging from $1250-1500 for the initial storage and $75-100/year storage, these companies claim that storing cord blood for the exclusive use of a family member serves as “biological insurance” for the child’s health. Their brochures claim that “Storing your baby’s cord blood is like saving for a rainy day. If your child develops a life- threatening illness that can use stem cells for treatment, the stored cells will be available. They can be a source of treatment for a variety of serious illnesses, including many forms of cancer, blood and immune system disorders, a safeguard against potential illnesses such as Hodgkin’s Disease, lymphoma, and leukemia. In the future, as your baby grows older, advances in medical technology are expected to expand the use of cord blood stem cells in the treatment of a broader range of cancer, genetic disorders and other diseases;” that “more than one in ten people may develop one of the severe illnesses that could be treated with cord blood stem cell therapy”, and, even if the cord blood is not used for the child for whose birth it was obtained, it “can generally be used for the mother of the child” if she develops “breast or gynecological cancer”. Additionally these companies claim that “your child’s banked cord blood provides a registered genetic identification source in cases of children who are lost, kidnapped or run away.” The most mis- leading claim is that “cord blood can be used to treat any cancer or genetic disease that is currently treatable by bone marrow transplantation” and that “the cord blood can always be used for the child from whom it was obtained.”

In fact, cord blood can only very rarely be used for the child from whom it was obtained because most diseases can only be successfully treated using stem cells from another individual (allogeneic transplants). It is expected that this will remain the situation for any disease that has a genetic basis (e.g. bone marrow failure, immune deficiency syndromes, sickle cell disease and thalassemia, and other genetic disorders of metabolism). The assumption that cord blood stem cells stored at birth might be useful for a child if a transplant is required to treat leukemia later in life is also very unlikely. In many studies the use of a patient’s own cells to treat leukemia (autologous transplants) has not proven any better than conventional therapy. If one examines the indications for allogeneic and autologous stem cell transplant, the only possible indication for storing a child’s stem cells for later use might be in the child who develops a malignant solid tumor such as a neuroblastoma or lymphoma, and this also remains debatable (Table I). Storing cord blood is unlikely to make a major impact in this situation because peripheral blood can now be used as a source of stem cells for the treatment of most solid malignant tumors.

Based on the incidence of various diseases, one can estimate the chances of a child developing a disease that may need treatment by stem cell transplantation. This risk is nothing like one in ten, but less than one in over 300. Thus, for every 200,000 babies born every year, approximately 600 would face the risk of developing a cancer or another potentially fatal disease that might eventually need treatment by stem cell transplantation. Two-thirds of these patients, however, would be cured with conventional therapy and would not require a transplant. Of the remaining 200 patients who might require a transplant, 66% would benefit only from an allogeneic transplant, and approximately 70 patients might benefit from an autologous transplant. Thus at most only 0.04% of the cord blood units stored for the baby’s exclusive use might actually be used--and this is very likely a gross overestimate.

Alternatively, if the cord blood stem cells were banked for use by any child who needed a stem cell transplant, the chance that those cells would be used productively is much greater. One can make a comparison with current blood banking practices. If blood banks were to store blood only for the exclusive use of the donor or the donor’s family, blood transfusion as we now know it, with its enormous potential to save lives, would no longer be available and effective, with obviously catastrophic consequences for many patients. Ideally, if the impact of cord blood transplantation becomes significant, the current national not-for profit blood banks would be the perfect repository for these units just as they are for other blood products.

There are two indications for family-exclusive cord blood storage: (i) in the family with a child already afflicted with a disease in which stem cell transplantation might become indicated or in families where both parents are known to carry the risk of a potentially lethal disease which could be treated by stem cell transplantation, even if they have not yet had an affected child. In these settings plans can be made in advance to store the placental blood, have it tissue typed and other relevant testing performed, and then used appropriately. Most transplant centers working in relationship with a not-for-profit blood bank can arrange this. Hopefully if the impact of cord blood transplantation grows, the national not-for-profit blood banks will be place in charge of these units, just as they are for other blood products.

In summary, storing cord blood for the exclusive use of a child or family member makes no sense medically and deprives other patients who might benefit from allogeneic cord blood transplantation from having the therapy available. So far there is not a single report of an autologous cord blood transplant using placental blood stored by one of these companies being used to treat a patient. Cord blood stored for the general community use in a not-forprofit bank, however, provides a very viable source of stem cells for stem cell transplantation, and potentially may make a significant impact on developing more accessible and safer stem cell transplantation.

**Update added 1/07. Article: "First report of autologous cord blood transplantation in the treatment of a child with leukemia." Pediatrics, 2007 Jan;119(1):e296-300. Hayani A, Lampeter E, Viswanatha D, Morgan D, Salvi SN. PubMed Abstract.

References:

  • Gluckman, E., et al. Outcome of cord blood transplantation from related and unrelated donors. New England Journal of Medicine 337:373-381, 1997.
  • Johnson, F.L. Placental blood transplantation and autologous banking - caveat emptor. Journal of Pediatric Hematology/ Oncology 19:183-186, 1997.
  • Additional references available upon request.

Note: A portion of the above article was published previously in the Blood & Marrow Transplant Newsletter, (1985 Spruce Avenue, Highland Park, IL 60035; (847) 831-1913 [phone]; (847) 831-1943 [fax]; e-mail: help@bmtinfonet.org; website: www.bmtinfonet.org/) Vol. 9, No. 3, October, 1998.

About the author: F. Leonard Johnson, M.D. is the Director of The Kenneth W. Ford Northwest Children’s Cancer Center, the Robert C. Neerhout Professor of Pediatrics and Chief of Pediatric Hematology/ Oncology at Oregon Health Sciences University, 3181 Sam Jackson Park Rd., Portland OR 97201

Glossary:

  • Allogeneic BMT: Any bone marrow transplant between two individuals, whether they are related or unrelated
  • Autolougous BMT: Marrow is removed from the patient during remission state, stored and then returned to the body after the patient receives high doses of chemotherapy and/or radiation therapy. On occasion, the re-infused marrow is purged of cancer cells before being returned to the patient.
  • CT: Confirmatory typing: A repeat tissue typing test done as one of the final tests to confirm the compatibility of the donor and patient prior to transplant.
  • GVHD: Graft versus host disease: A reaction of the transplanted marrow to the patient’s body, which can range in severity from a minor skin rash to life threatening disease involving major organs of the body.
  • HLA: Human leukocyte antigens: The proteins present on the surface of the body’s white blood cells which allow the body to recognize self vs. non self. An individual’s HLA type is inherited through the genes passed down from their parents. Perfect or near perfect matches reduce the level of GVHD. Includes identification of HLA A,B and DR antigens.
  • Stem cells or pluripotent cells: Cells which differentiate into the various blood cell lines of the body – lymphocytes, red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils.
  • Synergeneic: Donor marrow for transplant which is provided by monozygotic (identical) twin.
  • Peripheral blood stem cell transplant: Stem cells collected from the circulating blood stream that are then used as another retrieval source for either an autologous or allogeneic transplant.
  • Umbilical cord transplant: Stem cells collected from the placenta and umbilical cord, that are stored and later used for either autologous or allogeneic transplant.