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Volunteer cord blood banking and transplantation
Hilary Blacklock, Lochie Teague, Nigel Patton, Peter
Browett
Cord blood banking is a prerequisite for cord blood
transplantation,1 which is used increasingly
(mainly in children) to treat serious diseases of the bone marrow, blood, and
immune system.
Excellent outcomes are achieved using family or unrelated
donations similar to allogeneic haemopoietic transplants from other sources
(bone marrow or peripheral blood stem
cells).2,3 Placental blood has advantages;
these include easy and prompt access, the absence of risk in the donation
procedure (mother and baby), the need for less rigorous HLA-matching (improving
the odds of matching for minority populations under-represented on adult donor
registries), and reduced risks from transmitted viruses and graft versus host
disease.1–3
Trained personnel are needed to collect >80 ml of
placental blood for banking—at least 2 x 107
nucleated cells/kg recipient’s weight are necessary in allogeneic
transplantation to reduce the risk of rejection and disease relapse; the more
the better.4 Cord blood cells are viable after
15 years of storage5—however it is
predicted that these will survive longer if kept under the right conditions.
The success of paediatric cord blood transplantation has
lead to the development of at least 37 volunteer cord blood banks in 21
countries, funded to varying degrees by governments and/or public donations.
Accredited registries must comply to minimum standards and codes of conduct of
their umbrella organisations, the Foundation for the Accreditation of Cellular
Therapies and NETCORD. In this country, these are accessed for patients by the
government-funded New Zealand Bone Marrow Donor Registry
(NZBMDR)6 through Bone Marrow Donors Worldwide
(BMDW).
In recent years, New Zealand patients have been treated
using cord blood donations imported from the USA, Australia, Italy, Spain, and
Japan. The Ministry of Health (MoH) and the NZ Blood Service (NZBS) have been
reviewing the need for a national volunteer Cord Blood Bank since a proposal was
submitted by the Leukaemia and Blood Foundation of NZ in 1999 (L
Teague)–an outcome is still awaited. One aim was to increase potential
donors for Maori and Pacific Islanders, children of mixed ancestry, and ethnic
minorities who do not have a family donor. Such patients are less likely than
Europeans to have a matched donor on the international bone marrow and cord
registries, which allow access to more than 9 million marrow and cord donors
currently. However, the recruitment of more than 7,000 healthy Maori and Pacific
Island volunteer adults by the NZBMDR has improved the availability of unrelated
donors for Polynesian patients.
Some cord blood units contain insufficient cells to treat an
adult. Thus cord blood transplantation has only been used in a small number of
adults with high-risk disease lacking a histocompatible family or unrelated
donor. There is ongoing research using multiple cord blood donations for one
adult recipient (producing sustained donor
chimerism),7 and
ex-vivo cell expansion devices to
increase the stem cell dose.8 Recent studies
conclude that HLA-mismatched cord blood should be considered an acceptable
source of stem-cells for adult transplantation in the absence of an HLA-matched
adult donor.9 NZ adult patients with of
relatively unique mixed ancestry are sometimes impossible to match locally or
from the BMDW, and in those instances rapid access to single or multiple mildly
incompatible cord units would be an advantage.
Some patients have received a cord blood transplant from a
healthy sibling (not affected by the same condition) usually born after the
initial diagnosis. This includes children with familial disorders (such as
thalassaemia, immunodeficiency, and inborn errors of metabolism) as well as
acquired serious conditions (such as aplastic anaemia and acute leukaemia). This
clinical need has lead to the development of sibling-donor cord blood
programmes.10 Also, there are increasing
situations where pre-implantation genetic diagnosis or HLA typing is performed
to produce healthy histocompatible offspring (designer babies) as potential
donors for affected siblings.11
In genetic blood disorders, the patient’s own stem
cells are usually unsuitable for transplant. This is also the situation in a
number of acquired diseases including some cases of leukaemia where the
malignant cells may be present in the blood in the neonatal period, even though
the condition is not apparent for months or
years.12 It is also relevant that many children
with serious stem cell defects can be successfully treated without stem cell
transplantation—e.g. more than 75% of children with acute lymphoblastic
leukaemia are cured using modern
chemotherapy.13
New
Zealand legislation allows umbilical cord blood to be used only to treat the
child from whom the stem cells were harvested. However, parents can apply to the
MoH for an individual exemption to this rule. The current MoH/NZBS review should
include guidelines to store cord blood from healthy children born into a family
with a specific medical need requiring
transplant,10 with careful attention to
collection and storage standards as well as ethical issues such as the ownership
of the cells.
Currently, in New Zealand and internationally, storage of
cord blood for future use of that baby is done by several private for-profit
cord blood banks for a collection fee and an ongoing annual cost. Although cord
blood banks are an option for those who can afford them, the probability that a
child will use their own banked cord blood at the current time is extremely low.
The most active United States (US) private registry has stated (in September
2005) that it has provided stem cells for 34 clients (mostly siblings of donors)
from 250,000 units stored.14
Because of the proliferation of private cord blood banks in
the US of varying standards, the American Academy of Pediatrics issued the
following statement:
Given the difficulty of
making an accurate estimate of the need for autologous transplantation and the
ready availability of allogeneic transplantation, private storage of cord blood
as "biological insurance" is unwise. However banking should be considered if
there is a family member with a current or potential need to undergo stem cell
transplantation"15
Controversies related to private cord banks are further
discussed in the accompanying article by Sullivan et al. (Sullivan M, Browett P,
Patton N. Private umbilical cord blood banking: a biological insurance of
dubious future benefit! URL: http://www.nzma.org.nz/journal/118-1208/1260).
Private cord blood storage is also stimulated by research
that stem cells can potentially grow into other tissues such as heart muscle and
neurones.16 Such treatment options remain
experimental at present—but, in the future, stem cells from a
patient’s own blood or bone marrow and/or unrelated cord blood might be
appropriate treatments. The field of stem cell research and transplantation is
rapidly changing and health policy must consider how the medical demand for cord
blood may evolve in the future.
Acknowledgement: The
NZBMDR is administered by the NZ Leukaemia and Blood Foundation of NZ (URL: http://www.leukaemia.org.nz).
Author information:
Hilary A Blacklock, Haematologist, Middlemore Hospital, Otahuhu, Auckland (and
Medical Director, New Zealand Bone Marrow Donor Registry); Lochie Teague,
Paediatric Haematologist, Starship Hospital, Auckland; Nigel Patton,
Haematologist, Christchurch Hospital, Christchurch (and Chairman, New Zealand
Bone Marrow Transplant Study Group); Peter Browett, Professor of Pathology,
School of Medicine, University of Auckland, Auckland (and President, New Zealand
Branch of HSANZ)
Correspondence:
Hilary A Blacklock, Department of Haematology, Middlemore Hospital, Private Bag
93311, Otahuhu, Auckland. Fax: (09) 270 4753; email: Hblacklock@middlemore.co.nz
References:
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