Cord blood banking and its implications for midwifery practice: time to review the evidence?
The full reference for this draft article is: Trotter S (2008). Cord blood banking and its implications for midwifery practice: time to review the evidence? Midirs Midwifery Digest 18: 2 159-164
Click on the links below to read sections of the article:
Abstract
As a midwife and mother, I investigated the possibility of collecting my sons’ cord blood in 1999. Back then information was harder to obtain. There was no public bank within easy reach and private collection was prohibitively expensive. This is no longer the case and more parents are seeking to collect Umbilical Cord Blood (UCB).
The first Bone Marrow Transplant (BMT) was carried out in 1956 (www.medhunters.com web article). The birth of the first baby conceived by in-vitro-fertilisation in 1978 (www.bbc.co.uk web article) caused a media storm and yet these procedures are now valued as part of health care options and undertaken on a regular basis. At their inception however, both procedures were expensive cutting edge treatments with little or no guarantee of success but the long term benefits for all concerned were deemed to be worthy of the considerable investment involved. It is my view that we should learn from such experiences and consider that the place for stem cell collection from cord blood through the use of cord blood banking services will follow a similar paradigm.
In recent years, advances within this field have progressed at a rate to silence the majority of critics. While Haematopoietic Stem Cells (HSC) have been used for research purposes since the early seventies, it is only in recent years that it has been possible to use them in ground breaking treatments for a wide variety of conditions.
This article traces the brief history of cord blood banking, offers explanations about why cord blood is unique and describes its use as a treatment for various conditions. National and international legislation in place to protect all parties will be documented and the differences between public and private banks explored.
The current guidance from professional bodies with regard to the use of UCB and the ethical implications for practice are discussed. Suggestions on how to develop new guidelines, acceptable to both parents and professionals are proposed alongside a review of the practical issues surrounding UCB collection and the potential for future therapies within this pioneering area of science.
Due to the many abbreviations; a glossary of terms is included which should act as a quick reference to those unfamiliar with this subject. There are also references to numerous website resources in the right hand column. [back to top]
Glossary of terms:
ASBMT - American Society for Blood and Marrow Transplantation
BMDW – Bone Marrow Donors Worldwide
BMT – Bone Marrow Transplant
CBB – Cord Blood Banks
EBMT – European group for Blood and Marrow Transplantation
FACT – Foundation for the Accreditation of Cellular Therapy
GLP – Good Laboratory Practices
GMP – Good Manufacturing Practices
GvHD – Graft Vs Host Disease
GvL – Graft Vs Leukaemia
HLA – Human Leucocyte Antigen
HTA - Human Tissue Authority
HSC - Haematopoietic stem cells
ISCT - The International Society for Cellular Therapy
JACIE - Joint Accreditation Committee – ISCT – EBMT
LCBB – London Cord Blood Bank
NBS – National Blood Service
PC – Progenitor Cells
PBSC – Peripheral Blood Stem Cells
TRM – Transplant related Mortality
TSC – True Stem Cells
UCB – Umbilical Cord Blood
UCBT – Umbilical Cord Blood transplant
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Cord blood – a brief history It was in the early nineteen seventies that Ende (1995) first observed that cord blood, like bone marrow, was a rich source of Haematopoietic Stem Cells HSCs. These are Master cells with the capacity to become any type of cell or tissue (pluripotent). Embryonic stem cells are known as True Stem Cells (TSC) in that they retain an unlimited capacity for self renewal whereas adult stem cells could be better described as Progenitor Cells (PC) as their capacity for unlimited renewal has not been conclusively demonstrated.
The four main sources of stem cells are: embryonic blood, peripheral blood, bone marrow and cord blood. Understandably, the use of embryos to harvest stem cells is highly emotive and while Bone Marrow Transplants and [cytokinine mobilised] Peripheral Blood Stem Cells (PBSC) work well, Umbilical Cord Blood Transplantation (UCBT) has been demonstrated to be equally useful (Arcese et al 2006).
The first successful UCBT was carried out in 1989 (Gluckman et al 2004) confirming UCB as an important and viable source of HSC. There have been thousands more successful transplants since then (for various reasons including malignancies of the blood in children and more recently adults). Where the use of cord blood has become common practice, the number of Cord Blood Banks (CBB) around the globe has continued to increase with the development of many centres of excellence. [back to top]
Why is cord blood so special?
In practice collecting cord blood is easy. There is no direct risk to mother or baby and less risk of the sample being infected. Cord blood can be stored for immediate use and shipped to any transplant centre in the world. The use of cord blood for transplant is associated with a reduced risk of Graft Vs Host Disease (GvHD). This is despite the fact that most UCBTs are less than perfectly matched with commonly 4-5/6 Human Leucocyte Antigen (HLA) A, B & DRBI antigens (a perfect match looked for when carrying out a BMT is a 6/6 HLA match).
This phenomenon is not fully understood but it is thought to be associated with the unique qualities of the cord blood HSCs which are known to be primitive in nature though fewer in number than those from other sources. However, in the presence of growth factors these immature cells are capable of significant proliferation which more than compensates for their relatively low yield within cord blood. After transplant there is a reduced cytokine release (immune response) which accounts for appreciably less severe cases of GvHD, while at the same time maintaining the protective Graft Vs Leukaemia (GvL) effect (Gluckman & Rocha 2005).
The only limiting factors for using UCB in adult transplantation are the overall low cell dose, a slower engraftment (leaving recipients more open to infection during the recovery period due to lower levels of platelets and neutrophils) and the fact that there is no possibility of going back to the donor for a second sample. However, results from worldwide transplantations using UCB have shown a drop in Transplant Related Morbidity (TRM) which is encouraging.
Cell dose is a major factor to the success of UCBT and the acceptable threshold for such transplants is 1.7 x 105 infused CD34+ (early cell protein) cells/KG³ or 2.5 x 107 cryopreserved nucleated cells/KG (Schoemans et al 2006). [back to top]
Types of cord blood donations
UCB can be used for the donor themselves - this is known as autologous directed, whereas a donation to a family member is known as allogeneic directed. Donations of UCB can be made through public facilities, sometimes known as altruistic or unrelated banks or private facilities, which are termed private or related (family) banks.
A more detailed comparison of the services offered and the strict regulation governing them is covered later in this article.
It has been speculated that the chances of needing to use a privately donated unit of UCB is 1:2700 by the time a child is 18 years old (Johnson 1997). However, this does not take into consideration the prospect of using the UCB for another family member, or for non-blood related diseases or regenerative therapies. [back to top]
Public banks (unrelated or altruistic donations)
Once ethical permission has been granted to establish a public cord blood bank, support from obstetricians and midwives, as well as effective communication with the departments involved is vital. Staff training and the careful selection of donors can then begin.
The overriding aim is to obtain samples of UCB as safely as possible using protocols that have been accredited and licensed by the relevant regulatory authorities to ensure the highest quality product is registered with the Bone Marrow Donors Worldwide (BMDW).
The recruitment of suitable donors is paramount and a stringent selection process should be implemented with informed consent of the donor being the main priority. Guidelines are in place to avoid confusing potential donors and reduce the possibility of commercial pressure during this process. Full consent and pre-collection blood testing is documented throughout and plans for the UCB collection (either ex-utero or in-utero) are made.
Due to the high cost involved with setting up a cord blood bank, it is important for it to be situated in an area where the birth rate is high and the ethnic mix of the population diverse. This allows the bank to source a variety of tissue types known to be hard to match from the general population. As this will involve the selection of many ethnic groups, effective communication is essential. Potential donors must be provided with relevant, up-to-date information in accessible formats to allow for informed choice during the selection process.
The London Cord Blood Bank (LCBB) was set up in 1996 and a paper charting its first 1000 collections was published in 1999 (Armitage et al). The procedures and policies in place here, including Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP), are testimony to the close co-operation with the UK National Blood Services (NBS online). This ensures the infrastructure is in place to comply with internationally set standards (see section on legislation).
Specially trained staff (not necessarily midwives) carry out the actual collection of cord blood which is currently limited to four London hospitals. There then follows processing, testing, tissue typing, registration, cryo-preservation and storage of UCB units ready for use by transplant centres throughout the world (Warwick 2004). [back to top]
Private cord blood banks (related, family or directed donations)
Private Cord Blood Banks (CBB) provide the facilities for parents to collect directed UCB donations meant for personal use by the donor or their family members. A family with a pre-existing genetic disorder that has the potential to be treated with HSC therapy may also choose a private CBB. A public CBB may also be willing to regard these as ‘special’ cases. However, the most likely reason for individuals to collect their UCB is for ‘insurance related purposes’ (e.g. the? Potential to treat childhood leukaemia, should this occur). As research continues to highlight a diversity of uses for HSC from UCB more people will consider this simple and non-invasive technique with its associated potential for long-term benefit. At present there are more than 70 diseases reported to have been treated with the help of SC therapies (Harris & Goldman 2004) but it is not always made clear that this is predominantly through the allogeneic and not analogous use of UCB.
In the UK there are nine private CBBs (Verter 2007), although only five store their UCB ‘units’ in the UK. If a parent wishes to collect cord blood from their baby’s placenta using the services of a private CBB, it is their responsibility to organise for the collection to be carried out by a suitably qualified health professional.
The Royal College of Obstetricians and Gynaecologists’ (RCOG) and the Royal College of Midwives’ (RCM) current position [see UK Position papers in part two] can sometimes mean it is not possible to accommodate parents’ wishes. One of the reasons for writing this article is to increase knowledge about the range of services available and their purpose and to stimulate debate on the introduction of specific guidelines within each health authority to clarify the situation at a local level.
Collection aside, the fact that private banks do not usually make their UCB units available for public use by transplant centres means that very few people have the potential to benefit from this resource.
A recent innovative practice by one of the newest privately owned banks, Virgin Health Bank Ltd, might be the answer to critics of such banks. Virgin Health Bank Ltd holds 20% of the original UCB donation in storage for the donor family, the remaining 80% is made available (free of charge) to the BMDW. At present transplant centres pay between £10,000 and £15 000 for each unit of UCB. Virgin Health Bank’s groundbreaking initiative could pave the way for similar projects to be set up, increasing the collection of UCB which ultimately has the potential to help everyone.
Although the family paying for the collection and storage of their UCB only have guaranteed access to 20% of their samples, it is expected that this will still be extremely useful. Morally this remains a highly acceptable option when you take into account the latest techniques to expand cell count (maintaining the ability to treat a family member) alongside the fact that retrieval is more likely to be associated with regenerative therapies.
There is no doubt that continued research into this expanding area of science will uncover new and exciting ways to manipulate stem cells for the good of public health.
Co-operation between public and private banks is essential and open dialogue about initiatives to increase the availability of UCB units will be of benefit to all concerned. Unused samples could be offered back to the public registries after a period of five, 10 or 15 years in return for discounts on storage. Division of samples is also an option as the aforementioned techniques (to better utilise UCB) become established. [back to top]
Legislation of public and private banks
While it is not vital for midwives to understand the legislation in place to regulate public and private CBBs, it may be reassuring to see how robust the regulations are and how they came to be:
1974
- In 1974 the European group for Blood and Marrow Transplantation (EBMT) was set up to monitor and research clinical bone marrow transplantation. This now includes all aspects associated with stem cells from any donor source. Members meet to share experiences and working parties, each headed by a chair person, are involved in research based on their specific expertise. There are currently 11 working parties and the latest world-wide joint venture called AlloStem ( EBMT working parties online) has secured the largest ever grant (€8 million) from the European Commission (EC) for an immunotherapy programme. This exciting programme aims to significantly increase the survival rates for leukaemia sufferers by developing new strategies to reduce the risk of GvHD, generate new anti-tumour immune responses and protect against opportunistic infections.
Their registry of CBBs known as Eurocord now works closely with NETCORD (see below).
1992 - The International Society for Cellular Therapy (ISCT) was set up as a professional organisation for those working in the field of cell based research as a forum for the communication, training and development of standardised technology. Membership is over 1100 worldwide.
1996
- In 1996 the Foundation for the Accreditation of Cellular Therapy (FACT) was founded as a non-profit organisation, in association with ISCT and the American Society for Blood and Marrow Transplantation (ASBMT) for the purposes of voluntary inspection and accreditation in the field of SC therapy. The first edition of the ‘FACT Standards’ was published in 1996 with inspections of participating applicants from 1997. These standards are now accepted as the template for other organisations in this field.
1998 - The Joint Accreditation Committee – ISCT – EBMT (JACIE) was established in collaboration with FACT to provide a body for the purposes of assessment and accreditation within a set of internationally agreed standards of excellence.
More recently FACT, co-operating with NETCORD (www.netcord.org ) exists to revise blood bank accreditation standards. NETCORD is now an international consortium of 14 leading public cord blood banks. Standards were finalised in 2006 and banks are gradually being added to the new system. Presently, only public banks and private banks using dedicated professionals to collect their cord blood specimens are eligible. All cord blood banks must be inspected and accredited by the relevant competent authority. In Europe, this is governed by the European Union through their European Tissues and Cells Directive (Directive 2004/23/EC) with UK banks being licensed by the Human Tissue Authority (HTA). In the US this is under the legislation of the Food and Drugs Administration (FDA). [back to top]
UCB – collection and storage
UCB can be collected either in-utero (before separation of the placenta) or ex-utero (following complete expulsion of the placenta). Both methods are straightforward to perform following appropriate training (similar to taking cord blood for routine samples if a woman is rhesus negative). It has been postulated that in-utero collection is quicker (two to five minutes against 10 to 15 minutes for ex-utero collection), easier to perform and results in a larger volume of collected blood (Lasky et al 2002) while others believe there is no significant difference (Warwick 2004). Whichever method is used, infection control is vital to prevent contamination from bacteria, fungi, maternal blood or secretions.
Fastidious pre-cleaning of the cord is carried out prior to cannulation. Passive blood flow into specialised bags containing anticoagulant usually results in an average volume of 60 to 80mls.
Once collected, the cord blood is processed in a closed system to remove the red blood cells and plasma, leaving a buffy coat (white blood cells and platelets left after separation process) of 20 to 30mls maintaining the quality and quantity of stem/proginator cells.
Routine testing prior to and after cryopreservation (similar to testing for routine blood donors) is carried out using the waste portion of the separated sample and includes: Full Blood Count (FBC), Human Leucocyte Antigen (HLA) antigens, CD34+ (early cell protein), nucleated cells, infection and microbiology screening.
Documentation and registration of units for transplantation is completed prior to controlled cryopreservation under automated conditions. In the UK specialised bags are used to avoid any chance of cross contamination. Laboratory techniques will evolve, but ultimately the aim of collection and storage should be to ensure the cell viability of all samples while they remain contamination free. Viability has been proven to be around 15 to 20 years (Broxmeyer et al 2003) but time will tell if this could be extended. [back to top]
Use of UCB in children and adults
A recent paper by Hayani et al (2007) published the first documented account of a successful autologous Umbilical Cord Blood Transplantation (UCBT). The child is still in remission two years following transplant. This suggests that as a form of treatment, though realistic and effective, it remains rare.
While the successful use of UCB for the treatment of children has been well documented, (Gluckman & Rocha 2005, Martin et al 2006) its use for adult treatments is still in the development phase. This is mainly due to the reduced cell volume of UCB units for transplantation, but new and exciting innovations are being pioneered to overcome this challenge (Rocha et al 2004). A review of UCBT in adults carried out from 2001 to 2005 was cautiously optimistic. The authors were confident that the near future would ‘show a rapid evolution of the transplant modality’ (Schoemans et al 2006).
UCB units are by nature individual. A simple answer to reduced cell volume would be to double the dose (see below). [back to top]
Nonmyeloblative Stem cell Transplantation (NST)
This double-dosing is being incorporated by scientists at the University of Minnesota: using two units of 4-6/6 HLA matched grafts (a perfect match looked for when carrying out a Bone Marrow Transplant [BMT] is a 6/6 HLA match). Results have been promising (Brunstein & Wagner 2006) with a reduced rate of Transplant Related Morbidity (TRM). NST is a reduced preoperative regimen of chemotherapy for patients ineligible for myeloblative treatment. This method works on the premise that UCB, as an alternative source of Haematopoietic Stem Cells (HSC), enables the Graft vs. Host Disease (GvHD) and Graft vs. Leukaemia (GvL) effect (known to be lower following UCBT) to boost the chances of engraftment even with less pre-treatment. First trialled on dogs (Storb et al 1997) subsequent studies on humans have proved encouraging and more trials are planned. [back to top]
Ex-vivo Expansion Culture
UCB stem cells have been shown to grow faster (as they do in embryonic life) in conditions of near-zero gravity. This pre-treatment expansion of cells allows cord blood units to be manipulated to achieve cell doses high enough for adult transplantation. This technique is still in its infancy and results are not conclusive. However, pre-clinical data suggests that UCB progenitor cells possess superior engraftment capacity than Bone Marrow (BM) and Peripheral Blood Stem Cells (PBSC) [Schoemans et al 2006]. More trials are needed. [back to top]
Intra Bone Marrow Injection (IBMI)
The injection of HSC directly into the bone marrow is being considered as another possible use of UCB with the potential to improve ‘homing’ after transplantation. Mesenchymal Stem Cells (MSC) facilitate engraftment by producing growth factors and cytokines while T Regulatory (Treg) cells help prevent autoimmunity. Treatment involving the above are further examples of how post transplantation complications could be treated using UCB as a source for these cells (Brunstein & Wagner 2006). [back to top]
Royal College of Midwives (RCM) and Royal College of Obstetricians and Gynaecologists (RCOG) – Position Papers in the UK
RCM
The last position paper on CBB from the RCM was issued in 2002 (RCM 2002). This advice remained unchanged following a press release in 2007 (RCM 2007). While it supports the collection of UCB when medically indicated, it does not support the commercial (private) collection of UCB. Concerns include:
• the possibility of future litigation due to problems during collection, storage and transportation (disclaimers are now in place to address these issues)
• the potential for increased risk of needle stick injury (already a calculated risk during the intrapartum period, this additional procedure could be seen to increase exposure)
• the need for more evidence to demonstrate real value of the collection of UCB (there is considerably more evidence today than when this position paper was published)
• the possibility of disruption around the time of delivery (this could be addressed by the introduction of standard guidelines implemented within each maternity unit to safeguard mother and baby)
• the need for wider debate in the NHS on the ethical, legal and safety implications of introducing commercial initiatives (National Institute for Clinical Excellence [NICE] guidelines could also be developed to take account of these issues)
RCOG
The Scientific Advisory Committee for the RCOG recently updated their opinion paper on CBBs (RCOG 2006).
Advice and recommendations include:
• Donations from at risk families are acceptable through CBB
• Future non-HSC use remains speculative but it is understandable for some parents to avail themselves of commercial services offered. This must be seen within the context of resources at each maternity unit
• Each NHS unit should have its own policy in place to deal with public or private collections of UCB. This information must be made available to parents at an early stage before they incur financial obligations with commercial banks
• There should be no change to usual management of the third stage
• Collection should be made from the ex-utero separated placenta by a trained third party (not necessarily a midwife) using methods and facilities in-line with the European Directive (Directive 2004/23/EC).
• Collection should not be made if the attending clinician believes it to be contra-indicated
• Improved funding of public CBB should be expedited for cases where true need has been established
• More research is needed into third stage practices [back to top]
Discussion
The field of UCB donation is relatively new and it raises emotive ethical, medical, scientific and social issues. For practising midwives, their prime consideration must always be to provide optimal care for the mother and her baby. The Midwives Rules (NMC 2004) states:
“Except in an emergency, a practising midwife shall not provide any care or undertake any treatment which she has not been trained to give”.
The collection of UCB during or after the third stage of labour could be complicated by a series of factors including: multiple birth, prematurity, the cord around the neck, risk of post partum haemorrhage or emergency caesarean section. Furthermore, it has the potential to disrupt the initial period of bonding when skin-to-skin contact and early breastfeeding should be allowed to progress unhindered.
Controversy surrounds the timing of cord clamping and where possible the facilitation of a physiological third stage should be encouraged. Whilst support for delayed cord clamping is growing (Weeks 2007), it is worth noting that a recent systematic review comparing early or late cutting of the cord demonstrated no clear evidence either way for full-term healthy neonates (Lainez et al 2005).
Ethical considerations for debate include:
• Who owns the UCB?
• Who can authorise its release?
• Will the UCB ever be required by the donor?
• Does irresponsible marketing by commercial CBBs coerce parents into signing up for this service or could this be seen as raising awareness of public banks?
The debates will continue with answers often less than straightforward, but one fact remains: the collection of UCB is here to stay.
As clinicians, we have a responsibility to make ourselves aware of the latest research behind such new technologies. Only then can we hope to provide our clients with the authoritative information to enable them to make an informed decision. Therefore it is important to have a full understanding of the extent that these innovations might impact on our practice. It is also important to take into account that practice incorporates care, and this might require us to make changes in order to provide this where it is the choice of the mother .
Education is central to this and we must be seen to be working in collaboration with our peers to affect a set of guidelines that are satisfactory for all concerned. [back to top]
Conclusion
A wealth of literature is available on the subject of UCB banking and its sequel. However the implications for midwives, especially in relation to their unique role during the intrapartum period, are obvious. This article was written to highlight the various issues relating to this complex subject in a bid to generate discussion on how we can embrace its associated possibilities. As well as providing the potential for vital curative samples for the donor family, UCB banking has the potential to benefit everyone.
Critics of private banks may claim that donations are being denied to deserving cases. It could equally be argued that an increased use of autologous UCB from such banks could actually reduce the demand on overstretched public CBBs.
In addition it could be said that the revenue spent by private CBBs marketing their services raises public awareness of UCB banking and has the potential to increase public donations.
Obstetricians and midwives are the leading care givers during the antenatal period and more specifically around the time of birth (when UCB is collected). Hence, clear and ongoing dialogue should take place between the RCM, RCOG and NICE to develop and establish standardised guidelines relating to the collection of UCB (by a third party) and associated procedures. Further discussions on who the ‘third party’ could be and how they are trained needs to be explored.
Following such discussions at national level, local Heads of Midwifery (HoM) should seize the initiative by implementing the resulting guidelines within each maternity unit. Subsequently, when enquiries are received (as is already the case) there will be a structured protocol in place to provide parents with the answers they deserve. [back to top]
References:
Arcese W, Rocha V, Labopin M et al (2006). Unrelated cord blood
transplants in adults with heamatologic malignancies. Haematological/ the haematology journal, 91(2): 223-230.
Armitage S, Warwick R, Fehily et al (1999).Cord blood banking in London: the first 1000 collections. Bone Marrow Transplantation, 24: 139-145
Broxmeyer H, Srour EF, Hangoc G et al (2003). High efficiency recovery of functional haematopoietic proginator stem cells from human cord blood cryopreserved for 15 years. Proc. Natl Acad Sc. USA, 100:645-650.
Brunstein CG & Wagner JE (2006). Umbilical cord blood transplantation and banking. Annu. Rev Med, 57:403-17.
Directive 2004/23/EC of the European Parliament and of the council of 31st March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. Official journal of the European Union 7.4. (http://europa.eu.int/eur-lex/ pri/en/oj/dat/2004/l_102/l_10220040407en00480058.pdf)
EMBT Working Parties: Allostem:http://www.ebmt.org/5WorkingParties/IBWP/wparties-ib4.htm (accessed on 26/08/07)
Ende M (1995). History of umbilical cord blood transplantation. Lancet, 346:1161.
Gluckman E, Rocha V, Arcese W et al (2004). Factors associated with outcome of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol, 32:397-407.
Gluckman E & Rocha V (2005). History of the clinical use of umbilical cord blood aematopoietic cells. Cytotherapy, 7(3):219-27.
Harris DT & Goldman S (2004). Cord blood banking: state of the science. Contemporary Pediatrics (July Supplement): 3-11.
Johnson FL (1997). Placental blood transplantation and autologous banking – caveat emptor. Journal of Pediatric haematology & oncology, 19(3): 183-86.
Hayani A, Lampeter E, Viswanantha D et al (2007). First report of autologous cord blood transplantation in the treatment of a child with leukaemia. Pediatrics, 119(1):296-300.
Lainez VB, Bergel AE, Calferata Thompson ML, Belizan Chiesa JM (2005). Early or late umbilical cord clamping? A systematic review of the literature. An Pediatr (Barc) 63: 14-21(in Spanish).
Lasky LC, Lane TA, Miller JP et al (2002). In utero & ex-utero cord blood collection: which is better? Transfusion, 42: 1246-48.
Martin P, Carter S, Kernan N et al (2006). Results of cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biology of blood and marrow transplantation, 12:184-94.
National Blood Services: Cord blood banking. www.blood.co.uk/nhscordblood/ (accessed on 28/08/07)
Nursing and Midwifery Council. (2004) Midwives Rules and Standards. NMC: London. P 16(6:2).
Rocha V, Labopin M, Sanz G et al (2004). Transplants of umbilical cord blood or bone marrow from unrelated donors in adults with acute leukaemia. The New England journal of Medicine, 351(22):2276-85
Royal College of Midwives (2002). Commercial cord blood collection – Guidance paper 1a and Position statement No: 1. RCM Journal, 5(12):422-4.
Royal College of Obstetricians and gynaecologists (2006). Umbilical cord blood banking – Scientific Advisory committee Opinion Paper 2, revised June 2006. RCOG, London.
Schoemans H, Theunissen K, Maertens J et al (2006). Adult umbilical cord blood transplantation: a comprehensive review. Bone Marrow Transplantation, 38: 83-93.
Storb R, Yu C, Wagner JL et al (1997). Stable mixed haematopoietic chimerism in DLA – identical littermate dogs given sub lethal total body irradiation before and pharmacological immunosuppression after bone marrow transplantation. Blood, 89:3048-54.
Verter F (2007). A parents guide to cord blood banks: http://parentsguidecordblood.org/content/usa/banklists/listeurope.shtml?navid=16#king Accessed on 26th August 2007.
Warwick R & Armitage S (2004). Cord blood banking. Best practice & research Clinical Obstetrics and Gynaecology, 18(6): 995-1011.
Web articles:
http://www.medhunters.com/printArticle/transplantTimelineBMT.html
http://news.bbc.co.uk/onthisday/hi/dates/stories/july/25/newsid_2499000/2499411.stm
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