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Amended version January 2009

Cord blood banking in the UK

An international comparison of policy and practice

Ingeborg Meijer Madeleine Knight Pauline Mattson Bastian Mostert Paul Simmonds Wieneke Vullings

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Table of contents

1. Introduction 1

1.1 Background 1

1.2 Study objectives 1

1.3 Scope of the assignment 1

1.4 Main report and Annex 2

2. Executive Summary 3

2.1 Recommendations 5

3. Stem cells from cord blood 7

3.1 Stem cells and umbilical cord blood 7

3.2 Allogeneic and autologous transplantation 7

4. Cord blood collection, banking and use in the UK 9

4.1 Policy 9 4.2 Collection 10 4.3 Storage/banking 15 4.4 Use 20 4.5 Cost 25 4.6 Summary of UK review 26

5. International comparison of UK policy and practice 28

5.1 Benchmarking UK with selected comparator countries 28

5.2 Benchmark data from international organisations 35

6. Conclusions & recommendations 37

6.1 Conclusions in the context of the UK & benchmark data 37

6.2 Issues discussed at the workshop 39

6.3 Recommendations 40

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Table of figures

Figure 1 Stakeholders in cord blood collection 10

Figure 2 Collection of cord blood in the UK 15

Figure 3 Banking of cord blood 19

Figure 4 Organisation of use 22

Figure 5 Evolution in the geography of sourcing of cord blood units, national and

international (%) 22

Figure 6 Use of cord blood units 23

Figure 7 Cost of cord blood collection and banking 25

Figure 8 Cord blood banks in comparator countries 29

Figure 9 Blood sample units stored in the different countries 31

Figure 10 Cord blood use of all HPC transplants 32

Figure 11 Costs of collection and storage 33

Figure 12 Spanish Cost Model example 33

Figure 13 Private cord blood banks in comparator countries 34

Figure 14 Summary in numbers 35

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Cord blood banking in the UK: an international comparison

of policy and practice

1.

Introduction

1.1

Background

The UK is recognised as a world leader in the field of embryonic stem cell research. Government policy supports and encourages research using stem cells derived from all types of tissue, of embryonic, foetal or adult origin. In 2005, the UK Stem Cell Initiative (UKSCI) was asked to develop a comprehensive strategy to underpin the next decade of stem cell research in the UK.

The UKSCI report made 11 recommendations, which were all accepted by Government. The final UKSCI report stated that “the development of placental or umbilical cord stem cell banking services and therapies could be a potential area of interest”, which the report could not examine in sufficient detail.

1.2

Study objectives

As part of the continuing implementation and assessment of the UKSCI strategy for stem cell research, the Department of Health requested an investigation of policies and practices for placental and umbilical cord stem cell banking services, both in the UK and comparator countries.

The purpose of the review was to examine the effectiveness of the UK policy and practice on the collection, storage and use of umbilical cord blood (UCB). The analysis of the UK position was then used to benchmark six comparator countries, which included: Canada, China, France, Japan, Spain and the United States.

1.3

Scope of the assignment

In order to obtain an overview of the arrangements for UCB collection, storage and use in the UK, desk research and (telephone) interviews were conducted. This provided a starting point for (i) developing a model framework for benchmarking policies and practices in selected comparator countries, and (ii) cataloguing the outputs and achievements of the comparator countries in comparison with the UK situation. In line with the framework, case studies were performed to benchmark the countries with UK policies and practices. For each country, the case study provided an overview of the policies, practices and costs related to the collection, storage and use of umbilical cord blood in the respective countries. The international reviews focused on initiatives that are federal, public, private or a combination, and highlighted options and choices that have the potential to affect the effectiveness of cord blood banking. The research for each country was not limited to initiatives that were part of globally active (accrediting) organisations, but also included a comprehensive overview of the main initiatives mapped in a pragmatic way. However, the search for data relating to China and Japan was limited due to language barriers. Nonetheless, a sub-set of foreign data was arrived at, which we considered to be suitable to review the UK situation in light of international good practice, in order to provide lessons and insight for the Department of Health.

The benchmark data and the UK review analysis were presented in a stakeholder workshop that was held in London, on 28 May 2008, chaired by Ruth Warwick (Consultant Specialist for the NHS Blood and Transplant [NHSBT]). Representatives of all relevant stakeholder organisations were invited. The workshop included short expert introductions on collection, storage, use and research as well as extensive discussions with participants. Participants pointed at several issues at stake, which are

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summarised in the notes on the workshop and are included in the main report where appropriate.

Several sub questions are addressed in the following sections, including: • The role of NHS Trust’s, and the interaction between collectors and bankers • The number of cord blood samples needed in the UK to cover demand • The future use for autologous stem cell transplantation

• The role of public and private banking, both in the UK and internationally

1.4

Main report and Annex

The main report includes analysis of the implications of cord blood collection and storage, banking and use in the UK and comparison this situation with policies and practices in six selected comparator countries, with the report organised as follows: • Section 3 presents a very brief introduction to the issues surrounding stem cells

from cord blood

• Section 4 presents an overview of the UK situation

• Section 5 presents an analysis of the international comparison, discussing the UK situation in light of the position in the selected benchmark countries and where possible in the context of more global data from international organisations such as World Marrow Donor Association (WMDA) and NETCORD

• Section 6 presents our conclusions and recommendations

• In addition, the study has benefited from the organisation of a deliberative workshop in May 2008 involving representatives of the relevant stakeholders (the agenda, presentations, notes and list of delegates are appended)

The separate annex report contains the individual country benchmark reports, including a selection of data from international organisations. The notes on the workshop are also presented in the annex report.

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2.

Executive Summary

Umbilical cord blood banking has attracted growing worldwide interest in recent years, driven by an expansion in the therapeutic use of adult stem cells, the gathering promise of research extending application to a broader spectrum of health issues and the aspiration of many to pursue medical science in an area without the apparent moral hazard of work on embryonic stem cells.

A number of UK stakeholder groups are pressing the government to adopt a more active policy with respect to cord blood, reflecting international trends in cord blood collection and use.

The UK government has no specific, published policy regarding cord blood collection. In practice, policy makers, hospitals and healthcare professionals work within the context of the EU guidelines and the published advice of relevant professional bodies. The Royal College of Obstetricians and Gynaecologists’ position paper on umbilical cord blood banking (2006) is used widely as a key text and source of advice.

In July 2008, new rules came into force requiring the collection of cord blood to take place under licence from the Human Tissue Authority, which means cord blood can be collected only by people with specialist training and on premises that meet essential standards. This is the first time that collection of cord blood at birth has been regulated in the UK, and is intended to ensure the safety of mother and child while also seeking to make sure that samples collected are of a high quality.

It is against this backdrop that the UK government commissioned this international comparative analysis, to provide intelligence as to current policies, practices and trends as an input to its deliberations around the need to increase umbilical cord blood collection and use, and its potential practicable options.

This report presents a comparison of the UK situation with the policy and practice in six selected countries: Canada, China, France, Japan, Spain and the USA.

The annual number of cord blood samples used for transplantation proved difficult to establish due to different reporting methodologies, however we estimate usage falls in the range 50 (Canada) to 500 (Japan) transplants each year, with around 100 in the UK. In proportionate terms, this amounts to some 15-18% of all HPC transplants. Interviews suggest the number of cord blood transplants is increasing quite rapidly. Within the seven countries, national cord blood bank capacities vary widely, ranging from a low of around 2,000 samples for Canada to a high of over 200,000 samples for China. The UK national cord blood bank holds around 11,000 samples at present. The variability is in large part a reflection of population size, however there is a perception that the national capacities of Canada, France and the UK are sub-critical at present. Collection rates across the seven countries fall into two clusters, with Canada, Spain and the UK collecting proportionately fewer samples, at around 0.1% of births annually, while China, France, Japan and the USA are collecting proportionately more samples, at around 0.3% of births annually. The UK national blood bank collected more than 2,400 samples in 2007, a collection rate of around 0.13% of total births in the year.

There is a high attrition rate of samples between collection and banking in all countries. International figures suggest that typically 30-40% of collections result in a viable sample suitable for banking, where the UK achieves a much higher utilisation rate, of around 75%.

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Conventional wisdom suggests that 20,000 samples is the threshold for a medically and economically viable national cord blood bank. Canada, France and the UK each has rather fewer samples than this.

The UK national blood bank has made a public commitment to expand its repository over the next several years, building towards 20,000 samples.

The figure of 20,000 samples is a rule of thumb, rather than a definitive reference. Clearly, local populations and economic conditions differ from one country or region to the next, and in some cases are likely to have a significant bearing on the required size of national banks. Other parameters loom large too, from the quality of samples and storage to the range of uses to which the samples are put. Moreover, national banks can deliver the necessary medical service through means other than a singular bank, so for example international alliances or more commercial collaborations wherein samples are purchased at full economic cost on an ad hoc basis.

The UK national cord blood bank purchased 10 imported samples in 2007, at a cost of £170,000 or £17,000 for each sample.

International collaboration is an important feature of umbilical cord blood banking, due to the inherited nature of tissue type, and the need for vast numbers of stored samples in order to have adequate representation of ethnic minority groups.

The cost of (unrelated) cord blood collection and storage is not inconsiderable, with estimates of full economic costs ranging from £200 (China) to around £1,400 (UK). Annual unit storage costs range from around £35 (China) to £75 (UK, USA).

Oral presentation of the results of very recent research carried out for the Anthony Nolan Trust suggests that, with the application of more formal models and empirical data, the medical threshold is much higher than the 20,000 figure in widespread use, and possibly double that sample size. The research is to be published in due course, and the results, and the calculations, will be of great interest to policy makers and executives responsible for developing national blood banks.

International trends demonstrate an increase in the use of cord blood. In terms of haematopoietic stem cell (HPC) transplantation, there is an increase in both the absolute number of cord blood samples used for transplant, and the proportion of transplants using cord blood, in comparison with other sources of HPCs from bone marrow donations or peripheral blood stem cell donations.

A combination of factors is at work. Cord blood transplants demonstrate equivalent patient outcomes to bone marrow transplants, even when there is a lower degree of tissue type match, between the donor and patient. The advancement of new procedures utilising 2 or 3 cord blood samples for a single transplant has made cord blood transplant a credible treatment for adults as well as children, which has increased the size of the basic treatment population. Cord blood also provides an alternative source of HPCs for transplantation for patients of ethnic minority origin, who are underrepresented on bone marrow registries in the UK.

There is an increase in the use of cord blood for treatments other than HPC transplantation, particularly in the USA. Evidence shows successful use of cord blood in treating Type I Diabetes Mellitus, Hurler’s syndrome as well as for tissue repair. Clinical results suggest a much broader potential for the medical use of naïve immune cells and mesenchymal stem cells in cord blood. Future application might be wider still. Recent published research has claimed that a total of 85 conditions are treatable or supportable with cord blood. However, many of these potential uses of cord blood rely on the future development of mesenchymal stem cell expansion techniques. Collection is increasing around the world, blood banks are being launched and getting bigger, therapeutic use is expanding and extending and medical science holds out the promise that many more conditions might be treated or supported with cord-blood based therapies within 5-10 years, with equivalent or improved patient outcomes.

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The UK faces a number of challenges in considering the expansion of cord blood collection. These include the capacity of the system, the workload of professionals attending births and concerns over legal liability and early clamping of the umbilical cord, which is currently routine practice regardless of cord blood collection.

Currently, very few hospitals in the UK are committed to collecting cord blood at an institutional level, either for public or private cord blood banks. The private banks, for the most part, gain access to collection through private hospitals.

According to current rates of collection, banking and use in the UK, it will take another 6 years for the national cord blood bank to reach the target of 20,000 stored units. Due to attrition rates from collection to storage, the desired uplift of 9,000 units means that around 12,000 units would need to be collected across the period.

Assuming the UK cost base remains unchanged, where any scale economies are expected to be offset by inflation, the estimated cumulative additional costs of reaching 20,000 samples amount to around £17 million, or around £3 million a year, while annual storage costs might increase from around £0.9 million presently to £1.7 million by the end of the 6-year period. The annual additional costs of creating and maintaining a bank of 20,000 samples might be offset to some extent by a reduction in the number of imported units, which ranged from £0.1 million to £0.4 million a year. The option of using a public-private partnership might be considered as a practicable means by which to increase the rate of collection for the public bank, potentially permitting the UK to create a national bank of 20,000 samples within two to three years, as the private sector has substantially greater collection capacity than the public system. However, the UK has little experience of this model, and arriving at a workable solution would take time to devise, pilot and implement.

Further detailed analysis is required to assess the above issues including methods of collection, future need and health economics, in order to form relevant policies regarding cord blood collection.

2.1

Recommendations

Based on the results from the international review, and having heard the discussions on the several issues at stake at the workshop in London, we recommended the UK government consider:

• Developing an explicit national policy on cord blood, which amongst other things aims at increasing future rates of collection of cord blood for public banks

• Creating a high-level advisory committee to provide the minister and policy teams with advice on the detail of such a policy. The high-level group should consist of representatives of all parties in the chain of cord blood collection (inclusive of private parties), storage and use, to continue discussion on issues presented in this report and as a follow up to the workshop. A multi-stakeholder committee will ensure the advice is practicable, and should facilitate implementation and generally improve communication between all stakeholders in the community • Requesting the advisory committee to address each of the questions that were

raised at the end of the workshop

• Commissioning further research to obtain detailed information on public-private banking models, from a variety of perspectives and with fully worked through cost models, with examples sourced from various international practices

• Developing marketing guidelines for private cord blood companies, in order to prevent misleading information to the public

• Developing further insight into the place of cord blood stem cell research in relation to other stem cell research (cf. UKSCI’s recommendation)

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• Investigating the perceptions of British citizens on the issue of altruistic donation as opposed to private donation of cord blood, possibly making use of the public dialogue expertise and funds available to all government departments through the Sciencewise resource centre

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3.

Stem cells from cord blood

3.1

Stem cells and umbilical cord blood

Pluripotent stem cells are primitive stem cells capable of differentiation into multiple tissue types and cell lineages. This ability offers great potential for regenerative medicine. A specific type of stem cell found in humans, the haematopoietic progenitor cell (HPC) is a multipotent stem cell with the capacity to differentiate into the three classes of blood cells (erythroid, myeloid and lymphoid). Multipotent stem cells are committed stem cells with a restricted differentiation capacity.

Umbilical cord blood is rich in haematopoietic stem cells (HPCs), which are biologically similar to their adult counterparts. However umbilical cord blood appears to have advantages over HPCs obtained from bone marrow or peripheral blood, making it especially suited for haematopoietic stem cell transplantation. Umbilical cord blood is a richer source of both stem cells and early immune system cells that are immunologically more naive and have a greater potential to proliferate. In addition, umbilical cord blood carries a low potential for infectious disease transmission, and cord blood derived stem cells are biologically younger and have been subject to less genotoxic damage and epigenetic modification than their adult counterparts.

Umbilical cord blood also contains non-haematopoietic stem cells, most notably mesenchymal stem cells. Mesenchymal stem cells are another class of multipotent stem cell that is capable of differentiating into multiple lineages of structural and supporting tissues such as muscle, bone, and other soft tissue. Unlike bone marrow, mesenchymal stem cells are only present in low numbers in cord blood. They are also present in the Wharton’s Jelly, a thick layer surrounding the blood vessels in the umbilical cord.

3.2

Allogeneic and autologous transplantation

The potential of HPCs to reconstitute bone marrow and peripheral blood has been used for the treatment of patients with bone marrow damage from either chemotherapy or underlying haematological failure. Transplanting HPCs is effective for the treatment of for example leukaemia, selected genetic metabolic disorders and immunodeficiency’s and sickle cell anaemia. HPCs can be obtained from several sources including bone marrow, mobilised peripheral blood and umbilical cord blood collected from the placentas of recently delivered infants.

Transplantation is either allogeneic or autologous:

• Allogeneic stem cell transplantation is performed with stem cells that are collected from a related or unrelated donor, and transplanted into the patient to reconstitute bone marrow

• Autologous stem cell transplantation is performed with stem cells that are collected from the patient before treatment and are re-infused to reconstitute the bone marrow

An appropriate Human Leukocyte Antigen (HLA) match is important for all types of HPC transplantation regardless of the graft source. Individuals have three pairs of HLA-A, -B and DR antigens and a full tissue match is termed a 6/6 match. Matching is important: non-matching grafts are rejected by the immune system of the recipient. The inheritance pattern of the highly polymorphic HLA types means that the chance of finding a related fully matched donor is only 30%. For the remaining 70% of patients, an unrelated donor stem cell source must be found.

In an attempt to make HPCs more widely available to the large number of patients who do not have an HLA-identical sibling, large international volunteer adult (bone

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marrow and peripheral blood) donor registries were created in the 1980s. Today, more than 12 million registered, and tissue typed, adult donors are listed in more than 40 registries worldwide. In the UK, the British Bone Marrow Registry (BBMR) is taking care of the enrolment, testing/typing and registry of bone marrow donors1 (see

Box 1). Still, registries and transplant physicians face several challenges, such as: • Finding a full match for patients in many ethnic groups, especially those of mixed

race, remains a challenge. For many ethnic groups no more than 20-30% of patients can be matched, whereas a match can be found for up to 75% of patients of Western European origin

• Unavailability of some potential donors, even if an individual was identified in a registry on the basis of HLA match. Also, prolonged intervals between the time of a search request and the time of HPC acquisition (median time is greater than 4 months)

• Risks associated with bone marrow and peripheral blood donation. For bone marrow to be collected, the donor needs a full anaesthesia, which carries risks to the donor. Peripheral blood as a source of HPC depends on aphaeresis, which can take several hours and requires the prior stimulation by G-CSF (Granulocyte Colony-Stimulating Factor) of the donor. The risk-benefit profile of G-CSF stimulation is currently not entirely positive for donors

Large and accessible cord blood collections could resolve several of these issues. Given there are 130 million babies born each year worldwide, umbilical cord blood represents the largest potential source of stem cells for transplantation and regenerative medicine. Regenerative medicine is still in its infancy, however many expert scientists and doctors believe that its potential could bring many benefits with new treatments for certain illnesses and conditions.

Box 1 The British Bone Marrow Registry (BBMR)

The British Bone Marrow Registry (BBMR) is a voluntary bone marrow donor registry, which is run by the National Blood Service (NBS) on behalf of the other UK blood transfusion services. The BBMR works in conjunction with other blood transfusion services in the UK. Bone marrow donors are recruited from the blood donor population. In order to register, individuals must be between the ages of 18 and 49, provided no medical reasons, specified in detailed criteria, prevent them from donating. Where a bone marrow donor is required in the UK, searches will include the Anthony Nolan Trust register and the Welsh Bone Marrow Donor Registry. For patients under the age of 16 the search will also include the UK cord blood banks. The BBMR is part of the Bone Marrow Donors Worldwide (BMDW) register, an international internet-based organisation with more than 6 million registered donors. This way, where a donor is not found within the UK, the international registers can be searched for potential donors registered abroad.

Facilities wishing to use the BBMR must be accredited with an appropriate body such as the Foundation for the Accreditation of Haematopoietic Cell Therapy (FAHCT) or the Joint Accreditation Committee-ISCT & EBMT (JACIE) and an appropriate national or international transplant outcome organisation such as the National Marrow Donor program (NMDP) or the European Group for Blood and Marrow Transplantation (EBMT).

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4.

Cord blood collection, banking and use in the UK

4.1

Policy

Not many policies exist in relation to cord blood collection, except for regulations on the collection and storage process.

4.1.1

The Human Tissue Authority

The Human Tissue Authority (HTA) regulates umbilical cord blood collection in the UK. The HTA was set up under the Human Tissue Act 2004 (see Box 2) and is one of the UK’s competent authorities under the European Union Tissues and Cells Directive (EUTCD 2004/23/EC) (see Box 3).

Box 2 The Human Tissue Act

The Human Tissue Act (2004) set out a new legal framework for the storage and use of human tissue from the living and removal, storage and use of tissue and organs from the deceased. The HTA applies to England, Wales and Northern Ireland where it came into place on 1 September 2006. Similar regulations are in place in Scotland under the Human Tissue (Scotland) Act 2006. The HT Act replaces several previous acts, which covered these individual regions. The aim of the HT Act is to create a framework for donation that is clear and that patients, families and professionals can have confidence in.

The Human Tissue Authority (HTA) is responsible for giving advice on the HT Act and for ensuring that establishments performing these activities are regulated. In order to provide this support, the HTA issue guidance, codes of practice and licensing guidance for the professional sectors they regulate as well as carrying out inspections to ensure licence conditions are being met. The HTA issued two directives summarising the requirements of the Parent Directive and the First and Second Technical Directives of the EUTCD for establishments storing human tissues and cells for human application.

The HTA regulates the removal, storage, use and disposal of human bodies, organs and tissue from the living and deceased. The donor selection and evaluation, procurement, processing, testing and storage and distribution of umbilical cord blood are activities, which come under the Human Application sector of the HTA remit.

Box 3 The European Union Tissues and Cells Directive (EUTCD)

The EUTCD creates a common framework to ensure high standards in the procurement, testing, processing, storage, distribution and import or export of human tissues and cells across the European Union. The European Parliament Directive adopted the EUTCDs in 2004 and they came fully into force in the UK in April 2007. The Directive aims to ensure the safety and quality of tissues and cells used for human application.

Approximately a third of the European member states have fully incorporated the EUTCD. The UK has been in the vanguard of member states that have put into operational effect the requirements of the EUTCD.

The UK partially implemented the EUTCD via the Human Tissue Act 2004. Establishments intending to store human tissue or cells for human application should have been licensed for this activity from 7 April 2006 – including the storage of cord blood.

The EUTCD Parent Directive, published in March 2004, sets out the framework of the directive. There are two further detailed technical Directives that accompany the Parent Directive, which stipulate the standards for carrying out the activities of procurement, testing, processing, storage, distribution and import or export of tissues and cells across the European Union.

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The EUTCD came into force on 7 April 2006 throughout the European Union. The Directive was fully transposed into UK law via the Human Tissue (Quality and Safety for Human Application) Regulations on 5 July 2007.

The UK is at the forefront of complying with EU regulation. On 30 April 2008, the Human Tissue Authority announced new rules for the procurement of umbilical cord blood, which will be regulated for the first time in the UK in order to ensure the quality, safety and traceability of umbilical cord blood. The new rules stipulate that umbilical cord blood can only be procured by trained staff and only on premises that meet essential standards. The new rules came into place on 5 July 2008 and means that all premises that wish to carry out cord blood collection must apply for a licence to do so by that date – or, alternatively ensure that the procurement is taking place on behalf of a licensed establishment under a suitable third party agreement.

The licence, issued by the HTA, will ensure:

• “Staff have training in collecting cord blood, raising standards and making sure best possible quality of sample is taken

• Procedures which will help prevent any medical attention being drawn away from mother or child during collection

• A system is in place to make sure that the cord blood cells are traceable from collection to their use in treatments”

The HTA has developed a one-year interim licence fee for those organisations collecting cord blood, pending a broader licence fee review across all sectors. This fee is £2,900 and will be chargeable in the 2008/09 financial year.

4.2

Collection

Several stakeholders are involved in the collection of cord blood. These are depicted in Figure 1. The formal role and position of these stakeholders is shown in glossaries; the facts and figures concerning each of the stakeholders relevant for the review are presented here.

Figure 1 Stakeholders in cord blood collection

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4.2.1

Ethical considerations and clients perspective

Parents might wish to collect the cord blood of the baby they are expecting. Directed donation of cord blood is recommended for siblings born into a family where there is a known genetic disease amenable to HPC transplantation. If the cells are HLA-compatible, they may be used for the affected child. If the newborn child itself develops the disease, its own cord blood may potentially be used in the future. Directed cord blood collections would normally be initiated by the clinician caring for the potential recipient.

Directed donation in families at low risk of genetic disease is not encouraged. The likelihood that a child will ever need its own stem cells for treatment in their early years is very small – estimates range from 1 in 5,000 to 1 in 20,000. Children with an illness such as leukaemia are more likely to need healthy, donated cells and not their own.

In 2004, the European Group on Ethics in Science and New Technologies (EGE) issued an Opinion to the European Commission on the ethical aspects of umbilical cord banking, Opinion number 19 (see Box 4). At the time issued, most European countries did not have specific legislation on cord blood banking and practices varied in many cases.

Box 4 Opinion number 19 of the European Group on Ethics in Science and New Technologies (EGE), 16 March 2004

Several ethical principles are considered relevant to the issue of cord blood banking:

The principle of respect for human dignity and integrity, which asserts the principle of non-commercialisation of the human body

The principle of autonomy or the right to self-determination on the basis of full and correct information

The principles of justice and solidarity, as regards to fair access to healthcare services The principle of beneficence, or the obligation to do good, especially in the area of health care

The principle of non-maleficence, or the obligation not to cause harm, including the obligation to protect vulnerable groups and individuals, to respect privacy and confidentiality

The principle of proportionality, which implies a balance between means and objectives.2

The key ethical issues that apply to cord blood banking are those that apply to any tissue bank: body integrity, respect of privacy and confidentiality of data, promotion of solidarity, fairness of access to healthcare and information and consent of the donors.

In respect to umbilical cord banking EGE Opinion 11 states that “the information provided to the woman or to the couple must clearly explain these prospective new treatments, but stress that they are still very much at the experimental stage” and goes on to say that “in principle, tissue bank activities should be reserved to public health institutions or non-profit making organisations” but “tissue banks set up by industry should be subject to the same licensing and monitoring requirements as non-commercial operators”.3

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The EGE expressed some specific concerns about cord blood banking for potential future autologous use, which include:

• Altruistic donations versus for-profit collection reflecting the paradigm shift from a form of social cohesion and solidarity to services that are paid for by parents, may call into question issues of trust

• Accuracy of information to potential customers

• The risk of bankruptcy for long-term storage facilities offered by banks

• Competition between private banks and public banks for potential donations, and the potential effect on attaining the greatest possible diversity of cord blood units • Fairness of access to healthcare if the potential use of autologous stem cells is

realised; in that case patients who lack stored cord blood would be at a disadvantage

On the other hand, it is argued that the child (and by extension his/her parents) owns his/her umbilical cord blood, and that all pregnant women should be made aware of the option of cord blood collection/banking, according to the Human Rights Law. In the USA, the American Medical Association is positive about doctors encouraging women willing to donate the cord blood of their babies to public cord blood banks. Following this line of reasoning, hospital trusts are said to put themselves at legal liability if refusing to help with cord blood collection.

4.2.2

The professionals and hospitals

Cord blood collection needs to take place just after delivery of an infant, in or close to the delivery unit in a maternity ward of a public (NHS Trust) or private hospital. Collection of cord blood requires the cooperation of obstetricians and midwifes, and there should be no conflict of interest between the care of the mother and baby and cord blood collection. Ideally, after clamping the umbilical cord, cord blood is collected aseptically by trained staff. Antenatal written informed consent is given by the mother, either to store and use the cord blood for any patient in a public cord blood bank, or to store it in a private (family) bank for the exclusive use of the family. A considerable logistical burden is imposed on the obstetrician, the midwife and the hospital involved in a request for (personal) umbilical cord blood collection and storage. The consent procedure and associated paperwork put an additional workload on midwifery staff, which is usually not paid for.

As a response to requests from patients and professionals, a Scientific Committee to the Royal College of Obstetricians prepared and published a policy paper on the collection of cord blood. The Royal College of Midwives responded with a position paper (see Boxes 5 and 6). Essentially, both organisations acknowledge the need for public and altruistic cord blood collection albeit under stringent conditions. Both organisations however reject the medical need for autologous, cord blood collection, as they currently see no evidence in research supporting any added value to be gained from commercial banking. Most professionals refer to these position papers when asked about cord blood collection.

2 The European Group on Ethics in Science and New Technologies (EGE) is an independent

group of 15 experts appointed by the European Commission, which considers the ethical dimensions of science and technology associated with Commission legislation and policies on an ad hoc basis. It issued a full Opinion on the ethical aspects of umbilical cord blood banking, Opinion 19, 16 March 2004.

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Box 5 The Royal College of Obstetricians and Gynaecologists (RCOG)

Use of HPC obtained from umbilical cord blood has become an established alternative to bone marrow transplantation, especially in haematological, immunological and metabolic storage disorders in children and young adults. Storage of cord blood for therapeutic purposes will require a licence from the HTA under terms of the Human Tissue Act (2008):

• Collection of non-directed donations and directed donations for at-risk families are

acceptable procedures through established public sector cord blood banks. There is still insufficient evidence to recommend directed commercial cord blood collection and stem-cell storage in low-risk families.

• Future non-haematopoietic stem cell use is still speculative, but it is understandable that

some patients who can afford to do so may wish to avail themselves of commercial services offered. However if this is done, it needs to be undertaken safely and will be dependent on the resources of the hospital in which the birth takes place.

• Each NHS trust or hospital providing intra-partum care needs to develop its own policy on how to respond to prenatal requests for cord blood storage through commercial providers, including full economic cost recovery. Because some patients may incur financial obligations by registering with commercial providers before telling their doctors, we advise that this policy should be made available to prospective patients at an early stage. Written advice setting out the hospital’s policy should be made available to all patients when they book for maternity services.

• The RCOG offers the following specific recommendations to NHS trusts who do decide to

support cord blood collection:

− There should be no alteration in ‘usual management’ of the third stage.

− To maximise safety for the mother and infant, collection should be made from the ex utero separated placenta.

− Collection should be by a trained third party (that is, not by the attending obstetrician or midwife) using methods and facilities appropriate to meet the European Tissues and Cells Directive.

− The service should not be made available in cases where the attending clinician believes it to be contraindicated: this will be likely to include all premature births and cases where there appear to the attendants to be specific contraindications, such as nuchal cord or maternal haemorrhage.

Box 6 The Royal College of Midwives (RCM)

The RCM supports the collection of umbilical cord blood if it is medically indicated and for research purposes only. The RCM does not support the commercial collection of umbilical cord blood for stem cell harvesting.

The RCM believes that the current research evidence has not demonstrated that there is any value to be gained from the routine harvesting and storage of stem cells on demand, and that further research is needed in this area.

The RCM welcomes new technologies that enhance the quality of maternity care and provide clear benefits for the great majority of women and their babies. Further, the introduction of new practices should not impact adversely on the quality of midwifery care or the immediate care of the mother and newborn.

Whilst the RCM supports women’s informed choices and decisions, it believes that, there is a need for a wider debate in the NHS on the ethical, legal and safety implications of introducing commercial initiatives into practice where there is insufficient evidence to support its benefits. RCM Recommendations state amongst others that:

• All midwives should acquaint themselves with the evidence and issues around stem cell

harvesting so that they can discuss with women as appropriate.

• The routine collection of umbilical cord blood on demand is likely to have adverse impact

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stage. Trusts should therefore consider whether they have the necessary resources to provide support for cord blood collection on demand.

• Directors of Midwifery service should discuss the legal and practice implications of both

assisting and refusing to assist with cord blood collection on demand with Trust management and lawyers.

Maternity services should develop guidelines/policies, which explicitly state that:

• Midwives are not obliged to collect commercial umbilical cord blood samples.

• Midwives will not be held responsible for the quality or quantity of the sample collected or

for delays in transportation or storage if they chose to assist the mother. Such information should be made available to all women and the companies involved.

• Supervisors of midwives should be involved in all discussions and the development of

local guidelines.

Maternity services should develop an information leaflet (in consultation with geneticists, neonatologists and obstetricians) to offer unbiased, evidence-based information on the indications for collecting cord blood.

NHS trusts vary in terms of cord blood collection. Five hospitals collect specifically for the public banks; four for the NHS cord blood bank and one for the Anthony Nolan Trust cord blood bank (Kings Hospital, London). These NHS hospitals were chosen to increase the numbers of non-Caucasoid ethnic cord bloods, as they serve multi-ethnic areas of the country. The NHS cord blood bank and the Anthony Nolan Trust provide trained staff to recruit donors, obtain consent and collect the donations so that the care of mother and baby is not compromised.

All hospital trusts vary in their policies, or appear to lack recognised policies regarding cord blood collection for private banks. However, it seems that the decision to collect remains that of the midwife and staff attending the birth. Organisations that collect cord blood for storage include the public sector, private organisations, and charity. Whenever an organisation is not allowed to collect the cord blood directly, as is the case for private cord blood banks, and where obstetric or midwifery staff are not able to cooperate on collection, the services of a so-called ‘third-party’ may be used. Private hospital trusts are more open to private cord blood collection, and are also more accessible for third parties. New HTA regulation requires anyone who collects cord blood to be trained to do so.

4.2.3

Figures on collection

The UK figures on collection are shown in Figure 2. This data was kindly provided by the organisations listed in the left column. Collection is subdivided in three different steps:

• Admitted to procedure: From 5,800 annual Expressions of Interest at the NHS cord blood bank, 4,359 were admitted to the procedure of cord blood collection • Collected and processed refers to the actual numbers of cord blood collected

before processing. The 2,426 collected samples are 55% of the numbers admitted, indicating that almost half are lost before collection due to external complications in connection with the pregnancy or delivery, or as a result of no suitable collector being present at the birth. Thus, based on 2,826 (including Virgin) public collections a year and the annual UK birth rate, cord blood is collected for 0.13% of all births

• Retained for storage each year. From the collected samples 75% are retained for storage. On the public side Virgin also collects about 400 samples of which around 320 are suitable for storage. Future Health yearly adds 7,500 private samples to its bank, of which 10-25% are from the UK

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Figure 2 Collection of cord blood in the UK

Collection (unrelated) Admitted to procedure Collected and processed Retained for storage and banking/year NHS-CBB (NHSBT) 4,359 (o7/08) 5,800 EoI 2,426 (07/08) 1,792 (07/08) 1,239 (06/07)

Anthony Nolan Trust 20

Virgin Health bank 400/y (07) ~ 320 (07)

Future Health

Technologies 7,000 – 8,000 (04)$

Source: Technopolis Group analysis

EoI = Expression of Interest; $ = not only in UK

4.2.4

Issues regarding collection

• Cord blood collection requires early clamping of the cord, which has been a routine procedure for many years. However, some research suggests that the outcome of umbilical cord clamping at birth is not well understood and may not be beneficial for the baby

• There are only a few NHS hospitals available for altruistic cord blood donation, which limits the opportunity for voluntary donation

• NHS Trusts generally do not have policies on cord blood collection and defer to professionals

• Typically, 40% of admissions for birth in a collecting centre result in a unit suitable for banking. The majority of attempts are lost between the stages of admission and attempted collection. Of the 40% of admissions that result in collection, 75% are successfully retained for banking, suggesting that handling of samples is fairly efficient

• Private companies and third parties have limited access to NHS trusts. It should be noted that obstetricians might have double assignments as consultants, and act according to public or private practice

4.3

Storage/banking

Initially, cord blood was stored using the same processes for storing peripheral blood, however cord blood is fundamentally different from peripheral blood and should be processed and cryo-preserved appropriately. There are a number of steps for processing cord blood, which include; testing the blood, tissue tying (MHC-HLA) and cell counting, and processing by red cell depletion (which leaves the Mono Nucleated Cells (MNO)) or plasma depletion (to reduce the volume).

Cord blood banking requires substantial initial investment to organise processing and cryo-preservation. Despite this, western governments agree that it is important to organise a public cord blood service and to add data to a worldwide registry, as patients often require donors from abroad. In the UK, the NHS Cord Blood Bank is public but covers only a fraction of the necessary tissue types of the UK. The Anthony Nolan Trust has recently started a cord blood bank, which also provides publicly available units.

4.3.1

NHS-CBB (NHSBT)

At NHS-CBB (see Box 7) cord blood is collected, stored and issued for three different purposes:

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• In Oxford, cord blood is collected for research and units are issued for this purpose within England. In 2007 and 2008, 479 frozen units were made available, however most researchers prefer fresh samples. From 2004-2008 there were 1,468 fresh units collected and issued

• Directed cord blood donations are collected for at risk families who are UK citizens in Oxford, Bristol, Birmingham, Leeds and Sheffield. These samples are designated to treat siblings with an inherited anaemia, metabolic disorder, immunodeficiency, or malignancy. Since 1995, a total of 412 collections have taken place (till May 2008), and two-thirds of which were intended for inherited non-malignant diseases

• After 10 years of directed collections 24 samples have been issued, and the majority (> 80%) have been issued for the treatment of an inherited disease. Related cord blood collection has been extremely efficient; 97% of samples were successfully collected and 88% of the samples met the usual criteria for cell count and volume. However it is policy in the case of directed donation, not to reject units based on these criteria. It is recommended that fully matched designated related units are used for transplantation

• Unrelated Cord Blood Bank Altruistic Collections are collected at Watford, Barnet, Luton & Dunstable and Northwick Park. The samples are stored at Edgware and are available for issue both nationally and internationally. Unrelated altruistic collection commenced in 1996, with the aim to bank 20,000 unrelated donations by 2013. Today (April 2008), 11,270 units are banked, and the number of units is increasing at rates that are somewhat higher than in the early days. The NHSBT public cord blood bank has the second highest percentage of rare tissue types, with 41% of units derived from ethnic minority donors

Box 7 National Health Service Blood and Transplant (NHSBT) Tissue Services The NHS cord blood bank (NHS-CBB) was set up in 1996 to collect, process, store and supply cord blood. The NHS-CBB is public, it is part of the NHSBT and it is free to donate cord blood. By donating cord blood after the birth of a baby, parents are making a voluntary donation that could help any patient who is in need of an unrelated cord blood transplant, in the UK or elsewhere in the world. As NHSBT also provide 2.5 million blood and tissue components each year, the organisation is in a unique position to provide the infrastructure for the NHS-CBB to collect, test, store and issue cord blood in order to provide the opportunity of stem cell transplantation for patients for whom no compatible stem cell donors are available via the registries.

The NHS-CBB provides diagnostic laboratory activities, as well as quality management systems and expertise to ensure good management and practice. Furthermore, NHS-CCB provides medical and scientific expertise, IT systems, the ability to search and provide expert advice on the most suitable HLA match for patients and peer reviewed transplant outcome follow-up data from patients transplanted with NHS-CBB units. The NHS cord blood bank process and test the donations and enter them on international registries, as well as performing final checks and testing prior to issue. The bank is accredited by the European organisation FACT/NETCORD, the Human Tissue Authority and the Medicines and Healthcare Products Regulatory Agency (MHRA) for these activities.

At NHS-CBB 70-80% of collected units are suitable for banking and the average volume is around 70-80 ml (range: 30-300ml). Samples may not be suitable for banking due to (in decreasing order); low volume, low nucleated cell count, refusals, medical exclusions, language exclusions, and processing errors. The average volume and average number of total nucleated cells is slightly higher in people of Caucasoid origin than in Asian or black people.

Cord blood stem cell transplantations serve the treatment of different diseases, and for each type of transplantation a minimum total nuclear cell count is recommended; for malignant disorders 3 x 107 cells/kg are needed, for non-malignant disorders 5 x 107

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cells/kg, and for double transplants 1.5 x 107 cells/kg. The distribution of cell count

reveals that about 50% of all stored samples contain between 50 and 100 x 107 cells

(indicating that a child of no more than 17 kg can be treated with such a unit), around 30% between 100 and 160 x 107 cells, and less than 20% more than 160 x 107 cells.

Hence, about 7,800 samples comply with the TNC recommendations and are suitable for all kinds of treatment. From the issuing overview, it is clear that higher cell count units are more suitable for the matched patients, than the lower count units.

4.3.2

Anthony Nolan trust

The Anthony Nolan Trust (ANT) (see Box 8) is a charity organisation involved in recruiting bone marrow donors and keeping a registry. As the number of people coming forward to donate for the bone marrow registry is declining, this has been a key push factor for the ANT to set up a cord blood bank to accompany their bone marrow registry in December 2007 under a research protocol. They have collected 20 units and are in the process of validating their collecting and processing procedures. The ANT has tissue typing and virology facilities in place for bone marrow donation. A new storage facility in Nottingham will keep the UCB units. Donating to the ANT bank will be free of charge and funded through the ANT. Collection takes place at King’s College Hospital where the ANT pays for an extra midwife who supervises and trains the other midwives. The ANT is hoping to collect 1,500 units a year, approximately a third of the ~5,600 births at King’s College Hospital each year. It is expected that 40% of donations will be fit for transplant and will therefore be included on the register. The remaining units, which are unsuitable for transplants will be donated to research. Future expansion to ten further hospitals is also in the process of negotiation with an aim to increase these figures tenfold. Hospitals are selected for the greatest diversity of ethnicities within the patient population with the aim of gaining a diverse range of units for transplant.

Box 8 The Anthony Nolan Trust (ANT)

The Anthony Nolan Trust (ANT) provides lifesaving donors for patients in need of a bone marrow transplant. A critical factor in the success of a transplant is the accuracy of the match between the patient’s and donor’s cell tissue. Timing is also critical: once a patient has chosen to proceed with a transplant, the donor’s tissue must be available as soon as the conditioning treatment has finished.

The Anthony Nolan Trust connects one person, whose immune system needs a boost – with another person, who is prepared to share a little of theirs. The donor recruitment and management teams organise recruitment clinics, they keep in touch with donors in case they are found to be a match for a patient, they keep records of their tissue-type and they search those records to look for matches.

Since 1974, the Anthony Nolan Trust has helped to give over 5,800 children and adults a new chance of life.

4.3.3

(Public-)private cord blood banks

Private cord blood banks store cord blood samples for autologous use. These samples are usually not tissue typed, and are not part of a registry. The samples stored are also intended for family use, which is not autologous but may be a partial match. Private banks produce forceful advertising, describing the storage of “your own lifesaving” stem cells, and present private collection as a life insurance for a number of serious conditions. They focus more on present use than on future use, which can be misleading, suggesting to the potential client that allogeneic uses of cord blood apply to autologous use. There is currently no standard for marketing messages and the EU regulations do not dictate what can or cannot be said for marketing purposes. Not all private banks are accredited by the Human Tissue Authority and some do not adhere to the regulations (e.g. do not follow appropriate consent procedures and do not

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perform the required blood tests). The lack of standards for cord blood banking in the UK is an issue, which needs to be addressed. The (public-)private organisations described below are fully accredited and would welcome more open deliberations with all stakeholders involved, especially in connection with collection.

4.3.3.1Virgin Health Bank

The Virgin Health Bank (VHB) (see Box 9) receives applications from approximately 400 individuals per year who plan to collect their cord blood, which is ten times less than anticipated when Virgin Health Bank was initiated. From the number of attempts approximately 20% fail each year due to low volume or complications at birth or the midwife refusing to collect the cord blood. They currently store approximately 400 units, 10% of which are for directed donation for families, who due to medical reasons, do not meet the acceptance criteria of the public bank. Around 300-400 units are added to the bank each year, which is expected to increase. No units have been issued for transplant or research. The public-private character of the bank is executed by splitting the samples; 80% of each sample is available for public use, whereas 20% is kept for private use only. Virgin relies on the prospect of advances in research allowing expansion of cells in cord blood, which would be necessary for the cells to be used autologously in due time.

Units collected by the Virgin Health Bank are stored at BioVault in Plymouth. Donations are not treated or enriched before freezing and are stored for 20 years. The average cell dose per sample is TNC 9.28 x 108 cells/ml. The quality storage procedure

follows a standardised method based on the Rubinstein method and all processes have been fully validated. Before freezing samples are tested for: HLA type; infectious disease including HIV and Hepatitis B/C; rhesus factor and blood group factor; rare inherited diseases including Haemophilia, sickle cell anaemia; and all mandatory blood tests.

Box 9 Virgin Health Bank

Virgin offers parents-to-be the opportunity of storing their baby's umbilical cord blood stem cells in a dual private and public stem cell storage bank. As parents’ priority is the health of the family, Virgin acknowledges that it is important to let people know that, in a child's early years; their own stem cells are unlikely to help if they fall ill – they'd need healthy, donated cells – which is why they designed the dual private and public stem cells storage bank in 2006. The chance of a child needing his or her own cord blood for any childhood condition (known as autologous transplantation) is extremely small.

In practice, cell expansion technology is likely to be required to provide a usable number of cells for regenerative medicine regardless of how many are in the original unit collected. The promise of regenerative medicine is not here today, but many expert scientists and doctors believe in its potential.

In 2006 Virgin Health Bank set up the first dual public-private cord blood bank. The dual bank consists of a public bank, which customers donate to, but a part of the sample is stored privately for regenerative medicine purposes.

The Virgin Health Bank works on the premise that the greatest benefit can be derived from access to both allogeneic cord blood from a public pool and access to autologous stem cells for regenerative medicine. The idea is to give parents the “best of both worlds” in the form of access to their child’s privately stored portion and access to a greater public pool. They believe that the uptake for these services will increase in the future.

4.3.3.2Future Health Technologies

Future Health Technologies (see Box 10) has 33 staff to carry out marketing, procurement, processing and storage for cord blood collection and has a full HTA license for these activities. Future Health Technologies has purpose built laboratories and storage facilities in Nottingham. Cord blood units are held under conditions in

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line with the HTA license and according to the EU directives for storage of human tissue. Cord blood units are treated with DMSO before freezing and are stored for up to 20 years. Units are tested for; HLA compatibility; infectious diseases including HIV and Hepatitis B/C; inherited diseases including haemophilia and sickle cell anaemia; Rhesus factor and blood group factor; maternal blood is tested for all mandatory infections. Patient data stored includes; date of birth; nationality; ethnic background; medical and family history, etcetera in line with HTA requirements. Written informed consent is acquired from parents prior to collection. Quality procedures in place consist of following HTA directives.

Over 16,000 samples are currently in storage, sourced from all over Europe, especially Spain, Italy and Greece, as well as the Middle East. No samples have been used for treatment to date. However, four samples are currently in the process of release.

Box 10 Future Health Technologies

Future Health Technologies offer non-invasive cord blood collection and processing, and was the first HTA licensed and MHRA accredited private cord blood stem cell bank in the UK. Future Health processes stem cells according to the strictest UK guidelines and has successfully stored thousands of samples since 2003. The company are anticipating an increase in their activities in the future due to parent demand.

Future Health performs blood counts on all cord blood samples on arrival. The standards set for a useful cord blood sample stipulate that a sample should, as a minimum, have a 250 million total nucleated cell count. If a sample contains less than this, the parents are automatically informed and it is then their decision as to whether they wish the discard of the sample or continue with full storage and pay the associated fee. The widely varying levels of stem cells likely to be present in collected samples is a key reason why they store 100 per cent of each successful sample to maximise the cells available for future use.

Future Health has created two different payment plan options. The plans include the stem cell collection kit, cord blood processing and storage. A client can choose to pay for service yearly or choose a 20-year block to begin.

4.3.4

Figures on banking

The UK figures on storage as described above are depicted in Figure 3. These data were kindly provided by the organisations listed in the left column. 0.019% of the total population have their cord blood stored in a public cord blood bank.

Figure 3 Banking of cord blood

Storage Total number of samples stored

NHS-CBB (NHSBT) 11,270 Altruistic donations since 1996

412 Related donations since 1995 (high risk families) 479 Research (frozen), 07/08

ANT 20

Virgin Health Bank 400 (not for research), 10% related donation Future Health Technologies > 16,000

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4.3.5

Issues on banking

• NHS-CBB has 11,270 samples in storage of which approximately 7,800 have a total nucleated cell count (TNC) suitable for all types of transplantation

• The total number of directed cord blood samples in public storage is small in comparison with both unrelated public banking and autologous private banking • The size of private cord blood banks exceeds the size of public banks

• The aim of the NHS-CBB is to accumulate a sufficient number of units such that all combinations of HLA type are represented. The figure NHS-CBB aim for in order to achieve this is 20,000 units. At the current rate of collection this is expected to take another five or six years

• The figure of 20,000 to achieve a fully representative bank is not used by all public banks. The ANT presented alternative calculations at the Department of Health workshop on cord blood collection, 28th May 2008, as follows. In the UK, 30% of

patients requiring a haematological transplant do not find a donor from the UK or international registries for a 5/6 HLA match. To provide 80% of patients with a 5/6 match it would imply for the UK that 44,472 samples were to be stored, which in turn would require 111,180 collections (given the attrition rate of 60%). With the current yearly rate of accumulation of samples into public storage, it will take another 18 years to reach 44,472 (15 years if Virgin increases the annual number stored from 1,800 to 2,200)

• The above figures show that there would still be a requirement international collaboration of registries to maximise the potential of finding a match for the remaining 20% of patients

4.4

Use

This sub-section discusses the clinical use of cord blood stem cells for haematological disorders, as well as for other clinical use and research into future uses of cord blood.

4.4.1

Clinical haematological use

The initial use of umbilical cord blood stem cells in transplantation was as a replacement for stem cells from bone marrow donation. To date the major clinical indication of cord blood has been for haematological malignancy in children. It is estimated that unrelated cord blood transplants worldwide now account for over 20% of all stem cell transplants. The main limitation to the use of cord blood transplants has been that the yield of cells in a single cord blood is generally too small to use for adult bone marrow transplant, since for a bone marrow replacement a large cell dose is required. However, it is getting increasingly common to use a double or even triple cord transplant for adult bone marrow transplantation. Cord blood units from more than one donor are used, in order to increase the number of cells transplanted, however only the cells from one of the donations will be engrafted. This form of transplantation allows, to some extent, HLA-mismatches with no adverse reactions. Since 2005, more cord blood transplants have been done in adults than in children. Data from Eurocord (see Box 11) and a meta-analysis study show that the long-term survival rate after cord blood transplantation in both children and adults is now comparable to bone marrow transplantation from other graft sources. Moreover, patients transplanted with one- and two-allele mismatched cord blood samples demonstrate transplant-related mortality (TRM) and leukaemia free outcomes that are comparable to fully matched unrelated bone marrow donors. This is an important result that can make stem cell transplantation available to those groups currently underrepresented by the large bone marrow donor registries. Successful cord blood transplantation depends on the quality of the collected cord blood. Volume and cell count are important parameters but also the freezing and storage procedures affect the quality, which is why NETCORD (see Box 12) have developed joint standards for cord blood banking, including standard operating procedures and quality control

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guidelines. Although this has not been verified, there are some concerns that the quality of samples stored before 2006 cannot be guaranteed.

Box 11 Eurocord

The European Group for Blood and Marrow Transplantation (EBMT), an international scientific organisation on haematopoietic stem cell transplants operates a cord blood registry, Eurocord. Eurocord was set up by Professor Eliane Gluckman and is financed by the European Union. Eurocord works in collaboration with NETCORD cord blood banks and EBMT centres. It collects and validates clinical data of patients transplanted with NETCORD cord blood units or patients receiving cord blood units in EBMT centres. During the period from 1988 to 2000, 4,343 cord blood transplants, in adults and children, have been reported to the Eurocord registry from 43 European and non-European countries. The Eurocord database increases each year with approximately 100 cases reported.

Box 12 NETCORD/FACT

The NETCORD Foundation was established in 1988 with the aim of promoting the use of umbilical cord blood for allogeneic stem cell transplantation. It is a non-profit organisation to promote high quality banks and has issued statues and guidelines to promote further research on the collection, processing and preservation of cord blood. NETCORD has established quality standards, in collaboration with the Foundation for the Accreditation of Cellular Therapy (FACT). There are 16 banks registered with NETCORD from 12 countries, this includes the UK NHS cord blood bank. In order to facilitate searches by transplant centres for cord blood units NETCORD has established an on-line search programme, the Virtual Office.

Allogeneic and autologous stem cell transplants are distinctly different procedures, with different clinical indications and different outcomes. Autologous stem cell transplants are used in cases where the underlying disease process does not involve the patient’s bone marrow, in particular as consolidation treatment for some childhood (neuroblastoma) and adult solid tumours (Wilms’s tumour), for salvage treatment of relapsed lymphomas, and for treatment of progressive multiple myeloma. Autologous transplants have a limited role in the treatment of diseases involving the bone marrow itself, which is illustrated by the fact that of the 3,372 umbilical cord transplants that have been performed worldwide in 43 countries (source Eurocord), 2,965 were for unrelated donor transplants, 359 for related and only three were autologous. In 15 years one autologous cord blood transplantation for acute lymphocytic leukaemia has been carried out. Currently, only for acquired aplastic anaemia, has autologous cord blood treatment an unequivocal benefit. Thus, autologous banking of cord blood as biological insurance for haematological disorders is not clinically justified today.

4.4.2

Organisation of use

The organisation of use is depicted in Figure 4.

A Transplant Centre or Consultant Haematologist will always instigate the search for a donor. The service is for patients who require a stem cell transplant and do

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