American Academy of Pediatrics Policy Statement January 2007 Pediatrics Volume 119
INTRODUCTION
In a number of genetic, hematologic, immunologic, metabolic, and
oncologic disorders, reconstitution of bone marrow (transplantation) can be
a potentially life-saving procedure. Allogenic(others) (Others - related or
unrelated) or autologous (self) bone marrow or peripheral blood stem cells
are the usual sources of hematopoietic progenitor cells to achieve this
goal. If autologous(self) stem cells are not available or cannot be used,
the best option for successful reconstitution therapy is to secure stem
cells from an HLA-matched sibling. Close matching confers a higher
probability of successful engraftment and minimizes the risk of potentially
fatal graft-versus-host disease. Unfortunately, there is only a 25% chance
for identify-ing a full HLA match in a sibling donor.
An alternative to a related donor involves seeking unrelated HLA-matched
adult allogenic(others) donors outside of the family. There are more than 7
million potential unrelated volunteer adult donors registered in the
National Marrow Donor Program registry. Although the number of patients who
receive unrelated adult allogenic(others) donor stem cell transplants
continues to increase each year, many patients are unable to find a fully
matched donor, which diminishes access to transplantation therapy. Nonwhite
patients have a lower chance of identifying a fully matched unrelated adult
donor because of genetic heterogeneity and lack of non-white donors. Over
the past decade, unrelated-donor, banked umbilical cord blood has been shown
to contain sufficient numbers of stem cells for successful transplantation
between unrelated, partially HLA-mismatched individuals. With advances in
the clinical practice of cord blood transplantation, most patients unable to
find a fully matched adult donor can identify a partially matched cord blood
donor.
Recently, it was shown that umbilical cord blood contains a sufficient
number of hematopoietic stem cells to be used for transplantation. More than
5500 unrelated-donor cord blood stem cell transplants for a variety of
pediatric genetic, hematologic, immunologic, metabolic, and oncologic
disorders have been performed to date (Table 1). The 1-year survival may be
as high as 75% to 90% after sibling HLA-matched cord blood donor stem cell
transplantation and 40% to 80% after unrelated cord blood stem cell
transplantation. Advantages of the use of cord blood include the fact that
it is readily available, carries less risk of transmission of blood-borne
infectious diseases, and is transplantable across HLA barriers with
diminished risk of graft-versus-host disease compared with similarly
mismatched stem cells from the peripheral blood or bone marrow of related or
unrelated donors. Autologous(self) stem cells have been used for gene
therapy in infants with severe combined immunodeficiency, but the appearance
of T-lymphocyte leukemia in some patients has indicated the need for more
basic research before additional clinical trials of gene therapy can be
undertaken.
Since the first unrelated cord blood-banking program was started at the
New York Blood Center in 1991, a number of public cord blood-banking
programs have been established throughout the world to collect, type, screen
for infection, and cryogenically store cord blood for potential
transplantation to unrelated and related recipients. Some of these programs
had been funded by the National Heart, Lung, and Blood Institute (Na-tional
Institutes of Health), the National Marrow Donor Program, the American Red
Cross, or academic programs based in not-for-profit organizations. One cord
blood program initiated by the National Institutes of Health exists solely
for sibling donor collection for families who are likely to consider cord
blood transplantation because a first-degree relative has been diagnosed
with a disease that is treatable with allogenic(others) transplantation. In
this bank, families own the cord blood, and it is shipped to a designated
transplant center in the event a medical decision to proceed with cord blood
transplantation is made.
TABLE 1
Diseases Treatable With Umbilical Cord Blood
Transplantation
Malignancles
Bone marrow failure
Hemoglobinopathies
Immunodeficiencies
Inborn errors of metabolism
A number of private for-profit companies have been established that
encourage parents to bank their children's cord blood for their own
autologous(self) use or for directed donor allogenic(others) use for a
family member should the need arise. Parents have been encouraged to bank
their infants' cord blood as a form of "biological insurance." Physicians,
employees, and/or consultants of such companies may have potential conflicts
of interest in recruiting patients because of their own financial gain.
Annual disclosure of the financial interest and potential conflicts of
interest must be made to institutional review boards that are charged with
the responsibility of mitigation of these disclosures and risks. Families
may be vulnerable to the emotional effects of marketing for cord blood
banking at the time of birth of a child and may look to their physicians for
advice. No accurate estimates exist of the likelihood of children to need
their own stored cord blood stem cells in the future. The range of available
estimates is from 1 in 1000 to more than I in 200 000.51 The potential for
children needing their own cord blood stem cells for future autologous(self)
use is con-troversial presently." There also is no evidence of the safety or
effectiveness of autologous(self) cord blood stem cell transplantation for
the treatment of malignant neoplasms. indeed, there is evidence
demonstrating the presence of DNA mutations in cord blood obtained from
children who subsequently develop leukemia. Thus, an autologous(self) cord
blood transplantation might even be contraindicated in the treatment of a
child who develops leukemia.
Cord blood has been shown to contain pluripotent stem cells that have the
potential to differentiate into nonhematopoietic tissue, such as cardiac,
neurologic, pancreatic, and skin tissue, in vitro. Extensive laboratory
research is taking place to explore the potential therapeutic benefit of
cord blood under these circum-stances. The results of this research will be
necessary to formulate future recommendations regarding autologous(self)
cord blood banking.
Initially, cord blood stem cell transplantation using allogenic(others)
umbilical cord blood was performed in relatively small children, because the
cell dose per weight of recipient was shown to be important., However, older
children, adolescents, and adults have benefited from unrelated
allogenic(others) umbilical cord blood transplantation . Because of the
relationship between cell dose per recipient weight and transplant outcome,
the number of cord blood cells needed for marrow reconstitution in older
children or young adults is much larger than that needed when cord blood is
used for transplantation in small children. Cord blood transplants using
multiple cryopreserved units from separate donors have been performed
successfully in adults, and the approach is currently under investigation as
a strategy to increase the dose of cells for transplantation in a single
recipient. Cord blood is collected in observance of good obstetric and
pediatric practice.
Although cord blood is currently considered discarded human material, it
should only be collected for banking with an institutional review
board-approved protocol and with signed informed consent from a parent.
Pertinent donor information communicated to the cord blood bank should be
kept confidential by the cord blood bank and used only to report important
medical information obtained during the cord blood collection, processing,
and screening process that is relevant to the safety of the donor and
family. If cord blood was collected from a newborn who subsequently
developed a genetic, immunologic, or malignant neoplastic disorder, parents
should notify the cord blood bank so that the unit is not used for
transplantation. All cord blood units banked for potential use should be
tested for infectious diseases, similar to those tested in a blood bank, and
for hereditary hematologic diseases. The informed consent must contain
information pertaining to what tests are to be performed on the cord blood
and how the parents will be informed if test results are abnormal.
Pediatricians should be aware that legal cases relating to the duty of a
physician to warn parents about the risks of inheriting a genetic disease
are new and untested. Pediatricians should remain vigilant, because future
cases may define who has a legal duty to notify parents about genetic
abnormalities identified during cord blood testing. Informed consent should
be obtained before the onset of active labor and before cord blood
collection.
RECOMMENDATIONS
Cord blood transplantation has been shown to be curative in patients with
a variety of serious diseases. Physicians should be familiar with the
rationale for cord blood banking and with the types of cord blood-banking
programs available. Physicians consulted by prospective parents about cord
blood banking can provide the following information:
1. Cord blood donation should be discouraged when cord blood stored in a
bank is to be directed for later personal or family use, because most
conditions that might be helped by cord blood stem cells already exist in
the infant's cord blood (ie, premalignant changes in stem cells). Physicians
should be aware of the unsubstantiated claims of private cord blood banks
made to future parents that promise to insure infants or family members
against serious illnesses in the future by use of the stem cells contained
in cord blood. Although not standard of care, directed cord blood banking
should be encouraged when there is knowledge of a full sibling in the family
with a medical condition (malignant or genetic) that could potentially
benefit from cord blood transplantation.
2. Cord blood donation should be encouraged when the cord blood is stored
in a bank for public use. Parents should recognize that genetic (eg,
chromosomal abnormalities) and infectious disease testing is performed on
the cord blood and that if abnormalities are identified, they will be
notified. Parents should also be informed that the cord blood banked in a
public program may not be accessible for future private use.
3. Because there are no scientific data at the present time to support
autologous(self) cord blood banking and given the difficulty of making an
accurate estimate of the need for autologous(self) transplantation and the
ready availability of allogenic(others) transplantation, private storage of
cord blood as "biological insurance" should be discouraged. Cord blood banks
should comply with national accreditation standards developed by the
Foundation for the Accreditation of Cellular Therapy (FACT), the US Food and
Drug Administration (FDA), the Federal Trade Commission, and similar state
agencies.
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You can donate your baby’s cord blood for free to the
national cord blood bank to help other babies. And many other parents give
their baby’s cord blood for you to use if the need should arise. Here is
the web site that you can read up and get contact information to donate it.
