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The Future of Unrelated Donor Stem Cell Transplantation in the UK
Part 2
Annexes
A Report from the UK Stem Cell Strategic Forum
July 2010
www.nhsbt.nhs.uk
Table of Contents
Abbreviations...................................................................................................................... 6
Glossary............................................................................................................................... 7
Annex 1................................................................................................................................ 8
The Healthcare Benefits of Unrelated Donor Haemopoietic Stem Cell Transplantation in the UK..... 8
Summary................................................................................................................................................ 8
Stem Cells from Adult Donors and Cord Blood....................................................................................... 8
Indications for Unrelated Donor HSCT..................................................................................................... 9
The Growth in Unrelated Donor HSCT in the UK..................................................................................... 9
Patient Outcomes Following Unrelated Donor HSCT............................................................................. 10
The Role of Cord Blood HSCT in Children and Adults............................................................................ 11
Annex 2.............................................................................................................................. 13
The Provision of Stem Cells for Transplantation in the UK.................................................................. 13
Summary.............................................................................................................................................. 13
The Supply of Stem Cells for Transplantation in the UK......................................................................... 13
The Growing Importance of Cord Blood............................................................................................... 14
Annex 3.............................................................................................................................. 17
Meeting the Demand for Stem Cells in the UK..................................................................................... 17
Summary.............................................................................................................................................. 17
Health Related Risks Associated with Stem Cell Donation...................................................................... 17
Inequalities in the Provision of Stem Cells for HSCT............................................................................... 17
Donor Search to Transplant Time.......................................................................................................... 19
Estimating the Unmet Need for Unrelated Stem Cells in the UK............................................................ 19
Likely Changes in Clinical Practice......................................................................................................... 21
Requirement for Donor Stem Cells Following an Irradiation Incident..................................................... 22
Annex 4.............................................................................................................................. 23
Increasing the Availability of Adult Donor Haemopoietic Stem Cells for Transplantation................ 23
Summary.............................................................................................................................................. 23
The Effect of Registry Size on Identifying Matched Donors.................................................................... 23
Increased Resolution of HLA Typing; Creation of a Fit Panel................................................................... 24
Advanced Matching Algorithms............................................................................................................ 24
Importation versus Domestic Supply of Donor Stem Cells...................................................................... 24
Annex 5.............................................................................................................................. 26
Increasing the Availability of Cord Blood Units for Transplantation................................................... 26
Summary.............................................................................................................................................. 26
Optimising the Cord Blood Inventory for the UK................................................................................... 26
A Report from the UK Stem Cell Strategic Forum July 2010
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Annex 6.............................................................................................................................. 28
Supply Chain Options for Improving the Availability of Donor Stem Cells in the UK....................... 28
The Supply of Unrelated Adult Stem Cells............................................................................................. 28
The Role of UK Registries...................................................................................................................... 29
The Performance of UK Registries......................................................................................................... 30
Opportunities to Improve the Supply of Stem Cells from UK Donors..................................................... 30
The Supply of Cord Blood Donations for Transplantation....................................................................... 32
Increasing the Utilisation of Cord Blood Banked in the UK.................................................................... 34
Increasing the Genetic Diversity of Banked Cord Blood Units; Managing the Expectations of Those
Wanting to Donate............................................................................................................................... 35
Annex 7.............................................................................................................................. 36
Financial Appraisal of Options to Reconfigure the Supply Chains...................................................... 36
Methodology........................................................................................................................................ 36
The Current Cost of Providing Unrelated Adult Stem Cells to UK Patients.............................................. 36
The Current Cost of Providing Cord Blood to UK Patients...................................................................... 38
Supply Chain Options........................................................................................................................... 40
The Cost of Adult Stem Cell Provision................................................................................................... 41
The Cost of Cord Blood Provision.......................................................................................................... 43
Annex 8.............................................................................................................................. 46
Health Economic Analysis....................................................................................................................... 46
Summary.............................................................................................................................................. 46
QALY Life Gains following Unrelated Stem Cell Transplantation............................................................. 46
The Cost of Stem Cell Transplantation.................................................................................................. 48
The Current Cost of Providing Stem Cells for Transplantation................................................................ 48
Cost-Benefit Analysis – Establishing a Fit Stem Cell Registry Donor Panel............................................... 50
An Expanded UK Cord Blood Inventory................................................................................................. 51
Profile of Expansion.............................................................................................................................. 55
Cost-benefit Analysis – an Expanded Cord Blood Inventory................................................................... 59
Costs and Cost Savings......................................................................................................................... 61
Health Gains......................................................................................................................................... 62
Complete Assumptions......................................................................................................................... 62
Cost per QALY Results.......................................................................................................................... 63
Univariate Sensitivity Analysis................................................................................................................ 64
Monte Carlo Analysis............................................................................................................................ 66
Conclusions.......................................................................................................................................... 67
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Part 2: Annexes
Annex 9.............................................................................................................................. 68
The Commissioning of Unrelated Donor Stem Cell Transplantation in the UK.................................. 68
Summary.............................................................................................................................................. 68
HSCT Performance in the UK: Challenges and Opportunities................................................................. 68
Standardised Contracts......................................................................................................................... 69
Transplant Centre Output..................................................................................................................... 70
Designation of ‘Centres of Excellence’.................................................................................................. 71
Increasing Understanding Among Commissioners................................................................................. 74
Embedding Best Practice in The UK....................................................................................................... 74
Annex 10............................................................................................................................ 76
The Value of Research and Development In Unrelated Donor Stem Cell Transplantation and
Regenerative Medicine............................................................................................................................ 76
Summary.............................................................................................................................................. 76
Unrelated Blood Stem Cell Transplantation............................................................................................ 76
Cord Blood Stem Cells for Discovery Research....................................................................................... 76
Examples of Key Research and Development Opportunities................................................................... 77
Sale of Cord Blood Stem Cells for Academic and Commercial Research................................................. 79
Securing Cord Blood Stem Cell Research and Development.................................................................. 79
Annex 11............................................................................................................................ 80
Performance Managing the Provision of Unrelated Donor Stem Cells for Transplantation.............. 80
Summary.............................................................................................................................................. 80
Commissioning and Contract Monitoring............................................................................................. 80
Proposed UK Stem Cell Advisory Forum................................................................................................ 80
A UK Stem Cell Registry........................................................................................................................ 82
A UK Cord Blood Inventory................................................................................................................... 83
A UK Database of Patient Outcomes..................................................................................................... 83
Annex 12............................................................................................................................ 84
Stakeholder Consultation....................................................................................................................... 84
Summary.............................................................................................................................................. 84
Recommendations................................................................................................................................ 84
References......................................................................................................................... 91
A Report from the UK Stem Cell Strategic Forum July 2010
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Abbreviations
6
ANT
Anthony Nolan Trust
JACIE
The Joint Accreditation Committee-ISCT
& EBMT
BCSH
British Committee for Standards in
Haematology
MFF
Market-forces factor
BM
Bone marrow
MHRA Medicines and Healthcare products
Regulatory Agency
BMT
Bone marrow transplant
MRC
Medical Research Council
BSBMT
British Society of Blood and Marrow
Transplantation
NCRN
National Cancer Research Network
CB
Cord blood
NHSBT
NHS Blood and Transplant
CTC
Clinical Trials Committee (BSBMT)
NHS-CBB
NHS Cord Blood Bank
CIBMTR
Center for International Blood and
Marrow Transplant Research
NIBTS
Northern Ireland Blood Transfusion
Service
CBT
Cord blood transplant
NMDP
National Marrow Donor Programme
cGMP
Current good manufacturing practice
ONS
Office for National Statistics
CMV
Cytomegalovirus
PBSC
Peripheral blood stem cells
CPA
Clinical Pathology Accreditation
PCT
Primary Care Trust
EBMT
The European Marrow Group for Blood
and Marrow Transplantation
QALY
Quality-adjusted life year
R & D
Research and development
EMDIS
European Marrow Donor Information
System
RIC
Reduced-intensity conditioning
SCG
Specialised commissioning group
SGHD
Scottish Government Health
Department
SCRM
Scottish Centre for Regenerative
Medicine
SNBTS
The Scottish National Blood Transfusion
Service
FACT
Foundation for the Accreditation of
Cellular Therapy
GCSF
Granulocyte colony stimulating factor
GIAS
Graft identification advisory service
GvHD
Graft versus host disease
GVL
Graft versus leukaemia effect
HDI
Human Development Index
TNC
Total nucleated cell count
HLA
Human leukocyte antigen
WBMDR
Welsh Bone Marrow Donor Registry
HRSA
Health Resources and Services
Administration
WMDA
World Marrow Donor Association
ZKRD
HSCT
Haemopoietic stem cell transplantation
German National Bone Marrow Donor
Registry
HTA
Human Tissue Authority
Part 2: Annexes
Glossary
Allogeneic
Transplantation using stem cells from a donor other than the patient
Allomandatory
A patient for whom HSCT using donor stem cells is the only effective therapeutic
option
Apheresis
A process where the blood of a donor or patient is extracted, a particular
constituent filtered out and the remainder returned to the donor or patient’s body
Autologous
Transplantation using the patient’s own stem cells
Antigen
A molecule capable of eliciting an immune response
CD34+ cells
An undifferentiated form of pluripotential haemopoietic stem cells
Cord blood bank
A facility storing processed umbilical cord blood for clinical transplantation. To be
distinguished from ‘stem cell banks’ which may store embryonic stem cell-derived
lines for research purposes.
Engraftment
The process by which transplanted cells regenerate normal blood counts
GvHD
Graft versus host disease - a potentially life-threatening complication where
engrafted donor stem cells mount an immune response against the host
GvL
Graft versus Leukaemia
Haplo-identical
Having the same alleles at a set of closely linked genes on one chromosome
(i.e. a sibling or parental cells)
High resolution typing
Allelic or sequence-based typing that provides additional genetic information on
the donor.
Matching
The degree of parity between the HLA type of a donor and a patient
Intraosseous injection
Injection directly into the bone of the donor
Neutropenia
An abnormally low count of neutrophils, a type of white cell
Stem cell
A cell type found in cord blood, adult blood and bone marrow capable of
repopulating the blood-forming elements of a patient’s bone marrow.
T-cell
A type of white blood cell critical to cell-mediated immunity
Allogeneic
Transplantation using stem cells from a donor other than the patient
A Report from the UK Stem Cell Strategic Forum July 2010
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Annex 1
The Healthcare Benefits of Unrelated Donor Haemopoietic Stem Cell
Transplantation in the UK
Summary
Haemopoietic stem cell transplantation (HSCT) is a life-saving therapy for a range of malignant and non-malignant
diseases. Although HSCT can be performed using autologous stem cells, allogeneic stem cell transplantation is
now established as the most effective treatment strategy in a wide-range of haematological malignancies and
is an increasingly important treatment option in non-malignant bone marrow disorders. Recent advances have
shown that stem cells harvested from a matched unrelated donor or cord blood unit allow the extension of the
curative effect of HSCT to patients who lack a matched sibling donor. The number of UK patients benefiting
from unrelated donor HSCT has grown significantly in recent years, with 749 transplants performed in 2009.
Patient outcomes following HSCT using unrelated donor stem cells are improving, with 1-year survival rates
for transplanted patients at 54% between 2002 and 2006, compared to 42% between 1996 and 2001 and
accumulating data confirms long term survival benefit. HSCT is increasingly an option for older patients and
outcomes now compare favourably with those achieved using sibling donor stem cells. Furthermore, patient
outcomes following cord blood transplantation are now comparable to those achieved with adult stem cells.
Stem Cells from Adult Donors and Cord Blood
Stem cells are characterised by their ability to differentiate into multiple tissue types and cell lineages; they offer
great potential for regenerative medicine. Haemopoietic progenitor cells are multipotent stem cells found in bone
marrow and blood (including cord blood) with the ability to differentiate into red cells, platelets and cells of the
immune system. This ability is exploited in HSCT.
HSCT is either allogeneic or autologous:
• Allogeneic stem cell transplantation is performed with stem cells that are collected from a related or unrelated
donor.
• Autologous stem cell transplantation is performed with stem cells that are collected from the patient before
treatment and are later re-infused
An appropriate human leukocyte antigen (HLA) match is important for all types of HSCT using donor cells.
Individuals inherit pairs of HLA alleles encoding pairs of antigens (e.g. HLA-A, -B, -C, DR, DQ) and a full tissue
match for three antigens pairs is termed a 6/6 match; a full tissue match for five pairs of HLA antigens is termed a
10/10 match. Matching is important: non-matching grafts may be rejected by the immune system of the recipient
and can mount an immune response against the recipient resulting in graft versus host disease (GvHD). The
inheritance pattern of HLA types means that the chance of finding a related fully matched donor is around 30%;
the remaining 70% of patients therefore require an unrelated stem cell donor. Due to the highly polymorphic
(meaning highly variable) nature of HLA, very large numbers of registered donors are required in order for there to
be a reasonable chance of finding a matching unrelated donor.
Stem cells for allogeneic HSCT may be obtained either from bone marrow (BM), peripheral blood (peripheral
blood stem cells or PBSC) or cord blood (CB). The advantages and disadvantages of these sources are described
later in this Annex.
• Umbilical cord blood - donation takes place in hospital maternity departments after birth. There is no
evidence of risk to mother or child providing the collection of cord blood takes place within the normal medical
protocols surrounding birth.
• Bone marrow - collected from the pelvic bones using a needle and syringe. The procedure lasts around half
an hour and is performed under general anaesthetic. The donor is usually recommended to allow a few days
rest to recuperate.
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Part 2: Annexes
• Peripheral blood stem cells - collection is less invasive than for bone marrow. The donor receives four or five
daily injections of GCSF (granulocyte colony stimulating factor) which causes stem cells to move from the bone
marrow to the circulating blood stream. These injections are usually administered in the donor’s home by a visiting
nurse. Collecting the stem cells from peripheral blood is an outpatient procedure. The donor’s blood is removed
and, in a continuous process using an apheresis device, the stem cells are isolated and the remaining blood is
returned to the donor. This process lasts 4 to 5 hours and a second session on the next day may be needed. The
donor may suffer flu-like symptoms as well as minor discomfort during the collection process (OHE 2010).
Umbilical cord blood is rich in haemopoietic stem cells, which are biologically similar to stem cells from adults.
However, stem cells and immune system cells in cord blood are relatively biologically naive and have a greater potential
to proliferate. In addition, cord blood carries a low potential for infectious disease transmission. Cord blood-derived
stem cells have been subject to less genotoxic damage and epigenetic modification than their adult counterparts.
Indications for Unrelated Donor HSCT
HSCT is a rapidly developing field of medicine that saves and extends the lives of hundreds of patients in the
UK every year. Diseases treated by HSCT include haematological malignancies, bone marrow failure syndromes,
metabolic disorders and primary immunodeficiencies. In 2008, the most common indications for allogeneic
HSCT are acute myeloid leukaemia (33.4%), acute lymphoblastic leukaemia (13.4%), myelodysplastic syndrome
(10.6%), non-Hodgkin lymphoma (9.9%) and anaemia (5.7%)(BSBMT, 2009). For the majority of these patients,
alternatives to HSCT using donor cells do not exist; such patients are termed ‘allomandatory’.
Allogeneic transplantation for chronic myeloid leukaemia has declined since 2000 due to the development of
effective non-transplant therapies such as Imatinib (Lee et al, 2010).
The Growth in Unrelated Donor HSCT in the UK
In 2009, 57.6%1 of HSCTs performed in the UK were autologous (BSBMT, 2010), the remainder being allogeneic,
either related or unrelated. Although HLA-matched siblings have historically been the preferred source of donor
stem cells, this remains an option for only 30% of patients; around 70% of patients required stem cells from an
unrelated donor. As a consequence, the use of stem cells from unrelated donors has increased significantly in
recent years (Figure 1). In 2009, 749 unrelated donor HSCT were performed (including 88 using cord blood), up
from 301 transplants in 2001 (BSBMT, 20102). Figure 2 shows that the growth in unrelated donor HSCT in the UK
has reflected global trends. In 1997, according to the WMDA, 3,082 BM donations and just 155 PBSC donations
were issued for transplantation worldwide. By 2009, the number of bone marrow donations had remained stable
(3,445), while the number of PBSC donations had increased to 8,162 (WMDA, 2010). These increases have been
driven by improved transplant protocols (Section 1.4) and facilitated by the expansion of donor registries.
Figure 1 Unrelated donor HSCT in the UK using stem cells from adult donors and cord blood.
700
600
500
400
Transplants
300
200
100
0
2001 2002 2003 2004 2005 2006 2007 2008 2009
(prov.)
Unrelated adult donation Cord Blood
1 Provisional data, including non-1st transplants.
2 BSBMT data for UK HSCT activity in 2009 is provisional at time of writing.
A Report from the UK Stem Cell Strategic Forum July 2010
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Figure 2 Unrelated donor HSCT trends worldwide.
Patient Outcomes Following Unrelated Donor HSCT
Clinical, technological and scientific advances have all contributed to reduced post-transplant morbidity and
mortality following unrelated donor HSCT. Management of cytomegalovirus (CMV) infection has improved and
the incidence of severe graft-versus-host disease (GvHD) has been reduced by strategies such as T-cell depletion of
stem cell donations. The use of reduced-intensity conditioning (RIC) has improved post-transplant morbidity and
resulted in unrelated donor HSCT becoming a viable option for a growing proportion of older patients (Figure 3)
(NMDP, 2010).
Figure 33 The increasing use of unrelated donor HSCT in older patients.
Patient outcomes have also been improved through the increased availability of donor stem cells and a better
understanding of the importance of HLA matching. According to NMDP data, the proportion of well matched
transplants increased from 28% between 1987 and 1998, to 51% between 1999 and 2002 and 65% between
2003 and 2006 (NMDP, 2010). The accuracy of donor HLA typing also improved over that time through the
introduction of improved techniques and quality assessment exercises.
Many factors affect patient outcomes following HSCT including the type and stage of disease, patient age, and
the degree of HLA match between donor and patient. The major causes of post-operative mortality continue
to be relapse, infection, GvHD, and organ toxicity. Nevertheless, through the advances described above, several
different measures of patient outcome have improved consistently over the last 25 years (Karanes et al. 2008;
Lee et al. 2010). Transplant-related mortality has reduced from 46% between 1996 and 1998 to 26% between
2003 and 2006 (NMDP, 2010). Non-relapse mortality rates in the year following unrelated donor HSCT reduced
from 39% of patients in the 1980s to 22% since 2000 (Lee et al. 2010). Finally, one-year survival rates among
3 Adapted with permission from National Marrow Donor Program (NMDP), 2010, Physicians’ Resource Center, www.marrow.org.md
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Part 2: Annexes
transplanted patients increased from 42% of patients between 1996 and 2001 to 54% between 2002 and 2006
(NMDP, 2010). Improvements have been particularly pronounced for certain diseases such as severe aplastic
anaemia, where survival rates doubled between 1987-95 and 2003-06 (Karanes et al. 2008).
The Role of Cord Blood HSCT in Children and Adults
As a result of the developments described above, patient outcomes following HSCT using stem cells from
unrelated donors are now similar to those achieved using stem cells from matched siblings for diseases such as
AML (Appelbaum et al. 2008).
Depending on their source, haemopoietic stem cells have distinct qualities that can affect transplant outcomes.
For example, PBSCs are usually associated with more rapid engraftment, but also a higher incidence of chronic
GvHD than with bone marrow. Cord blood, on the other hand, has a much lower stem cell ‘dose’ than either
source of adult stem cells and is associated with longer periods of post-transplant neutropenia. Unlike adult
donations, cord blood units cannot be sourced repeatedly if there are issues with stem cell engraftment or if the
patient relapses following transplantation.
However, cord blood has several positive characteristics as a source of stem cells. As the T-cells are relatively
immunologically naive, the severity and incidence of GvHD is considerably lower compared to transplantation
using adult PBSC or bone marrow. This allows transplant physicians to use less rigorously matched cord blood
units. An improved understanding of the importance of selecting cord blood units containing a high dose of stem
cells has also helped improve cord blood transplant outcomes. Several techniques are being developed to increase
the rate of engraftment following cord blood transplantation. These include the ex-vivo expansion of stem cells,
the co-infusion of haplo-identical CD34+ cells, intraosseous injection and the combined transplantation of two
cord blood units. Of these, double cord blood transplantation is the most important and is becoming a very
significant therapeutic modality in adult patients. Cord blood also has the advantage of being readily available
and rapidly accessible compared to adult donors (Section 3.2).
Historically, cord blood has been used predominantly for transplantation in children due to concerns that the
low cell ‘dose’ might make it less suitable for patients with a larger body mass. For paediatric patients, cord is
regarded as a readily accessible stem cell source which may achieve less GvHD, improved T-cell reconstitution
(Chiesa et al. In press) and improved graft versus leukaemia (GvL) effect (Eapen et al. 2007; Wagner et al. 2009).
A review of clinical outcomes following CBT in children concluded that, in the absence of a matched sibling,
transplant outcomes for cord blood were comparable and possibly superior to bone marrow, depending on the
circumstances. Though for bone marrow failure, matched bone marrow is still preferable as a source for children
with acute leukaemia cord blood may be equivalent or even superior (Hough et al. 2009). A recent study found
that 5-year leukaemia-free survival for paediatric patients transplanted with 1 or 2 antigen mismatched cord
blood was comparable to using matched bone marrow, while matched cord blood appeared to achieve better
results (Eapen et al. 2007). A meta-analysis of recent outcome studies with unrelated bone marrow transplants
(BMTs) and cord blood transplants (CBTs) concluded that unrelated CBT in children and adults had consistently
equivalent survival outcomes compared with unrelated BMT despite greater donor-recipient HLA disparity with
unrelated CBT (Hwang et al. 2007).
In the adult setting, it has recently become clear that by selecting cord blood units containing high doses of stem
cells and through the use of two units, good outcomes can also be obtained in patients with a higher body mass.
In 2004, two major studies, performed by Eurocord and the Center for International Bone Marrow Transplant
Research (CIBMTR), reported similar outcomes for CBT when compared to unrelated HSCT using BM or PBSC.
These studies concluded that, in the absence of a matched unrelated adult donor, matched or mismatched cord
blood was an acceptable alternative stem cell source (Laughlin et al. 2004; Rocha et al. 2004). Subsequently,
interest in the therapeutic potential of CBT in adults has intensified as a clearer picture of its clinical potential has
developed.
A Report from the UK Stem Cell Strategic Forum July 2010
11
Clinical studies such as those described above have led to a consensus in the UK regarding the use of matched
and mismatched cord blood and adult stem cells for the treatment of different diseases (Shaw et al. 2009). This
algorithm, reproduced at Table 1, is based on the premise that cord blood should be treated as an acceptable
source of stem cells for patients lacking a suitably matched adult donor and that such transplants should be
regarded as a ‘clinical option’, rather than a ‘developmental intervention’.
Table 1 UK Consensus Algorithm for the Selection of Donor Stem Cells
Choice
Family Donor
Unrelated Adult
Donor
Unrelated Cord
Blood
Malignant disease:
paediatrics
1st
Matched family donor
Matched cord (sibling)
2nd
10/10
9/10
6/6
5/6 ( >3 x 107TNC/kg
3rd
8/10
5/6 ( <3 x 107TNC/kg)
4/6
Malignant disease:
adults
1st
Matched family donor
Matched cord (sibling)
2nd
10/10
9/10
3rd
8/10
6/6
5/6 ( >3 x 107TNC/kg
5/6 ( <3 x 107TNC/kg)
4/6
4th
Immunodeficiency
/
Metabolic diseases
1st
Matched family donor
Matched cord (sibling)
2nd
10/10
6/6
3rd
9/10
5/6 ( >3 x 107TNC/kg
5/6 ( <3 x 107TNC/kg)
4/6
4th
Marrow failure
1st
Matched family donor
Matched cord (sibling)
2nd
10/10
3rd
9/10
4th
Reproduced from Shaw et al. (2009).
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Part 2: Annexes
6/6
5/6 ( >3 x 107TNC/kg
5/6 ( <3 x 107TNC/kg
4/6
Annex 2
The Provision of Stem Cells for Transplantation in the UK
Summary
The UK’s three stem cell donor registries now have a combined panel of more than 770,000 adult donors,
compared to around 575,000 in 1997. Of these, the largest is the Anthony Nolan Trust (ANT) with around
405,000 donors, followed by the British Bone Marrow Registry (BBMR) with 310,000 donors and the Welsh Bone
Marrow Registry (WBMDR) with 60,000 donors. This reflects international trends, with 16.4 million donors now
listed at 76 registries worldwide. Cord blood banks have also grown considerably in the last decade: the NHS
Cord Blood Bank (NHS-CBB) now has over 15,500 cord blood donations stored (and 12,435 available for search),
though only around 8,500 of these fall within the revised cell count threshold4. Globally there are 537,000 cord
blood units available for transplant, compared to 44,000 in 1999.
These increases have been accompanied by a substantial shift in stem cell sourcing patterns. A decade ago, bone
marrow provided the majority of stem cells for unrelated donor HSCT in the UK; PBSC donations now account
for 85% of the UK’s adult stem cell use. However, despite slow uptake by the UK transplant community and
uncertainty surrounding its application, cord blood has developed into an important source of stem cells. Its
use has now extended to adult patients with growing success. Current trends suggest that it is likely to become
increasingly important in the future.
The Supply of Stem Cells for Transplantation in the UK
Registries of Adult Donor Volunteers
Patients lacking a suitably matched family member require a matched unrelated donor. The likelihood of identifying
a suitable donor is largely determined by the HLA type of the patient and the size and diversity of adult registries
and cord blood banks. The significant expansion of donor registries and cord blood inventories in the UK and
internationally has therefore been critical in facilitating the steady rise in the number of unrelated donor transplants.
The ANT was the first UK donor registry to be established in 1974 and now lists 404,888 stem cell donors. The
BBMR lists 309,258 donors and the WBMDR lists 59,696 donors (WMDA, 2010).
This growth reflects global trends: there are now 76 international registries with a total of 16.4 million available
donors. Increasingly stem cells are provided across national boundaries (Figure 4). Despite its increasing domestic
capacity, in 2009 the UK provided 305 (43%) of BM and PBSC donations nationally while 400 (57%) donations
were imported. The majority of these were sourced from the German National Bone Marrow Donor Registry
(ZKRD) in Germany and the National Marrow Donor Program (NMDP) in the United States (WMDA, 2010).
Figure 4 Worldwide trends in the national and international provision of stem cell donations for HSCT
4 The total nucleated cell (TNC) count of a cord blood unit is an important determinant of its clinical value (Annex 1). In May 2010 NHSBT raised the minimum
threshold for storage from 4 x 108 TNC to 12 x 108 TNC for Caucasian donors and 9 x 108 TNC for ethnic minority donors.
A Report from the UK Stem Cell Strategic Forum July 2010
13
Cord Blood Banks
More recently, cord blood banks have been established in the UK and abroad and are now expanding rapidly.
The NHS-CBB was the second CBB to be established worldwide. It has the UK’s largest cord inventory with
over 15,500 cord blood units banked and 12,675 units listed on the BBMR. It is the only facility in the UK to
have issued cord blood units for a domestic transplant and has currently provided over 310 cord blood units for
transplantation.
Internationally, cord blood banks worldwide now have a combined inventory of over 537,000 cord units. This
compares to only 44,000 units in 1999. The UK’s cord blood resources are still developing and, in common with
other countries, it remains reliant on international cord banks, particularly those in the United States. In 2009, 16
(15%) of cord blood units were provided nationally, and 91 (85%) of units were sourced from abroad.
The Growing Importance of Cord Blood
Two trends can be identified over the last ten years, both globally and in the UK. The first is the diminishing use of
bone marrow in favour of PBSC (considered above, Figure 2); the second is the increasing use of cord blood over
adult stem cells. Until recently, cord blood made a relatively marginal contribution to HSCT in the UK, especially
when compared to other countries such as Spain, France and the USA. This was in part due to the successes
being achieved by UK transplant physicians using alternate strategies such as T-cell depletion and haploidentical
transplantation when no matched sibling or unrelated donor was available (Technopolis, 2009). The UK use of
cord blood is compared with other Countries in Figures 5 and 6 (WMDA, 2009).
Figure 5 Types of stem cell donation transplanted by country
Figure 6 The use of cord blood in unrelated HSCT
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Part 2: Annexes
The use of cord blood in the UK is now increasing; in 2009, of the 812 stem cell donations supplied for
transplantation, 104 (13%) were bone marrow, 601 (74%) were PBSC and 107 (13%) were cord blood units. This
reflects the increasing use of cord blood for unrelated donor HSCT in the UK (Figure 7).
Figure 7 The increased use of cord blood in the UK for unrelated donor HSCT
The recent increase in the use of cord blood in the UK is forecast to continue in light of the developing body
of evidence regarding post-transplant outcomes in children and adults and a developing national consensus on
its use for a range of diseases. Cord blood transplantation now accounts for around 30% of unrelated donor
HSCT for patients under the age of 16). With the development of double cord blood transplants, it is increasingly
utilised in adults too. Since 2008, adult transplants using cord blood have exceeded the total number of paediatric
cord blood transplants (Figure 8) as the number of unrelated donor HSCT performed in adults is much higher
(NMDP, 2010).
Figure 8 The growing proportion of cord blood transplants on adult patients, 2000-09
A recent review of the UK’s cord blood services, commissioned by the Department of Health, highlighted
the absence of a national policy on cord blood and recommended that a framework should be developed in
conjunction with a high-level advisory committee (Technopolis, 2009). The report notes that although the use
of cord blood in the UK was growing, current usage is lower than countries such as Spain (Figure 9), where the
investment in cord blood banking has been much greater: while its registry has only 80,314 registered adult
donors, its cord bank has 41,771 available cord units (WMDA, 2010).
A Report from the UK Stem Cell Strategic Forum July 2010
15
In summary, cord blood is likely to become an increasingly significant source of unrelated donor stem cells in the
coming decade. Great Ormond Street Hospital, the largest paediatric stem cell transplant centre in the UK has,
in the last few years, shifted its stem cell use towards cord blood which is now used in more than 50% of the
transplants it performs (Figure 9). This trend is likely to be followed by other paediatric centres. A similar pattern
of significantly increased cord blood transplant activity is predicted in the adult population.
Figure 9 The increasing use of cord blood for transplantation at Great Ormond Street Hospital, 2007-2010
40
35
30
25
Transplants 20
15
10
5
0
2007
16
Part 2: Annexes
2008
2009
2010
Adult donations
Cord blood
Annex 3
Meeting the Demand for Stem Cells in the UK
Summary
HSCT is a life-saving therapy. The majority of patients referred for transplant have no acceptable alternative
cure. Despite the millions of registered volunteers available globally, many patients fail to locate a suitable donor,
particularly among ethnic minorities. This is because the HLA haplotypes found in ethnic minority individuals are
poorly represented in donor registries. While around 90% of Caucasians may typically find a match, for ethnic
minorities the matching rates may be as low as 10%. Furthermore, many patients who are successful in locating
a donor fail to be transplanted due to death or deterioration. For them, an important contributing factor is the
several months it may take to confirm the availability and suitability of a stem cell donor and to arrange for stem
cell collection. For these patients, the ready availability of a matched cord blood unit may be life-saving. Overall,
current levels of unmet need are estimated to be approximately 440 patients in the UK annually. However, an
adequately sized cord blood bank would provide 370 of these patients each year with rapid access to suitable stem
cells for transplantation. This would cure around 200 patients in the UK each year of an otherwise fatal illness.
Health Related Risks Associated with Stem Cell Donation
In the overwhelming majority of cases, obtaining stem cells from bone marrow and peripheral blood does not
impose long term adverse consequences on the donor. Instances of sepsis, pelvis fractures and splenic rupture
have occurred, but only very infrequently (Pamphilon et al. 2009). Nor is there any evidence to support earlier
concerns that the use of G-CSF might be associated with the development of myeloid malignancy in healthy
allogeneic donors (Pamphilon et al. 2008). However, transient symptoms are common: recent follow up surveys by
the NMDP found that 70% of donors experienced headache, myalgia and fatigue and 80% suffered bone pain.
In addition, around 0.6% experienced unexpected toxicities, though they all recovered (Pulsipher et al. 2009).
Fatalities and life-threatening incidents are rare, but have been reported: a recent review of 51,024 allogeneic
transplants performed between 1993 and 2005, primarily in Europe, reported five donor deaths and 37 severe
adverse events, including subarachnoid haemorrhage (Halter et al. 2009).
Though the long term risks of adult donation are minimal, cord blood poses no risk to the mother if collected
without modification at the third stage of labour, in accordance with standard UK birthing protocols. Collection
as performed by the NHS-CBB does not interfere with the management of the birth and only occurs after the
baby is born. For the baby, the advantages of delayed cord clamping are improved iron stores and a lower risk of
an intraventricular haemorrhage, though there is a raised probability of jaundice requiring phototherapy (Downey
and Bewley, 2009).
Inequalities in the Provision of Stem Cells for HSCT
Unrelated donor HSCT is a life-saving therapy, referred to as ‘allomandatory’ for the patients for whom it is
the only treatment with a reasonable chance of cure. Even with the expansion of international registries, many
patients in need of unrelated donor HSCT fail to receive a transplant. Of the 151,000 patients qualifying for
an unrelated donor transplant between 2000 and 2006, only 64,720 actually received one (Van Rood and
Oudshoorn, 2008).
Patients from ethnic minorities are particularly disadvantaged. This is because HLA types are related to ethnicity
and ethnic minority donors are underrepresented on registries. Of the donors registered on the BBMR, only
5.1% of donors are non-Caucasian (including 1.7% Asian, 1.2% Black, 1.2% mixed race and 0.3% Oriental). To
remedy this, targeted recruitment drives by major registries have had some success. A review of the ANT registry
in 2005 showed its composition to be more closely aligned with that of the UK population (4.3% Asian, 3.7%
Black, 0.4% Oriental).
A Report from the UK Stem Cell Strategic Forum July 2010
17
This impacts substantially on the prospects of ethnic minorities successfully locating a match. BBMR data on
matching rates suggests that Caucasian patients are more than twice as likely (88%) to locate a suitably matched
donor than mixed race patients (40.7%)(BBMR, 2004/5), as illustrated in Figure 10. Similarly, Shaw et al, (2009)
report that while up to 30% of Caucasian patients in the UK may be unable to find a 9/10 or 10/10 volunteer
adult donor match, for ethnic minority patients this figure is as high as 70% (Shaw et al, 2009). This is mirrored in
other major international registries, such as the NMDP, where the identification of a 7/8 or 8/8 matched unrelated
donor occurs for more than 90% of US patients of European Caucasian ancestry, more than 70% for those of
Asian or Hispanic ancestry, and more than 60% for those of African ancestry (B. Shaw, personal communication,
cited in OHE, 2010). A recent survey of 398 searches in the United States found that 89% of Caucasians, 77% of
Hispanics but only 52% of African Americans were able to find a 7/8 or 8/8 matched (OHE, 2010). Consequently,
it cannot be assumed that Black and minority ethnic patients unable to locate a donor with a UK registry will be
able to identify a suitable match in an international registry.
Figure 10 Patient matching rates by ethnicity (2004/5)
The challenge of identifying matched adult donors for Black and ethnic minority patients is further increased by
other factors, including:
• The greater HLA heterogeneity among certain ethnic groups – different ethnic groups have differing levels
of HLA heterogeneity. The probability that two randomly selected African-Americans will have an HLA match is
about a tenth of the equivalent probability of a match between two Caucasians (Bergstrom et al. 2009).
• A smaller donor pool – as ethnic minorities have a smaller population base, even with comparative levels of
representation to Caucasians, ethnic minority patients will have a smaller selection of potential matches.
The banking of umbilical cord blood offers an opportunity to reduce this inequality. It is difficult to increase the
representation of specific ethnic minorities on a volunteer donor panel, but considerably more practicable to
focus collection of cord blood at hospital maternity units that serve populations with relatively high levels of
ethnic diversity. Through targeted collection in this way, currently underrepresented HLA types can be made much
more available. This would benefit not only ethnic minorities in the UK but also the same ethnic groups in other
countries around the world. The NHS-CBB currently has 39.5% ethnic minority representation among its stored
units (BBMR, 2010). This is similar to the NMDP in the United States: 44% of its listed cord units are sourced from
ethnic minority donors (NMDP, 2010).
An additional advantage is that, due to its tolerance of higher levels of HLA mismatch between patient and donor,
cord blood can be used with greater flexibility for transplantation on patients with rare haplotypes who lack a
similarly matched donor.
18
Part 2: Annexes
Donor Search to Transplant Time
The progression of a patient’s disease prior to HSCT is an important contributing cause of treatment failure and
death. A study of 3857 transplants between 1988 and 2003 found that, compared to patients transplanted at an
early stage of their disease, the mortality risk for intermediate-stage patients was 38% higher. For advanced-stage
patients, the risk was roughly double (Lee et al. 2007).
The duration of a patient’s waiting period frequently determines whether he or she is able to receive HSCT.
Currently, search-to-transplant time using adult donor stem cells takes a median of four months (Kernan et al.
1993; Barker et al. 2002) and during this period patients may relapse or die (Davies et al. 1996; Dini et al. 2003).
A survey of outcomes at King’s College Hospital during 2005 found that, while 28% of patients failed to locate
a donor, an additional 33% who successfully found a suitable donor were unable to undergo the procedure as a
result of deterioration during the donor search. Overall, only 38% of allomandatory patients in the sample study
were actually transplanted (Querol et al. 2009a).
The problem of extended waiting periods applies particularly to adult donations. Cord blood units, unlike adult
volunteers, are stored in situ and therefore readily accessible for confirmatory testing and shipping when a
transplant centre makes a request. A survey of referrals reported a median of only 13.5 (range, 2-387) days to
search and choose a cord blood unit for transplantation, compared to 49 (range, 32 to 293) days to obtain a
suitable unrelated adult donor (Figure 11) (Barker, 2002). This translates into shorter search-to-transplant times for
cord blood HSCT.
Figure 11 Search times for bone marrow donations and cord blood units
BONE
MARROW
CORD
BLOOD
Donor identified
19 days
(1-257)
30 days (10-101)
50 days
(32-293)
13.5 days
(2-387)
Formal search time
Donor available
It is also possible to reduce waiting times and raise the certainty of an appropriate and reliable donor being
identified through the development of a ‘fit’ panel of donors. This is discussed in greater depth in Annex 4.
Through regular contact with registered volunteers, the high resolution typing of preferentially selected donors
and new recruits, and the use of a predictive search algorithm supported by specialist advisory services, searchinitiation-to-transplant times would be reduced by 4 to 6 weeks (D. Marks, personal communication to the
review).
Estimating the Unmet Need for Unrelated Stem Cells in the UK
Unmet need includes the proportion of patients unable to find a match as well as the patients who may currently
locate a suitable donor but who fail to be transplanted due to donor-related issues: donors may be difficult to
trace, prove medically unfit for donation or withdraw their consent. As discussed above, a significant number of
patients die or deteriorate physically while waiting for a transplant.
A Report from the UK Stem Cell Strategic Forum July 2010
19
Failure to Find a Match – Caucasian Patients
During 2009, 661 unrelated adult HSCT were performed in the UK (data from BSBMT, 2010). If it is assumed that
these were all Caucasian patients and if 20% of Caucasian patients are unable to identify a suitable match, then
the unmet demand from Caucasians can be estimated as:
(0.2/0.8) x 661 = 166 patients per annum
The unmet demand from failure to find a match for Caucasian patients is therefore circa 170 patients per annum.
Failure to Find a Match – Ethnic Minority Patients
Ethnic minorities make up 10%5 of the UK population. If it is assumed that 10% of the demand for unrelated
donor stem cells comes from ethnic minorities, then the unmet demand can be estimated as:
(0.10/0.90) x (661/0.8) = 92 patients per annum
The unmet demand from the failure to find a match for Black and ethnic minority patients is therefore circa 90
patients per annum.
Demand Currently met by Cord Blood Donations
During 2009, 88 transplants were carried out using cord blood; of these, 17% went to ethnic minority patients
(Regan et al. 2010). Subtracting these from the above unmet demand estimates yields:
Caucasian unmet demand from failure to find a match = 93 patients per annum
Ethnic minority unmet demand from failure to find a match = 77 patients per annum
Unmet Demand due to Patient Factors
12% to 33% of patients with a matched unrelated adult stem cell donor do not proceed to transplant due to
patient factors such as disease progression and toxicity to additional chemotherapy. It is assumed 50% of these
patients would benefit from a rapid cord blood transplant. So unmet demand for these patients can be estimated
as between:
(0.12/0.88) x 661 x 0.5 = 45.1 patients per annum and (0.33/0.67) x 661 x 0.5 = 163 patients per annum.
Taking the mid-point, the unmet demand from patient factors is around 110 patient per annum.
Further Demand due to Substitution
For unrelated adult donations, optimal patient outcomes are achieved using PBSC or bone marrow matched for
9/10 or 10/10 HLA-A, -B, -C, -DR and -DQ alleles (N. Russell and B. Shaw, personal communication to the review).
For patients unable to locate a 9/10 or 10/10 matched donor or requiring urgent transplantation, a cord blood
unit is an acceptable alternative stem cell source. For a CBT, the current minimum acceptable standard is a
4/6 HLA-A, -B and –DR match (Querol et al. 2009a) and so it provides wider access to patients with rarer HLA
haplotypes. Moreover, for CBT, acceptable matching at HLA-A and HLA-B loci can be achieved at lower resolution
than required for unrelated adult donations.
5 This figure is based on ethnic minority population shares in England and Wales, Northern Ireland and Scotland, weighted by total population. 2008
population data was used, 2007 experimental data was used for England and Wales ethnic minority shares and 2001 data was used for Scotland and
Northern Ireland ethnic minority shares.
20
Part 2: Annexes
It is estimated an additional 70 cord blood transplants could be carried out each year to replace 9/10 HLA
matched adult donor stem cell transplants.
Total Unmet Demand in the UK
From the above, it follows that the unmet need for donor stem cells is circa 170 + 90 + 110 + 70 i.e. 440
patients per annum.
Meeting Unmet Demand via an Increased Inventory of Cord Blood Units
Optimising the cord blood inventory for the UK is discussed below. Querol et al. (2009a) estimated that a UK
inventory of 50,000 cord blood units would be able to meet:
• 85% of the unmet need from Caucasian patients
• 50% of the unmet need from Black and ethnic minority patients
• 90% of the unmet need from patients whose conditions deteriorate while waiting for an adult donor
• 100% of the unmet need from patients who would have received a 9/10 HLA matched bone marrow
donation.
Thus, the extra number of UK patients who would be treated from a UK cord blood inventory of 50,000 units
would be:
Caucasian demand met: 150 patients per annum
Black and ethnic minority demand met: 50 patients per annum
Patient factors: 100 patients per annum
Adult donor stem cell recipients: 70 patients per annum
In total, the extra number of patients treated in the UK from an increased cord blood inventory
would be 370 (out of a potential 440). However, the number of cord blood units issued would be greater than
370, since two thirds of adults will probably receive double cord blood transplants. Assuming that two thirds of
adults receive double cord blood transplants, but all children receive single cord, it is estimated that 1.57 cord
blood donations are used per transplant (D. Marks, personal communication to the Review). This would amount
to 580 cord blood units per annum.
Assuming that around 60% of transplants are successful and that patients who do not receive HSCT have little
or no life expectancy, this means that 200 patients (1000 life years) would be cured of an otherwise fatal disease
annually.6
Likely Changes in Clinical Practice
Changes in practice in the next decade are difficult to predict, but rates of transplantation are likely to increase
as HSCT is increasingly applied to older and infirm patients as ‘salvage’ chemotherapy improves. Increased
rates of transplantation are likely in acute myeloid leukaemia, lymphoma, myelodysplastic syndrome, and acute
lymphoblastic leukaemia: a significant proportion of these patients will be in an unstable remission and require
urgent access to HSCT.
6 Recent studies have shown survival rates of around 50% following cord blood transplantation for ALL (49% 5-year survival, Tomblyn et al. 2009; 50% 3-year
survival, Bachanova et al. 2009) and almost 80% for certain conditions such as Hurler’s syndrome (77% 3-year survival, Boelens et al. 2009). It is anticipated
that outcomes for good risk adults and children will reach 55%-60% during the 4-8 year period of expansion of the cord blood inventory.
A Report from the UK Stem Cell Strategic Forum July 2010
21
Requirement for Donor Stem Cells Following an Irradiation Incident
Stem cells may have value following an irradiation event. Though unlikely, an event which irradiated a significant
number of individuals could affect their haemopoietic, gastrointestinal and neurological systems. Individuals
receiving between 4 and 10 Gy of total body radiation may benefit from stem cell transplantation. However,
in an emergency context, the established network of registries might be impaired. Furthermore, many donors
could be irradiated themselves or unwilling to attend a hospital close to an area affected by radiation. In these
circumstances, a cord blood bank could play a critical role in providing patients with a reliable and readily
accessible source of stem cells7. The Department of Health has identified cord blood as a central component of its
contingency plan. Cryopreserved cord units could be supplied for transplantation within a matter of days. Due to
its capacity to successfully engraft with relatively high levels of HLA mismatch, an adequately sized bank would
provide a 4/6- or 5/6-HLA donor match to as much as 90% of affected individuals.
7 It should be noted that the efficacy of cord blood in this setting has not been tested, and its slow engraftment might not be appropriate for patients with
prolonged neutropenia.
22
Part 2: Annexes
Annex 4
Increasing the Availability of Adult Donor Haemopoietic Stem Cells for
Transplantation
Summary
The UK now has in excess of 770,000 registered adult volunteers, with millions of additional donors available
globally. Increasing the number of donors registered would not significantly increase the chances of UK patients
identifying a matched unrelated adult donor. Greater impact on patient outcomes would be achieved through
measures to decrease the time taken to provide high quality adult donor stem cells. The latter can be achieved
through, the creation of a ‘fit’ panel of available adult donors. This would be achieved by high resolution typing
new recruits and selectively targeting registered donors with a favourable demographic profile as potential
donors. By providing further samples for typing, these donors would also confirm their continued availability
and willingness to donate. Furthermore, registry searches would be enhanced by the use of a predictive search
algorithm that would preferentially list the optimal donor profiles for selection by transplant centres.
The Effect of Registry Size on Identifying Matched Donors
Though adult registries provide a large proportion of patients with a suitably matched donor, it is unlikely that this
proportion can be increased significantly by further increasing the size of adult donor registries. The number of
UK patients currently unable to find a matched unrelated donor is described in Annex 3. Figure 12 shows that as
registries become larger, the gain in improved matching rates with every additional donor becomes increasingly
marginal. By extrapolating from German registry data, increasing a European registry size from 500,000 to
1,000,000 donors raises the proportion of patients finding a matched donor by about 5%. Thereafter, for every
million new donors added, search success rates rise by around 2% (S. Querol, personal communication to the
review). A registry of 10 million donors would require a further 7 million additional donors to increase donor
identification rates by 1% (Hurley et al. 2003).
Registry expansion has substantial associated costs; significant investment is required to both expand and
maintain the donor base against annual donor attrition rates of around 2%. For these reasons, registries focus
effort on increasing the genetic diversity of the panel through targeted recruitment of Black and ethnic minority
donors.
Figure 12 Relationship between matching rate and size for large European donor registers (data provided by C. Muller,
personal communication to the review).
A Report from the UK Stem Cell Strategic Forum July 2010
23
Increased Resolution of HLA Typing; Creation of a Fit Panel
HLA typing can be undertaken to low resolution (sometimes called serological) or high resolution (sometimes
called allelic or sequence-based). High resolution typing provides additional genetic information of the donor, and
matching at this level improves patient outcomes. The majority of HLA information held on registry donors is at
low resolution. As a result, transplant centres require donor registries to arrange for further high resolution typing
of selected donors to confirm suitability for transplant. This step adds delay in the provision of donor stem cells.
As a result, transplant centres increasingly choose to source unrelated adult stem cell donors from registries listing
HLA types at high resolution.
Registered donors may be retrospectively retyped at high resolution. Young, medically fit donors with a confirmed
willingness to donate would be chosen for retrospective typing to create a ‘fit’ panel of reliable donors.
Additionally, donors with a locus ‘missing’ (e.g., HLA-C) or for whom allele level typing will resolve important
ambiguities (e.g. B*44, DR*04 and *07 etc) should be preferentially retyped. Donors with rare HLA haplotypes
would not be retyped, as they are likely to be the only available donor. Once a fit donor has been requested,
transplant centres would have a high level of assurance that the donor will be a suitable match, will not refuse to
donate, and can be provided rapidly. High resolution typing would therefore result in increased utilisation of the
UK’s donor registries, both for domestic use and for export.
Advanced Matching Algorithms
High resolution typing of donors by DNA sequencing is costly and labour intensive. Registries such as the NMDP
and ZKRD have therefore developed computer programmes (HapLogic and OptiMatch) capable of predicting
precise matches. These prognostic matching algorithms use all partial information available on each donor in
combination with high resolution 3-locus-haplotype frequencies of the underlying population to calculate the
probability of a donor to be allele identical for each of the loci HLA-A, -B and -DRB1 as well as all three loci
combined. By using advanced matching algorithms in this way, high resolution typing is used to validate the
predictions rather than to type a high proportion of registry donors. In this way, search to transplant times are
reduced in the most cost effective manner.
Importation versus Domestic Supply of Donor Stem Cells
The UK imports around 50% of its unrelated adult donations and 85% of its cord blood units, primarily from
Germany (the ZKRD registry) and the US (the NMDP registry). Tables 2 and 3 show ANT data on the costs of stem
cells imported from different countries in 2009.
The UK will always rely on international donor registries to satisfy part of its demand, as will other countries.
However, the relative proportion of UK-sourced units could be raised. Increasing the UK’s capacity to meet its
need would have a number of advantages including the potential to reduce search to transplant times.
Table 2 The importation of adult stem cell donations
Rank
1st
2nd
3rd
4th
5th
6th
7th
8th
9th
10th
24
Country
Germany(ZKRD)
US (NMDP)
Australia
France
Canada
Israel
Cyprus
Portugal
Italy
Other
Part 2: Annexes
Number Imported
187 (48%)
131 (34%)
11 (3%)
8
7
7
6
6
5
18
Cost per Donation
£10,500
£17,222
£13,500
£11,273
£16,451
£12,903
£15,000
£11,363
£11,902
Table 3 The importation of cord blood units
Rank
1st
2nd
3rd
4th
5th
Country
US (NMDP)
US (New York)
Barcelona
Dusseldorf
Other
Number Imported
33 (37%)
16 (18%)
14 (16%)
13 (15%)
13
Cost per Donation
Up to £36,000
£23,000
£19,593
£18,286
Crucially, domestically sourced donors and cord blood units reflect the unique genetic diversity of the UK
population in a way that registries in other countries cannot. This is particularly important in light of the growing
mixed race population in the UK. In addition, by achieving stronger control over its own supply, the UK would
strengthen the logistical links between its providers and transplant centres and have greater protection against
disruptions in the global supply chain. In 2010, the closure of international flights in many parts of Northern
Europe highlighted the relative fragility of the global supply chain. Finally, a well developed supply of donor stem
cells would position the UK to fully exploit its position as world leader in cell-based therapies. This is discussed
further at Annex 10.
By reducing importation and increasing the export of adult donor stem cells and cord blood, the UK’s stem cell
services would also become more cost effective. Germany’s donor registry is the exemplar for this business model.
In 2009, the ZKRD exported 70.6% of its PBSC and bone marrow donations and relied on imports for only 16.1%
of its adult stem cell donations. Worldwide, around 60% of adult donations sourced internationally were provided
by the ZKRD during 2008 (WMDA, 2010).
Currency fluctuations and rising tariffs from overseas registries are factors over which the UK has little control.
Domestically sourced adult stem cell donations (£11,950 from the ANT and £12,712 from the BBMR, 2009/10
prices) are not significantly higher than the median international cost (£12,400). For cord blood units, importation
costs are relatively high. The cost of an NHS-CBB cord blood unit (2009/10 price) is £12,712 compared to around
£20,000 for an imported unit; the price for an imported cord blood donation from the US may be as high as
£36,000.
A Report from the UK Stem Cell Strategic Forum July 2010
25
Annex 5
Increasing the Availability of Cord Blood Units for Transplantation
Summary
Developing the UK’s cord blood inventory to an optimal size of 50,000 units would ensure the availability of
donor stem cells for 80% of the UK population. In particular, through targeted collection and by exploiting the
biologic characteristics of cord blood, matching rates for ethnic minority patients would be significantly increased.
To achieve optimal results, the bank should collect at least 30% donations from ethnic minority women. In
addition, as the cell dose of a unit substantially effects its outcome and consequently its likelihood of being
selected by transplant physicians, only units satisfying a minimum cell threshold of 9 x 108 TNC should be banked
to guarantee the clinical effectiveness of the inventory.
Optimising the Cord Blood Inventory for the UK
To achieve maximum patient benefits, a national cord blood inventory must be:
• optimally sized
• genetically diverse
• store units containing a high dose of stem cells.
Inventory Size
Increasing the size of a cord bank will expand the range of rare HLA haplotypes in its inventory, raise the
proportion of successful patient searches and the quality of HLA matches. However, while increased cord bank
size will result in better patient outcomes, the relative value of each added unit diminishes as the inventory
expands. On this basis, balancing service quality with cost effectiveness, a bank of 50,000 units has been
determined as optimal for the UK, with 80% of patients locating at least one 5/6 HLA-matched cord blood
donation (Table 4). A further increase to 100,000 banked cord blood units would increase the chances of locating
a 5/6 match to 86% (Querol et al. 2009b).
Table 4 Donor matching rates, according to panel size and ethnicity (from Querol et al, 2009b)
Match category
Four out of six or better
Five out of six or better
Six out of six
Donor panel size
10,000 donors
50,000 donors
86% to 95%(54)* 96% to 98%(261)
32% to 64% (2)
49% to 80%(9)
3% to 19%(0)
9% to 34%(0)
100, 000 donors
99% to 99·6% (532)
63% to 86%(19)
13% to 41%(0)
*Minimum figure corresponds to the success rate (%) for ethnic minority patients and the
maximum figure corresponds to overall success rate for all patients. Figures in parentheses
represents the median number of potential donors per patient matched in overall population
Ethnic Minority Representation
In the absence of a strategy to preferentially collect cord blood from ethnic minority women, a UK cord blood
bank will contain around 15% of stored units from ethnic minority donors (Querol et al. 2009b). In this scenario,
matching rates of for non-Caucasian patients would be around 36%, compared to 80% for the population as a
whole. With 30% ethnic minority representation, the probability of a match is 52% for ethnic minority patients
and 74% for the population as a whole. A bank with 50% ethnic minority representation would deliver equitable
outcomes (67% and 71%). For an optimally sized bank of 50,000, 30-50% of its inventory should therefore
be sourced from ethnic minorities. This can be achieved by locating collection sites, as is currently the case, in
ethnically diverse communities. Around 40% of the cord units collected by NHS-CBB are provided by donors from
ethnic minorities.
26
Part 2: Annexes
The Dose of Stem Cells in Banked Cord Blood Units
The number of total nucleated cells (TNC) in a donation of cord blood is a useful surrogate measure for its
number of stem cells. A typical cord blood collection contains 8 x 108 TNC, but there is considerable variation
between donations. Cord blood donations containing a high dose of stem cells are associated with faster
post-transplant engraftment and improved patient outcomes (Annex 1). As a consequence, transplant centres
preferentially select cord blood units containing a high dose of stem cells. The median number of cells in
transplanted units is 14.5 x 108 and 18.8 x 108 for paediatric and adult patients respectively (WMDA, 2010).
A cord bank with 50,000 units and a banking threshold of 5 x 108 TNC is likely to provide searching patients with
a 69% chance of locating a median of three 5/6 HLA-matched samples. A similarly sized bank with a 9 x 108
threshold for banking would provide 75% of patients with a median of 6 suitable donations. With a threshold of
12.5 x 108, patients would have an 80% chance of locating a median of 9 viable units. However, it would also lead
to a higher discard rate for collected units. The optimum banking threshold therefore needs to balance the cost of
increasing utilisation of the inventory with the higher rates of ‘discard’. The acceptable minimum has therefore been
put at 9 x 108 TNC (Querol et al. 2009b). Figure 13 summarises the rationale and patient benefits of an optimised
cord blood inventory for the UK of 50,000 genetically diverse cord blood units containing over 9 x 108 TNC.
Historically the NHS-CBB has banked donations containing more than 4 x 108 TNC. However, 89% of issued
units have a TNC counts exceeding 9 x 108. The NHS-CBB now banks cord blood units from Caucasian women
containing over 12 x 108 TNC and units from ethnic minority women containing over 9 x 108 TNC.
In addition to the 9 x 108 TNC minimum, stored cord units could also be classified under three different categories
in the inventory: A (TNC>18 x 108), B (TNC>13 x 108) and C (TNC<13 x 108). This categorisation would help
further determine the clinical value of a cord unit and the probability that it will be selected for transplantation.
Of 146 units shipped from the Programa Concordia in Spain, 53% were A category, 30% B category and 17% C
category cord units (S. Querol, personal communication to the review). The use of CD34+ counts (a more direct
measure of stem cell content) is an effective method to ensure the clinical effectiveness of stored units and should
be performed on all units, possibly to determine if they are suitable for banking.
Figure 13 Graphical depiction of the rationale and patient benefits of an optimised cord blood inventory for the UK.
100,000 donors
4/6 match : 99.6% (99% BME )
5/6 match : 86%(63% BME )
6/6 match : 41% (13% BME )
P
A
T
I
E
N
T
S
E
A
R
C
H
12.5 x10 8 TNC Threshold
80% probability of a median
of 9 5/6 matched units
Targeted (50%) BME collection:
71% match for whole population,
67% for BME patients
9.0 x10 8 TNC Threshold
75% probability of a median
of 6 5/6 matched units
50,000 donors
4/6 match : 98% (96% BME )
5/6 match : 80% (49% BME )
6/6 match : 34% (9% BME )
Targeted (30%) BME collection:
74% match for whole population,
52% for BME patients
10,000 donors
4/6 match : 95% (86% BME )
5/6 match : 64% (32%) BME )
6/6 match : 19% (3% BME )
Non-biased (15%) BME collection:
80% match for whole population,
36% for BME patients
Bank size
BME targeted collection
5.0 x10 8 TNC Threshold
69% probability of a median
of 3 matched units
Optimal
BME
Targeting of
30-50%
TNC Threshold
High Resolution Typing of Cord Blood Units
High resolution HLA typing of all banked cord blood units provides greater assurance to transplant centres
regarding the suitability of a HLA match between donation and patient. Currently, units stored at the NHS-CBB
are typed to low resolution.
A Report from the UK Stem Cell Strategic Forum July 2010
27
Annex 6
Supply Chain Options for Improving the Availability of Donor Stem Cells
in the UK
The Supply of Unrelated Adult Stem Cells
The supply of unrelated adult stem cells involves a series of activities depicted in Figure 14. Key activities are:
1. The recruitment of adult volunteer stem cell donors.
2. HLA typing of donor samples.
3. The registration of donor details on one of three UK registries: the ANT, BBMR and WBMDR.
4. A search for a suitable donor, instigated by a transplant centre.
5. Extended testing of donor samples to confirm suitability.
6. Donor counselling and consent.
7. The collection of peripheral blood stem cells or bone marrow.
The optimised supply of donor stem cells requires optimisation of this supply chain; these opportunities are
described further below.
Figure 14 Activities Involved in the Supply of Unrelated Adult Stem Cells
Key:
Key: EMDIS = European Marrow Donor Information System
EMDIS = European Marrow Donor Information System
28
Part 2: Annexes
The Role of UK Registries
During 2009, the three UK registries provided 791 donor stem cell donations for transplantation (WMDA, 2009).
41% of donations were sourced from UK donors; of these 72% were provided by the ANT, 27% by the BBMR
and 1% from the WBMDR. During 2009, 59% of donations were imported; of these 97% were imported by the
ANT and 3% by the WBMDR (the BBMR does not import) (Figures 15, 16 and 17).
Figure 15 The proportion on stem cells sourced from UK and overseas donors
Figure 16 The proportion of domestically-sourced stem cell donations provided by the three UK registries
Figure 17 The proportion of imported stem cell donations sourced via the ANT and WBMDR
A Report from the UK Stem Cell Strategic Forum July 2010
29
The Performance of UK Registries
The majority of imported stem cell donations are derived from Germany (ZKRD registry) and the USA (Figure 18).
Figure 18 Countries supplying stem cell donations to the UK
Using the ZKRD as an exemplar of a registry preferentially used by transplant centres, it can be seen that UK
registries operate less efficiently. According to WMDA data (WMDA, 2010), 57% of search requests handled by
the ZKRD registry result in the provision of a stem cell donation. This compares with a 15% conversion rate for
the ANT, 3.6% by the BBMR and 1.4% by the WBMDR. A contributory factor to the success of the ZKRD registry
lies in part with short times taken to provide donor samples to transplant centres, and for the registry to complete
extended donor typing (Table 5). In addition, relatively few German donors decline to donate at final work-up
compared to UK registries.
Table 5 Comparison of UK registry performance with the ZKRD registry in Germany
% donor samples
provided within 14 days
% extended donor types
within 14 days
30
29
58
68
24
27
96
69
ANT
BBMR
WBMDR
ZKRD
% donors declining to
donate at final ‘work up’
8
12
27
3
Opportunities to Improve the Supply of Stem Cells from UK Donors
Operationally, there are several opportunities to improve the efficiency and effectiveness of UK stem cell registries.
Donor Recruitment and Sampling
A primary opportunity is to improve the focus on the recruitment of donors from Black and ethnic minority
populations in the most cost effective manner. This might be best achieved by co-ordinating the efforts of
the ANT, blood services and third sector organisations. Each has different strengths. The ANT has a strong,
trusted and recognised brand with the public in addition to well developed systems for public engagement and
campaigning. In contrast, the UK Blood Services have an established infrastructure including blood donor venues
and extensive logistics. Third sector organisations have a distinct ability to engage directly with different BME and
religious communities, to engage volunteers, and to play a major role in education. The Forum took evidence
from third sector organisations such as the African Caribbean Leukaemia Trust, The Cord Blood Charity and
‘Register and be a Lifesaver’ (Annex 12). The latter organisation presented data on the effectiveness of presenting
information on the importance of donation to over 8000 students. Figures 19 and 20 summarise the changes
in students’ preparedness to donate before and after the presentation. It is noticeable that BME students are
particularly receptive to information on the importance of donation.
30
Part 2: Annexes
Figure 19 The changes in attitude of all students receiving a presentation on the importance of donation (source: Keith
Sudbury presentation to the UK Stem Cell Strategic Forum)
Figure 20 The changes in attitude of BME students receiving a presentation on the importance of donation (source: K.
Sudbury presentation to the UK Stem Cell Strategic Forum)
Donor Typing and Donor Provision
Opportunities to improve the effectiveness of UK stem cell registries include the consolidation of registry
databases, and the introduction of high resolution typing of selected donors and new registrants. The rationale
for high resolution typing is considered at Annex 4. The preferred approach would be to retrospectively type to
high resolution 75,000 selected donors over 3 years representing 36% of donors aged between 18 and 35, who
have been on a UK panel for more than 2 years. This approach, which is consistent with the need to develop a ‘fit
panel’ as described above will:
• reduce the time taken to provide donors, in this way reducing the number of patients who fail to receive a
transplant due to disease progression
• provide increased assurance to transplant centres that a donor will be an allelic match for the patient
• provide HLA allele-level information on the registry population of 750,000 donors in this way increasing the
predictive reliability of enhanced matching algorithms.
• allow the UK to ‘compete’ with other international registries for the ‘export’ of stem cell donors, and to
generate revenue as a result.
A Report from the UK Stem Cell Strategic Forum July 2010
31
Donor provision might be made more efficient by combining the activities of the three UK registries. This would
reduce effort on behalf of transplant centres who currently search different registers providing service levels.
An important aspect of donor provision is the provision of clinical advice on the suitability of potential donors.
A ‘graft identification advisory service’ (GIAS) is provided by the ANT. Regional NHSBT H&I laboratories provide
a similar service to the transplant centres they support. As noted above, a consolidated database accessed by
a single donor-providing organisation provides for the rationale application of high resolution typing combined
with the use of an enhanced matching algorithm programme such as those currently used by the ZKRD registry
(OptimatchTM) and the NMDP (HaplogicTM).
The Supply of Cord Blood Donations for Transplantation
The supply of cord blood for transplantation involves a series of activities depicted in Figure 21. Key activities are:
1. The consent of pregnant women and the collection of cord blood units
2. Donation assessment and HLA typing
3. Donation registration
4. Processing and cryogenic storage
5. Donation selection and issue
The optimised supply of cord blood units requires optimisation of this supply chain; these opportunities are
described further below.
Figure 21 Activities involved in the supply of cord blood at the NHS-Cord Blood Bank
There are currently 4 cord blood banks in the UK. These are summarised at Table 6.
Table 6 Summary of UK cord blood banks*
NHS-CBB
ANT
SNBTS
NIBTS
Banked donations
15,500
157
130
850
Donations available
for registry search
12,435 (BBMR)
0
0
850 (BBMR)
Number issued
309
0
0
1
Collection
5 hospitals in
London
3 hospitals in
London
1 hospital in
Glasgow
2 hospitals in
Belfast
*as at June 2010
32
Part 2: Annexes
The NHS Cord Blood Bank
The NHS Cord Blood Bank commenced banking in 1996; it has an inventory of over 15,500 units stored at
NHSBT’s Centre in Filton, Bristol. The Filton Blood Centre, opened in 2008 at a cost of over £60m, has capacity for
up to 100,000 units, a suite of 4 clean rooms and extensive laboratory capacity undertaking a range of diagnostic
and translational research activities. The NHS-Cord Blood Bank collects from 5 hospitals in the London area and
has provided 309 units for transplantation (as at June 2010).
The Anthony Nolan Cord Blood Bank
The Anthony Nolan has developed from its pioneer beginnings as the world’s first Register of unrelated bone
marrow donors into one of Europe’s leading providers of stem cell donations for clinical use. In addition to
this clinical activity, the ANT has developed a base of core research capability into improving the outcomes of
haemopoietic stem cell transplants, whilst also collaborating on the development of new stem cell therapies with
partners in Europe and beyond. In line with these strategic drivers, the ANT has established a comprehensive cord
blood collection, banking and research programme.
The ANT started importing cord blood units for transplantation to UK patients in 2002 and has experienced
increasing demand to the point where the ANT is now importing over 80% of the clinical cord units used annually
in the UK. In recognition of this growing need for good quality clinical use cord blood units, the ANT established
in 2008 a new state of the art cell therapy centre in Nottingham that combines both a cord blood bank and cord
blood research facility with an investment of over £5 million. Using the latest collection and processing techniques
and employing leading experts in the field, the ANT is now able to start providing high quality cord blood units to
UK transplant centres at less than half the cost of leading US cord banks.
The Charity’s current annual investment of just over £1.3 million per annum covers the operational costs of the
Anthony Nolan Cell Therapy Centre, a collection unit at King’s College Hospital and two new collection units at
Leicester General Hospital and Leicester Royal Infirmary. This investment will increase significantly from 2010/11
with the addition of two further large volume collection units in order to allow the ANT to reach an initial target
of 15,000 high grade clinical cord blood donations by 2015. This cord blood unit inventory will complement the
adult donor register and enable the ANT to get much closer to its target of doubling the number of patients
provided with donors for each day. In addition during the same period the ANT expects to collect approximately
18,000 research suitable cord units, which the research tissue bank will use and direct into basic and translational
research for cord blood transplantation and further stem cell therapies.
The SNBTS Cord Blood Bank
SNBTS has been funded by Scottish Government Health Department (SGHD) for several years to establish a
cord bank, with a capital investment of £244K. The initial size of the bank based on historical discussions at UK
level was 3000, a proportionate share of the original UK target of 30,000. All of the physical infrastructure has
been in place for several years. A clean room for processing has also been provided although this has now been
superseded by closed system technology. All validations are now complete. SNBTS has an existing HTA licence and
this will be extended shortly to include cord banking. Scotland has extensive research interests in cellular therapy
and regenerative medicine funded through, amongst others, SGHD, Scottish universities, Scottish Enterprise and
the Medical Research Council (MRC). Of particular note is the MRC Scottish Centre for Regenerative Medicine
(SCRM). SNBTS activities in stem cells and cellular therapy are integral to this research effort with SNBTS carrying
out original research generating novel therapies for clinical trial and providing quality and regulatory support
to the SCRM and to Roslin Cells (a not for profit company funded by Scottish Enterprise to make current good
manufacturing practice (cGMP) stem cell lines). SNBTS strategy is to integrate all of its current infrastructure and
resources in a new National Centre to consolidate and extract synergies in cellular therapy including cord banking,
stem cell processing, islet cell processing, and translational cell therapy research e.g. corneal epithelial stem cells.
Cord blood banking is integral to this process.
A Report from the UK Stem Cell Strategic Forum July 2010
33
The NIBTS Cord Blood Bank
The Northern Ireland Blood Transfusion Service (NIBTS) commenced banking in 2003; units are registered with
the BBMR. Cord blood units are collected from two hospitals in Belfast, and mothers are consented in accordance
with HTA (Human Tissue Authority) Codes of Practice. The NIBTS Cord Blood Bank has an inventory of 850 units,
and has issued one unit (to Brazil).
Increasing the Utilisation of Cord Blood Banked in the UK
The importance of stem cell dose in determining post-transplant outcomes is considered in Annex 5. From 1997,
when the NHS-CBB commenced operations, to May 2010, the bank selected for cryopreservation units containing
over 40 x 107 TNC. After May 2010, the NHS-CBB cryopreserved units from BME donors containing over 90 x 107
TNC, and units from Caucasian donors containing over 120 x 107 TNC. The TNC profile of banked units is shown
in Figure 22.
Figure 22 Composition of cord blood units at the NHS-Cord Blood Bank
3500
3000
No. Donors
2500
Key.
Ethnic minority units
Caucasian units
2000
1500
1000
500
0
40-65
65-90
90-120
120-150
>150
TNC (*10^7)
In contrast to this profile, the majority of units issued from the bank contain over 150 x 107 TNC. This profile is
shown at Figure 23. Currently, approximately 0.3% of the NHS-CBB inventory is issued per annum, although
utilisation of high dose units is circa 0.8%.
These data suggest that patients’ needs are best met by banking only those units containing over 90 x 107 TNC.
Additionally, all cord blood units containing over this threshold should be typed to high resolution for HLA-DR to
assist transplant units in selecting the best unit for patients. Taken together, these changes should result in better
overall utilization of cord blood units banked in the UK.
Key.
Ethnic minority units
Caucasian units
No Issued
Figure 23 Profile of cord blood units issued from the NHS-Cord Blood bank
180
160
140
120
100
80
60
40
20
0
40 - 65
34
Part 2: Annexes
65-90
90-120
TNC (x10^7)
120-150
>150
Increasing the Genetic Diversity of Banked Cord Blood Units; Managing the Expectations of
Those Wanting to Donate
The models of cord blood inventories described above show that the needs of UK patients are best met by
banking 30% to 50% of cord blood units from Black and ethnic minority donors. Since 45% of ethnic minority
individuals live in and around London (Figure 24), it follows that an ethnically diverse cord blood inventory may
best be achieved by collecting cord blood units primarily from London hospitals with maternity units with over
5000 births per annum. The NHS-CBB currently collects cord blood from 5 London hospitals; 39.5% of donations
are from ethnic minority donors. An inventory of 50,000 banked units over 90 x 107 TNC could be achieved over
an 8 year period by collecting cord blood from 25 - 30% of women attending around 13 hospitals (Annex 7).
The need to collect cord blood units as cost effectively as possible should be balanced against the desire of some
women in all parts of the UK to donate. Logistically, maternity units collecting cord blood are best managed in
clusters, allowing staff to move from hospital to hospital to ensure 24/7 attendance to maximise the number of
units collected. While further work is required to determine optimal locations, it may be appropriate to establish a
cluster of hospitals in the north-west of England, as well as some collection in Northern Ireland and Scotland.
Figure 24 Distribution of ethnic minority individuals in the UK (UK Census data, April 2001)
Key.
6.4% to 60.4%
2.5% to 6.3%
1.5% to 2.4%
1.0% to 1.4%
0.2% to 0.9%
A Report from the UK Stem Cell Strategic Forum July 2010
35
Annex 7
Financial Appraisal of Options to Reconfigure the Supply Chains
Methodology
The UK currently hosts three stem cell registries and four cord blood banks. These all undertake a variety of
processes, from recruitment/collection and registration/storage to typing and shipping. In delivering an expanded
cord inventory and a fit panel, a number of different service frameworks are possible. To assess different options
to increase the supply of donor stem cells, and to improve cost effectiveness, the costs associated with existing
activities were determined. Costs were based on actual 2009 expenditure and an activity-based costing model
applied to apportion costs to different drivers with supply chains. Cost projections were lower for consolidated
models with a single registry and a unified cord inventory.
The Current Cost of Providing Unrelated Adult Stem Cells to UK Patients
The total cost of providing unrelated adult stem cells for UK patients was £25.4m during 2009 (Table 7). This
includes organisational overheads, infrastructure costs as well as direct costs, and the cost of importing stem cell
donations (ANT importation costs of £8.75m). Scottish donors are registered with the ANT. Northern Irish donors
are registered on the BBMR.
Table 7 Registry costs for the provision of unrelated adult donor stem cells. Costs shown are actual expenditure for 2009/10.
Registry
ANT
BBMR
WBMDR
NIBTS
UK TOTAL
Stem Cell Provision Costs
(2009/10)
£18.91m
£4.84m
£1.62m
£0.03m
£25.41m
The average cost of providing each unrelated adult stem cell donation was circa £26K during 2009 (Table 8).
Table 8 Key performance indicators for unrelated donor stem cell provision
Activity
Recruitment to registration (per newly registered donor)
Registry management (per donor on registry)
Donor provision (per completed donation)
Supply chain (per completed donation)
36
Part 2: Annexes
Unit Activity
35,482
763,409
970
970
Cost/Unit (£)
150
1
19,993
26,196
Figures 25, 26 and 27 shows, at a high level, the cost profiles for unrelated adult stem cell supply by the three
UK registries. The analysis shows the low cost of BBMR donor recruitment (around 12,000 donors per annum)
compared to the ANT (around 16,000 donors per annum). This reflects the ‘passive’ approach taken by the BBMR,
which registers donors presenting at blood collection clinics. The ability of the BBMR to type more than 12,000
donors per annum is restricted by the level of grant in aid funding provided for this activity. The analysis shows
that donor typing costs are largely variable; this reflects high cost of reagents. The costs of donor provision reflect
the different activities of the registries.
Figure 25 The cost profiles of unrelated adult stem cell supply chains by the BBMR
Key:
Fixed costs
Step fixed costs
Variable costs
Figure 26 The cost profiles of unrelated adult stem cell supply chains by the ANT
(Note: ANT costs for donor registration and registry management are combined with donor recruitment and sample
collection costs.)
A Report from the UK Stem Cell Strategic Forum July 2010
37
Figure 27 The cost profiles of unrelated adult stem cell supply chains by the WBMDR
The Current Cost of Providing Cord Blood to UK Patients
The total cost of providing cord blood donations for UK patients was £7.99m during 2009 (Table 9). This includes
organisational overheads, infrastructure costs as well as direct costs, and the cost of importing cord blood
donations (ANT importation costs of £2.1m). Scottish donors are registered with the ANT. Northern Irish donors
are registered on the BBMR.
Table 9 Organisational costs for the provision of cord blood donations. Costs shown are actual expenditure for 2009/10.
Organisation
ANT
NHS-CBB
SNBTS
NIBTS
UK TOTAL
Cord Blood Provision
Costs (2009/10)
£2.98n
£4.16m
£0.62m
£0.23m
£7.99m
The average cost of providing each cord blood donation was circa £71K during 2009 (Table 10). However, this
reflects the upfront expansion costs of collection and storage for cord units that will have an expected lifecycle of
20 years. The long term steady state cost of a cord in an adequately sized inventory with good utilisation would
only be a fraction of this (Annex 8).
Table 10 Key performance indicators for cord blood provision
Activity
Recruitment and processing (per addition to bank)
Storage (per banked cord)
Issue (per issues)
Supply chain (per issue)
38
Part 2: Annexes
Unit Activity
2,624
12,677
112
112
Cost/Unit (£)
1,740
67
23,045
71,352
Figures 28, 29, 30 and 31 show, at a high level, the cost profiles for cord blood supply in the UK. The analysis
shows the high fixed cost associated with cord blood banking. ANT costs include import activity.
Figure 28 The cost profiles of cord blood supply, NHSBT
NHSBT Cord Blood Supply Chain
2,500
2,000
£000's
1,500
Key:
1,000
500
Fixed costs
0
Recruitment &
Collection
Step fixed costs
Variable costs
Evaluation,
Typing, Testing,
Processing
Registration and
Registry
management
Donor provision
(excl. Import)
Donor Provision
(import)
Supply Chain Activity
Figure 29 The cost profiles of cord blood supply, ANT
ANT Cord Blood Supply Chain
2,500
2,000
£000's
1,500
1,000
500
0
Recruitment &
Collection
Evaluation,
Typing, Testing,
Processing
Registration and
Registry
management
Donor provision Donor Provision
(excl. Import)
(import)
Supply Chain Activity
Figure 30 The cost profiles of cord blood supply, SNBTS
SNBTS Cord Blood Supply Chain
2,500
2,000
£000's
1,500
1,000
500
0
Recruitment &
Collection
Evaluation,
Typing, Testing,
Processing
Registration and
Registry
management
Donor provision Donor Provision
(excl. Import)
(import)
Supply Chain Activity
A Report from the UK Stem Cell Strategic Forum July 2010
39
Figure 31 The cost profiles of cord blood supply, NIBTS
NIBTS Cord Blood Supply Chain
2,500
2,000
£000's
1,500
1,000
500
0
Recruitment &
Collection
Evaluation,
Typing, Testing,
Processing
Registration and Donor provision Donor Provision
Registry
(excl. Import)
(import)
management
Supply Chain Activity
Supply Chain Options
Future stem cell costs and associated health economic benefits (see Annex 8) will be determined in part by the
service framework within which adult stem cells and cord blood units are delivered. Four broad supply chain
models were considered by the Strategic Forum, involving various degrees of consolidation or dispersal of service
provision. These are summarised in Table 11.
Table 11 Four options for the supply of adult stem cell and cord blood donations.
Activities & Assumpti
on
Option 1
Consolidation
Option 2
Option 3
Consolidate
No
Registries only Consolidation
Registry
Donor recruitment
Donor communications
High resolution typing
Advanced matching
algorithm
Donor provision
activities & clinical
advice
Cord Blood Bank
Cord blood collection,
testing, high resolution
typing, banking, issue.
50,000 high dose units
after 8 years, 1%
utilisation (except
option 4).
1 UK registry
1 UK registry
3 UK registries 3 UK registries
Donor
recruitment via
ANT, third
sector & 4
blood services.
Donor
recruitment via
ANT, third
sector & 4
blood services.
Donor
recruitment via
ANT, third
sector & 4
blood services.
Donor
recruitment via
ANT, third
sector & 4
blood services.
1 UK CB bank
4 CB banks
SNBTS - 6000
NIBTS - 3000
ANT - 20,000
NHS-CBB 21,000
4 CB banks
SNBTS - 6000
NIBTS - 3000
ANT - 20,000
NHS-CBB 21,000
4 CB banks
SNBTS - 6000
NIBTS - 3000
ANT - 4,000
NHS-CBB –
20,000
•
•
•
•
•
•
40
Part 2: Annexes
Single bank of
50,000
Option 4
Status Quo
(no additional
funding)
The Cost of Adult Stem Cell Provision
The UK has a combined panel exceeding 770,000 donors (WMDA, 2010). Further expansion would bring only
marginal gains, and at considerable expense. To maximise patient benefits, service providers should concentrate
instead on quality improvements. The creation of a ‘fit panel’ of high resolution typed, readily available donors would
be an effective strategy to achieve this (Annex 4). This report commends the following strategy to achieve this:
• High resolution typing - retrospective high resolution typing would be performed on 36% (75,000) of
registered donors aged between 18 and 35 years, over a three year period. This would cost £67.70 per type.
• Regular communication with volunteers - all 750,000 registrants would be contacted at least annually to
confirm their willingness to donate, their contact details and current state of health. This would cost £0.30 a
contact (i.e. £0.23m per annum), with additional contact online and via e-mail at no additional cost as this is
already being practised by the ANT. Furthermore, in the first three years, it will be necessary to contact those in
the target groups by telephone to invite them for high resolution typing and make sure they are still willing to
donate. This is estimated to cost £7 per contact, so £0.17m per annum for three years.
• Graft Identification Advisory Service (GIAS) - an advisory service on donor/donation suitability would be
offered. This is already being piloted by the ANT.
• Predictive search technologies - donor search queries would be facilitated by a computer programme such
as Haplogic or Optimatch. The costs this would involve are currently unknown.
The following assumptions were made in estimating registry costs:
• Export income, inflation costs and VAT increases (after June 2010) have been excluded;
• The costs of high resolution typing (options 1, 2 and 3; years 1 to 3) and increased donor communications (see
above) are included;
• The current cost base for the 4 registries has been applied to the recruitment of unrelated donors;
• The consolidated registry options (options 1 and 2) assume that fixed costs associated with two registries can
be removed. Further scope for further efficiency savings against variable and stepped fixed costs should be
achieved;
• Any increase in registry utilisation following consolidation and high resolution typing has been excluded;
• In option 4 (status quo), it is assumed that current expenditure levels are maintained without investment to
achieve a ‘fit panel’.
Table 12 sets out the cost of developing the provision of unrelated adult stem cells in the UK; costs are shown
over an eight year period for the four options set out at Table 11.
The cost of an adult stem cell donation is estimated to be circa £28K when provided from a consolidated registry,
and circa £30K when provided from via three UK Registries. This incremental increase reflects the additional fixed
costs associated with multiple registries.
A Report from the UK Stem Cell Strategic Forum July 2010
41
42
Part 2: Annexes
Table 12 Total adult donor stem cell chain costs
The Cost of Cord Blood Provision
Table 20 summarises the cost of expanding the UK’s cord blood inventory to 50,000 units over eight years; these
estimates are based on the NHSBT’s full activity-based cost model (an activity-based analysis of collection, banking
and issue costs over 10 years). Alternative costs were provided by the ANT during the course of the Review to
collect and bank 20,000 units over 5 years; these are set out below.
In estimating the costs set out at Table 20, the following assumptions and data sources were used:
• NHSBT activity-based costing model;
• A cord bank inventory utilisation rate of 1% over 8 years;
• Income from export, inflation effects and VAT increases post June 2010 were excluded;
• NHSBT activity data regarding the efficiency of the cord blood supply chain were used:
• 30% of recruited donors result in a cord blood collection;
• 32.8% of collections contain sufficient TNC for banking for clinical use;
• Variable costs were flexed in line with activity;
• Stepped fixed costs were flexed in line with capacity break points.
• Incremental collection staff costs were based on 13 London-based maternity units managed in geographical
clusters to maximise shift coverage;
• Incremental laboratory cost were based on throughput analyses for typing, processing and issue activities;
• Fixed costs were based upon NHSBT costs. For options 2 and 3 (4 UK cord blood banks) ANT fixed costs were
assumed to match current NHSBT costs (comparable banking targets); NIBTS and SNBTS fixed costs were
assumed to 50% those of NHSBT due to smaller banking targets.
• For options 2 and 3 (4 UK cord blood banks) variable and stepped fixed costs were assumed to have similar
profiles across the four providers.
• Option 4 (status quo) assumes that NHSBT collection and banking activities cease once the current target of
20,000 units is reached.
Table 13 shows that, given the assumptions detailed above, the cost of developing a UK inventory of 50,000
units is between £78.1m (consolidated cord blood bank) and £103.1m (four UK cord blood banks). After 8 years,
the cost of a cord blood unit from a consolidated UK inventory is estimated to be circa £16K per unit. The cost
of a cord blood unit is estimated to be circa £22K when provided from 4 UK cord blood units. This incremental
increase reflects the additional fixed costs associated with 4 suppliers. The cost per unit rises to circa £48K per
unit after 8 years in the absence of funding to improve the quality of the inventory and utilisation rate.
A Report from the UK Stem Cell Strategic Forum July 2010
43
44
Part 2: Annexes
Note These estimates are based on the NHSBT cost profiles; an alternative estimate to bank 20,000 units (each over 9 x 108 TNC) over 5 years has been provided by the
ANT and is described below.
Table 13 Total adult donor stem cell chain costs
The Anthony Nolan Trust has estimated the cost of building a cord blood bank of 20,000 units over 5 years
(£29.0m). These costs are set out at Table 14. These costs equate to circa £1,450 per banked unit compared to
£1,700 per banked unit using NHSBT costs. Further work is required to understand differences between the two
costing models.
Table 14 Anthony Nolan Trust costs to collect and bank 20,000 cord blood units.
A Report from the UK Stem Cell Strategic Forum July 2010
45
Annex 8
Health Economic Analysis
Summary
A health economic cost-benefit analysis shows that the case for developing a fit panel and expanding the
inventory of cord blood units to 50,000 in the UK looks broadly reasonable. Drawing on published literature on
survival outcomes and detailed cost breakdowns from provider organisations, the necessary investment costs of
a ‘fit’ panel appeared from a preliminary analysis to be fully recoverable through increased utilisation and service
efficiency, such as fewer unsuccessful searches, though a number of gains and costs have not been quantified
at this stage. To achieve a 50,000 unit cord inventory, the incremental costs of expansion per Quality-Adjusted
Life Year (QALY) are in the region of £27K, typically considered to be justifiable in the context of public health
spending. This would depend on an annual utilisation rate of 1% per annum, a feasible target consistent with
other larger banks worldwide.
At this rate, the cost of cord blood transplantation is estimated to be less than adult donor stem cell
transplantation within 4 years for a single unit transplant and within 7 years for a double unit transplant. The
greatest area of uncertainty is in respect to patient outcomes: there is currently limited information on long-term
survival and quality of life following stem cell transplantation. However, as HSCT practice improves and survival
rates rise further, the economic case for investment in cord blood banking and unrelated donor registries is likely
to improve.
QALY Life Gains following Unrelated Stem Cell Transplantation
In developing a plausible framework for implementing a stem cell strategy in the coming decade, it is necessary
to gain a clear idea of the incremental costs that accompany various service models. For the sake of patients, it
is essential that finite resources are channelled as efficiently as possible to ensure that services represent ‘value
for money’ in terms of clear health care benefits. Though part of the focus of these discussions is financial, the
central consideration is the patient and the possible improvement in both survival and quality of life that he or she
receives.
In gauging the benefits of unrelated donor transplantation, the standard measurement is the Quality-Adjusted
Life Year (QALY). The purpose of the QALY is to provide a more nuanced picture of the value of HSCT by
considering not only the net gains in terms of overall survival, but also the improved quality of life it may bring to
the patient. This involves a range of factors and varies considerably. The QALY analysis for this review draws on
recent international survival data for several of the most common HSCT-treatable conditions. These surveys drew
on large patient samples over an extended timeframe, with a general bias on adult donor transplants (Table 15).
Table 15 Literature review of survival rates
Paper
Bergstrom et al.
Costa et al.
Howard et al.
Bhatia et al.
(2008)
(2007)
(2005)
(2007)
AML, ALL
Any
AML, CML, ALL,
Conditions AML,CML, ALL,
MDS, NHL, AA
NHL, AA,
Age range
Not stated
Adults
Adults & children
Adults & children
Stem cells
BM
BM & CB
BM
BM & CB
Country
US
International
International
US
Years of
1987 - 2004
Meta analysis
1988 - 1996
1974 - 1998
Large
1,479
study
Size
Large
Meta analysis
Key:
AA - aplastic anaemia
ALL - acute lymphoblasic leukaemia
AML - acute myeloid leukaemia
BM - bone marrow
CB - cord blood
CML - chronic myeloid leukaemia
MDS - myelodysplastic syndrome
NHL - non Hodgkin’s lymphoma
The transplant survival data in these studies has been integrated and benchmarked against
46
Part 2: Annexes
The transplant survival data in these studies has been integrated and benchmarked against an Office for National
Statistics (ONS) model of life expectancy based on historic mortality rates. The QALY gains associated with
transplantation have then been calculated by measuring the difference between the net QALY expectancy with or
without HSCT (Table 16).
From these results, average QALY values have been assigned to each age group, with a 1.5% discount rate per
annum. In summary, the QALY gains are higher for paediatric patients; the data range suggests a 5-8 QALY value
for children. This may be even higher for very young transplant patients (Howard et al. 2005). Among older age
groups, due to lower future life expectancy, QALY gains are significantly smaller. QALY gain is in the region of 3-4
for 30 year olds. QALY value per year was downgraded by a factor of 0.8 to reflect co-morbidities and ongoing
reductions in the patient’s health-related quality of life.
Nevertheless, despite the variations between the studies, the evidence confirms the value of HSCT as a lifeextending and life-enhancing therapy. In every disease category, alternative survival rates without HSCT are
inferior. This supports the application of HSCT as a suitable therapeutic option for selected patients.
Table 16 Source data used to determine QALY gains following unrelated donor stem cell transplantation.
Bergstrom et al (2008)
Stem cell Disease
Alternative
type
BM
AML
Chemotherapy
BM
CML
Chemotherapy
BM
ALL
Chemotherapy
BM
MDS
None
BM
AA
Immunosuppressive therapy
Costa et al (2007)
Stem cell Disease
Alternative
type
BM/PB
ALL/AML None
CB
ALL/AML None
Survival
data type
5 years
5 years
15 years
10 years
10 years
Survival
data type
5 years
5 years
Transplant
survival
45%
45%
68%
27%
45%
Transplant
survival
18.20%
14.40%
Alternative
survival
29%
30%
26%
2%
25%
Alternative
survival
1%
1%
Howard et al, IoM Report (2005)
Stem cell
type
8/8 BM
match
7/8 BM
match
CB
Disease
Alternative
ALL/AML
Chemotherapy
Survival
data type
5 years
ALL/AML
Chemotherapy
5 years
ALL/AML
Chemotherapy
5 years
Transplant Alternative
survival
survival
49% <20,
15%
36% >= 20
41% <20,
15%
25% >= 20
41% <20,
15%
25% >= 20
QALY gain
Age 10 Age 20 Age 30 Age 40 Age 50
4.81
4.49
12.03
8.37
5.9
4.17
3.9
10.46
7.41
5.14
3.44
3.22
8.73
6.32
4.28
2.61
2.44
6.97
5.13
3.36
1.78
1.66
5.37
3.98
2.49
QALY gain
Age 10 Age 20 Age 30 Age 40 Age 50
5.57
4.1
4.88
3.57
4.09
2.96
3.19
2.26
2.27
1.56
QALY gain
Age 10 Age 20 Age 30 Age 40 Age 50
10.54
5.6
4.64
3.55
2.45
8.02
2.54
2.09
1.57
1.05
8.02
2.54
2.09
1.57
1.05
A Report from the UK Stem Cell Strategic Forum July 2010
47
The Cost of Stem Cell Transplantation
HSCT is a complex procedure, requiring experienced personnel, well-resourced facilities and several highly
specialised drugs to support engraftment. In addition, the full costs of a transplant must include the postoperative management provided to the patient. Table 17 outlines the approximate costs of transplantation,
including stem cell procurement and post-HSCT care8. This has been calculated by adapting the methodology
used by van Agthoven et al. (2002) and drawing on unit costs provided by the PSSRU Unit Costs of Health
and Social Care 2009 database. Where these were not available, costs have been scaled and converted from
the original study. The costs of post-operative care have also been weighted to reflect the fact that, with every
progressive phase of treatment, a smaller proportion of transplanted patients are alive to receive it. Costs were
converted using 1999 pound / euro exchange rates and adjusted for 3% annual inflation in pay and prices. There
are a number of caveats. The non-UK data may have only limited applicability, and only includes unrelated adult
donor transplants, not cord HSCT. The patients are all adults and therefore paediatric patients are excluded.
Table 17 Summary of transplant costs per patient (extrapolated from van Agthoven et al. (2002)).
Average costs per
Weighted costs per
Component
living patient
% alive
transplant patient
Personnel
£31,409
100%
£31,409
Transplantation
£40,140
100%
£40,140
Follow Up 1
£29,713
90%
£26,742
Follow Up 2
£18,119
48%
£8,697
Follow Up 3
£13,075
31%
£4,053
Total Costs
£132,456
£111,041
This brings the total cost of transplant per patient to around £110,000. This approximates the current London
commissioning price of £101,000 per transplant.
However, this should be set against the often considerable costs of not transplanting a patient, such as ongoing
chemotherapy and supportive care. These costs have been estimated at around £20,000 per patient, though this
may fluctuate significantly from case to case.
The Current Cost of Providing Stem Cells for Transplantation
A significant proportion of the cost of unrelated donor HSCT is the costs of procuring suitably matched stems for
patients. This in turn reflects the accumulated costs of each individual step in the process chain, from recruitment/
collection and registration/storage to shipping / issue.
Registries and cord banks are collective resources with low lifetime utilisation rates: only a fraction of adult
volunteers and listed cord blood donations will ever be used for transplantation. The true procurement costs of
every stem cell sample used in HSCT must therefore include a share of the total costs associated with the other
adult donors or cord units that are recruited or collected, typed, listed and searched without ever being selected
by transplant physicians. This means that the true cost of each stem cell donation far exceeds the specific costs of
the selected donor or cord unit. Consequently, the overall costs of bone marrow (Table 18) and cord blood (Table
19) are weighted to reflect this.
8 The figures have been modelled using data on the five most frequent conditions treated with allogeneic HSCT: acute lymphoblastic leukemia (ALL), acute
myeloid leukemia (AML), chronic myeloid leukemia (CML), non-Hodgkin’s lymphoma (NHL), aplastic anaemia (AA) (D. Pamphilon, personal submission to the
Review; Bhatia et al. 2007).
48
Part 2: Annexes
This results in distinct costing dynamics for the UK’s donor registries and cord blood banks. Though the assumed
lifecycles of volunteer donors and cord units are similar, in the region of 20 years, donor registries generally have
much lower lifetime utilisation rates than cord blood banks. Compared to NHS-CBB’s current utilisation rate of
0.3% and the >1% utilisation rates of some international banks, the BBMR has an annual utilisation rate of
around 0.05%9. Consequently, donor registries are generally much larger than cord blood banks. This means that
the processing costs for multiple unselected donors must be factored in to the real cost of every selected donor.
These may be one-off costs such as donor typing and testing, with an average of 105 donors processed for every
donor selected: this reflects the likely 1% lifetime utilisation rate of an individual donor. Other costs, such as
registry maintenance, are continuous and have to be spread out across the entire panel, meaning that a selected
donor will carry weighted costs amounting to an average of 2,082 years on the panel: this reflects the proportion
of listed donors to every sample issued over the course of a year. Balancing the large volume of donors on the
registry, however, is the generally low process costs associated with adult volunteers. The most substantial costs
are for extended typing, donor work up and harvesting, but these are only performed once the donor has been
identified as a suitable match and therefore involves relatively little weighting (extended typing) or no weighting
at all (donor work up and harvest) (Table 18). Overall, the weighted current long term cost for a bone marrow
donation is around £36K.
Table 18 Current long run costs of providing unrelated adult stem cells for transplantation
Component
Cost/Event Events per
Transplant
Weighted Cost per
Transplant
Donor recruitment & sample collection
£12.90
105
£1,349
Donor typing & testing
£107.15
105
£11,207
Donor registration
£1.56
105
£164
Maintenance of donor panel
£2.31
2,082
£4,817
Registry search
£13.82
51
£701
Ship confirmatory samples
£567.18
7
£3,861
Perform extended typing
£1,313.86
3.7
£4,814
Donor work up
£3,838.13
1.0
£3,838
Donor harvest
£5,464.76
1.0
£5,465
Follow up
£308.07
0.8
£253
Total current long run cost per issued donation
£36,469
Cord blood banks are generally smaller, with much higher utilisation rates: the NHS-CBB currently operates with
a 0.3% annual utilisation rate. The weighting for the true cost of an issued cord unit in the UK is therefore much
smaller. One-off costs such as typing and testing are performed on around 15 cord blood donations for every
selected unit, while continuous costs such as bank maintenance, distributed across the entire inventory, require
298 events for every transplant – a much smaller proportion than is required for donor registries. Nevertheless,
these processes generally carry a much higher individual cost for cord than with adult volunteers. Ultimately, this
means that the real cost of an issued cord unit is at present higher than an adult donation. Overall, the current
long term cost for every cord blood unit issued from the NHS-CBB is circa £45K.
9
According to NHSBT data, donors registered with the BBMR have a lifetime utilisation rate of 0.96% (NHSBT, 2010).
A Report from the UK Stem Cell Strategic Forum July 2010
49
Table 19 Current long run costs of providing cord blood units for transplantation
Component
Cost/Event
Events per
Transplant
Weighted Cost
per Transplant
CB recruitment & sample collection
£292.36
21
£6,139
CB evaluation
£43.19
21
£907
CB typing & testing
£244.23
15
£3,757
CB processing
£281.63
15
£4,332
CB registration
£160.51
15
£2,469
Maintenance of CB bank
£51.94
298
£15,479
Perform extended typing
£997.26
4
£4,378
Final product evaluation
£6,688.11
1.0
£6,688
CB issue
£472.44
1.0
£472
Total current long run cost per issued donation
£44,622
Cost-Benefit Analysis – Establishing a Fit Stem Cell Registry Donor Panel
The UK already has a combined panel exceeding 770,000 donors (WMDA, 2010). Further expansion would
bring only marginal gains, and at considerable expense. To maximise patient benefits, service providers should
concentrate instead on quality improvements. The creation of a ‘fit panel’ of high resolution typed, readily
available donors would be an effective strategy to achieve this (Annex 4).
In consultation with clinicians and operational managers through the Review, the following framework was
developed as a feasible strategy to implement the fit panel:
• High resolution typing - retrospective high resolution typing would be performed on 36% (75,000) of
registered donors aged between 18 and 35 years, over a three year period. This would cost £67.70 per type.
• Regular communication - all 750,000 registrants would be contacted at least annually to confirm their
willingness to donate, their contact details and current state of health. This would cost £0.30 a contact (i.e.
£0.23m per annum), with additional contact online and via e-mail at no additional cost as this is already
being practised. Furthermore, in the first three years, it will be necessary to contact those in the target groups
by telephone to invite them for high resolution typing and make sure they are still willing to donate. This is
estimated to cost £7 per contact, so £0.17m per annum for three years.
• Graft Identification Advisory Service (GIAS) - an advisory service on donor/donation suitability would be
offered. This is already being piloted by the ANT.
• Predictive search technologies - donor search queries would be facilitated by a computer programme such
as Haplogic or Optimatch. The costs this would involve are currently unknown.
50
Part 2: Annexes
Together, these measures introduce an incremental cost on a current baseline of £2.2m per annum for the
first three years then £0.3M per annum subsequently. This does not include the associated costs of GIAS and
predictive search technologies: these have not yet been quantified and so are not at this stage factored into the
calculations.
The benefits of this panel would include:
• Fewer unsuccessful searches - registered donors available to donate will increase from circa 60% to 90%.
Based on there currently being 25,781 searches at £18.13 each, and the number of searches being reduced by
around 1/3, this should bring savings of £0.14m per annum.
• Fewer extended typings per final donation - almost 4 extended typings are currently undertaken for every
transplant, at £373 each. With a fit panel, this should reduce to 1 extended typing per transplant.
• Shorter search-to-transplant times - the average time from search initiation to transplant would reduce by
an average 4 to 6 weeks (D. Marks, personal communication to the review). This would result in less patient
deterioration, less inpatient and outpatient resource, resulting in cost savings to the NHS (not quantified).
Reduced search-to-transplant times would also improve quality of life for patients. This would bring in an
estimated 0.4 QALY gain for 300 patients over 4 to 6 weeks, translating to a benefit of £0.55 million per
annum.
Together, these measures result in an estimated quantified benefit from a fit panel of approximately £1.0m per
annum. In summary, this preliminary cost-benefit analysis shows that the fit panel proposals look promising, with
an incremental cost of circa £9m balanced against £9m gain over a 10 year horizon. However, other significant
costs and benefits remain to be evaluated. These include the costs of GIAS and the search algorithm, as well as
the improvement in survival outcomes from shorter search-to-transplant times and reduced chemotherapy toxicity.
The results should be verified when the currently ongoing GIAS pilot is completed, and further work is done to
evaluate the overall costs and benefits.
An Expanded UK Cord Blood Inventory
When designing a UK inventory, a number of factors should be considered. These include:
• Size – the size of the inventory. A larger inventory will have higher costs, but may be more efficient in terms of
per unit costs as the fixed costs and overheads are shared across a greater number of units.
• Annual utilisation – the proportion of an inventory’s stored units issued every year. In principle, utilisation
rates may fall as the size of an inventory increases, but in reality this relationship is more complex. Utilisation is
one of the key determinants in whether a cord inventory is economically feasible.
• Ethnicity – the racial composition and diversity of its stored units. Cord blood has a particular role to play in
reducing current levels of unmet need. However, considerable Caucasian demand for cord also exists.
Size
The optimal size of a cord inventory is one of the central considerations in its design. Clearly, the overall
operational costs of a smaller cord inventory are likely to be less than for an expanded inventory. In theory, in the
context of limited patient demand, a smaller bank should issue a higher proportion of its stored units every year,
even if the actual number of units is lower. In reality, the relationship between size and utilisation is not so clear
cut. This is discussed in more detail below.
Despite incurring greater overall costs, a larger inventory may prove more economic due to the significant
portion of fixed overheads in staff, equipment and infrastructure. While many of the costs of adult donations are
associated with donor identification and extraction, processes only undertaken once the donor has already been
selected for transplantation, with cord blood the majority of the costs such as collection and storage are upfront
and carried out regardless of whether or not they are issued. Expanding the size of the UK’s cord inventory
could therefore reduce the individual share of that fixed cost per unit, provided a reasonable utilisation rate was
maintained.
A Report from the UK Stem Cell Strategic Forum July 2010
51
Secondly, an inventory requires a ‘critical mass’ of cord units to operate effectively as a patient-oriented service
and justify its investment. An expanded inventory should have a broader range of HLA types and can therefore
provide a greater number of patients with a match. Up to a point, this may raise its number of issued units
sufficiently to maintain an acceptable utilisation rate. As its size increases, however, this may be undermined by
replication as stored cord blood donations begin to ‘overlap’ with the HLA type of other units in the inventory and
increasing number of stored units become redundant.
Expansion therefore needs to be accompanied by well designed, targeted recruitment strategies. This is why
utilisation needs to be considered alongside other issues, including the need to reach an appropriate proportion
of donors from black and ethnic minority groups. 50,000 units has been identified as the optimal size for the
UK’s cord blood inventory: fewer units would result in inferior patient outcomes, but more units would bring only
limited patient gains (Figure 32) (Querol et al. 2009b).
Figure 32 Matching probability relative to the size of a cord inventory (hypothetical)
100
90
80
70
60
% Probability 50
40
30
20
10
0
1
5/6 Match
10
6/6 Match
100
1000
10000 50000 100000 150000
Inventory size
Utilisation
The current cost of a cord blood unit does not reflect the long-term financial viability of a UK inventory. The
utilisation rate of bank, meaning the proportion of its stock selected for HSCT in any given period of time, is a
major determinant of its value and sustainability. By increasing the utilisation rates of its cord blood inventory the
UK could significantly improve its cost effectiveness and lower the real costs per donor/unit dramatically. However,
the utilisation rate of an inventory is also influenced by its size. In theory, in the context of fixed patient demand,
the utilisation rate of a bank should reduce as its size expands.
However, the relationship between the overall utilisation rate of a bank and its size is actually more complex and
balanced out by other considerations. For example, a larger inventory is likely to have a better ‘brand’ in its own
country and internationally, due to the improved HLA range of its stored units and greater associated resources
for marketing and outreach.
Drawing on recent international data (Foeken et a., 2010), Figure 33 illustrates the annual utilisation rates of a
range of cord banks of varying sizes. It is clear from the graph that the relationship between size and utilisation is
ambiguous and complicated by other variables.
52
Part 2: Annexes
Figure 33 1-year utilisation rates relative to size of international cord blood banks
1 Year Utilisation
2.00%
1.80%
1.60%
Utilisation
1.40%
1.20%
1.00%
0.80%
0.60%
0.40%
0.20%
0.00%
0
10000
20000
30000
40000
50000
60000
70000
80000
90000
Bank Size
The cord banks of Mexico, France, Japan, New York and the NMDP together have the highest utilisation rates in
the world (Table 20). However, the inventories service specific populations and vary greatly in size. The high rate
of utilisation in Mexico is due to the small size of the cord blood bank and the relative genetic homogeneity of the
Mexican population. The NMDP, on the other hand, has a large inventory serving an ethnically diverse population:
its utilisation rate is sustained by high levels of domestic demand. France provides a closer comparator for the
UK; its population has similar levels of ethnic diversity. Importantly, with a 1% annual utilisation rate, it achieves
a lifetime utilisation rate of 18.1%, compared to the current rate of 6.5% in the UK. The NMDP, with around 4
times the number of units in its inventory, achieves a similar utilisation rate of 1.1%.
Table 20 Size and utilisation rate of international cord blood banks
Country
Bank Size
1 Yr utilisation
20 Yr utilisation
Mexico
France
Japan
New York
NMDP*
2,300
21,000
73,000
77,000
86,000
1.8%
1.0%
1.2%
0.5%
1.1%
30.5%
18.1%
21.0%
9.7%
20.6%
*National Marrow Donor Program, USA
a 1% utilisation rate is therefore a feasible target for a UK cord inventory of 50,000 units to achieve.
This will inform the cost calculations below.
A Report from the UK Stem Cell Strategic Forum July 2010
53
Ethnic composition
Annex 3 describes in detail the challenges that ethnic minority patients in particular face in locating a donor.
Matching rates for ethnic minority groups on UK and international registries are significantly lower than for
Caucasian patients. Mixed race patients in the UK have a 40.7% probability of locating a suitable donor on the
BBMR, compared to an 88% probability for Caucasian patients.
This imbalance is the result of a number of factors, including:
• Underrepresentation on donor registries – only 5.1% of donors on the BBMR belong to ethnic minority
groups.
• Greater HLA heterogeneity – certain ethnic minority groups have much broader HLA diversity than
Caucasians. The probability that two randomly selected African Americans have matching types is only around
a tenth that of two randomly selected Caucasians (Bergstrom et al, 2008).
• A smaller search pool – as ethnic minorities only make up a fraction of the UK’s population, searching
patients have a smaller donor poll in which to indentify a suitably matched donor.
However, an expanded cord blood inventory offers the possibility of addressing a significant portion of this unmet
need. This is due to a number of reasons, including:
• Targeted recruitment – cord blood lends itself more readily to targeted collection strategies compared to
adult donors. NHS-CBB has 5 collection sites located at hospitals in areas with ethnically diverse populations: as
a result, 39.5% of its stored units were sourced from ethnic minority donors.
• Increased tolerance of HLA mismatch – one of cord’s positive characteristics as a stem cell source is its
ability to tolerate engraftment with a greater degree of mismatch between donor and patient. For patients
with rare haplotypes and a very low probability of locating a 10/10 matched adult donor, cord blood may be
their only option.
Even so, ethnic minority patients still face lower matching rates than Caucasian patients when searching for a
cord unit for transplantation. An inventory of 50,000 units would provide the population as a whole with an 80%
probability of locating a suitably matched unit, but only a 49% probability to ethnic minority patients. To provide
ethnic minority patients with an equivalent 80% chance of finding a match, the inventory would have to expand
to 150,000 units (Querol et al, 2009b). This would results in large numbers of redundant stored units and would
not be economic.
Instead of expanding the inventory beyond 50,000 units, a more effective strategy would be to raise the
proportion of cord blood donations sourced from ethnic minority donors in the inventory. One option would
be to collect cord blood from Black and minority ethnic women exclusively. However, this would mean that
the inventory was unable to supply any Caucasian patients with a match. In terms of utilisation, it is clear that
Caucasian cord blood donations are also in high demand. While around 40% of NHS-CBB’s inventory is sourced
from ethnic minorities, 30% of its issued units are from ethnic minority donors. From these figures it is possible to
deduce the respective matching rates of Caucasian and ethnic minority cord blood donations:
Proportion of units collected originating from ethnic minorities (PC(M)): 0.4
Proportion of units collected originating from non-ethnic minorities (PC(M’)): 0.6
Proportion of units distributed to ethnic minorities (PD(M)): 0.3
Proportion of units distributed to non ethnic minorities (PD(M’)): 0.7
Ratio = PD(M’)/ PC(M’)
PD(M)/ PC(M)
Ratio = 1.56
54
Part 2: Annexes
This means that, due to their higher probability of being matched with a patient, cord blood donations from
Caucasian donors have a higher utilisation rate than cord blood donations from Black and minority ethnic donors.
However, this must be balanced out by the need to extend access to ethnic minority patients and the special role
that a UK cord inventory would play in achieving this. On balance, the range of 30-50% donations from BME
women recommended by Querol et al. (2009b) is a good balance between the need to reduce the unmet need
of BME patients and the considerable demand for and utilisation of cord blood donations from Caucasian donors.
This is the presumed model in the cost benefit analysis that follows.
Profile of Expansion
In order to estimate the costs of an expanded cord blood bank, and the ultimate cost/benefit, it is necessary to
make assumptions about the time profile of expansion. The following assumptions have been made:
• Cord blood would be collected from 13 hospitals organised in 3 geographical clusters over an 8 year period.
• 30% - 50% of the cord blood inventory will be from ethnic minority donors.
• The shelf-life of a cord blood units is 20 years
• At steady state (after 8 years), cord blood will be collected to replace those used or which (in the long run)
have expired.
• Utilisation of the UK cord blood inventory will be 1% per annum (500 units at steady state).
• 33% of collected cord blood units will contain over 90 x 107 TNC.
• 57% of cord blood transplants will involve double units.
The costs of expanding the cord blood inventory to 50,000 units have been based on NHSBT actual expenditure,
treated as variable, stepped fixed and fixed costs, and allocated to supply chain activities using an activity-based
costing model. Table 21 illustrates the strong determining effect that the utilisation rate (0.5%, 1%, 1.5% and
2%) of the inventory would have on the overall cost of every issued cord unit. As much of the costs represent
fixed overheads such as equipment and staff salaries, the difference in collection costs with higher utilisation are
only marginal and represent the extra cord blood donations that must be collected to offset the additional cord
blood donations issued. As the storage costs are largely fixed, these are almost identical in the various models.
For example, at 0.5% utilisation the inventory would incur collection costs of £50.1 million and storage costs of
£6.8 million over the 8 year expansion period, with a total of 1,181 units issued. At 2%, on the other hand, the
total storage costs would still be around £6.8 million and collections costs slightly higher, at £53.5 million – but
with a total of 4,840 units issued, over four times the number issued with 0.5% utilisation. The only significant
difference during the expansion period is the different issue costs, as these are tied directly to the number of cord
blood donations utilised as opposed to the fixed cord blood units of the inventory as a whole. While at 0.5%
utilisation these come to £8.3 million over the 8 year period, with 2% utilisation these come to £26.5 million (this
still represents lower issuing costs per unit). However, given the much larger output of issued units with a higher
utilisation rate, the result is that the real cost of the issued cord including weighting is much lower at 2%. Once
the initial 8 year expansion is complete, the steady state costs of an issued cord unit in an inventory with a 2%
utilisation rate would be only £10k, compared to £25K at 0.5% utilisation (Table 22).
A Report from the UK Stem Cell Strategic Forum July 2010
55
Table 21 Long run costs of a UK cord inventory at 0.5%, 1.0%, 1.5% and 2% annual utilisation
56
Part 2: Annexes
Table 22 Steady state costs of a UK cord inventory at 0.5%, 1.0%, 1.5% and 2% annual utilisation
A Report from the UK Stem Cell Strategic Forum July 2010
57
However, 1% is a more feasible target utilisation rate for the UK’s cord inventory and roughly approximates the
annual unmet demand in the UK that an expanded inventory could be expected to meet (annex 3), particularly
as demand is expected to rise further during the coming decade. Within this range, an expanded cord inventory
could deliver substantial cost savings in the medium term. Despite high costs in the first years as the initial
investment is made, after 3-4 years the cost of a domestic cord unit is cheaper than the cost of a domestic bone
marrow donation. With double cord units, due to the additional costs, domestically sourced cost is cost equivalent
to bone marrow after around 7-8years. However, in both cases the long-term steady state costs are cheaper
than for bone marrow donation or imported cord. To reach 1.5% utilisation, the UK would have to achieve a
significant number of exports in addition to its domestic issues. In this scenario, a domestic cord unit would
become cheaper than a domestic bone marrow donation even earlier. In the long run, the costs of a domestic
cord unit (£16K) would be lower than the cost of a domestic bone marrow donation (£36K) or an imported cord
unit (£45K).
Figure 34 The long run costs of a single cord unit from an expanded inventory of 50,000 units
£80k
Imported Cord
Bone Marrow
1% Utilisation Bank
£60k
1.5% Utilisation Bank
Cost per graft
£40k
£20k
£k
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15
Year
Figure 35 The long run cost of double cord units from an expanded inventory of 50,000 units
£160k
Imported Cord
Bone Marrow
£140k
1% Utilisation Bank
£120k
1.5% Utilisation Bank
£100k
Cost per graft
£80k
£60k
£40k
£20k
£k
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15
Year
58
Part 2: Annexes
Cost-benefit Analysis – an Expanded Cord Blood Inventory
Overview
The cost benefit analysis was carried out by comparing two possible options for expanding the current supply of
cord blood units stored for stem cell transplantation. The options compared are the status quo (expanding the
cord bank to 20,000 units over 4 years) and expanding the bank to 50,000 over 8 years.
The analysis includes costs of donor recruitment, cord collection, storage and transplantation. Benefits are
measure in quality adjusted life years (QALYs). The incremental cost per QALY of expanding to a 50,000 bank was
found to be £27,000.
The results are broadly favourable to a 50,000 cord bank, subject to the assumptions made. However, there
are significant uncertainties surrounding the results. Modelling work suggests that there are possible scenarios
that would result in a unfavourable result for the 50,000 bank. It is recommended that further work be done,
particularly on the benefits side of stem cell transplantation, to make the results more robust.
Options
The analysis consists of a comparison between two proposed options: the status quo and a 50,000 bank option.
The comparison is necessary in order to determine the incremental costs and benefits of moving from the status
quo policy recommendation to a bank of 50,000 donations.
• Option 1 - Status Quo: This option proposes to expand the NHS-CBB inventory to 20,000 banked cord blood
units (the majority containing less than 9 x 108 TNC) over 4 years, and to maintain this level thereafter. There is
existing funding to support this strategy.
• Option 2 - 50,000 Inventory: This option proposes to expand the current inventory to 50,000 over 8 years,
and to maintain it at this level thereafter. It is assumed that once the bank reaches its target capacity, it will
achieve an utilisation of 1% each year. Cord collection will be targeted, aiming to maintain the share of ethnic
minority cord blood units at 30%-50%.
General Modelling Assumptions
• Cord blood units are assumed to have a 20 year shelf life.
• Once the inventory has reached its target capacity, the number of cord blood units will run down to 0 over 30
years through issues for transplants and expiry of donations after 20 years in the bank. This will not happen in
reality; modelling has been done this way simply to ensure the costs align to the benefits.
• In line with HM Treasury Green Book (Annex 6), discount rates of 3.5% for all costs (including NHS cost
savings) and 1.5% for benefits (whether expressed in QALY or monetary values) are applied.
• An opportunity cost uplift of 2.410 is applied to costs as specified in the Department of Health Impact
Assessment Guidance.
• Cord blood units containing less than 90 x 107 TNC are discarded or used for research in line with the
recommendations made elsewhere in the report.
Profile of Expansion
The profile of the expansion was developed in coordination with NHSBT. The profile helps to inform how many
donations were collected and issued in any given year, both under the status quo and the 50,000 inventory
option. It allows costs and benefits to be estimated.
10 The opportunity cost multiplier is commonly found in DH Economic Analyses and Impact Assessments. A QALY is assumed to be valued by society at £60,000.
However, the government can ‘buy’ QALYs through new interventions at around £25,000 on average, reflecting the limited NHS budget. Therefore, to reflect
the ‘opportunity cost’ of spending on stem cell options, i.e. the health gain implicitly foregone elsewhere in the health system,
an uplift of 2.4 (£60,000 divided by £25,000) needs to be applied to all costs and cost savings.
A Report from the UK Stem Cell Strategic Forum July 2010
59
Status Quo
A proportion of the donations in the bank are of low volume, have a low TNC count, and have only been typed
to low resolution. Calculations from NHSBT data show that these low quality donations only achieve a utilisation
of 0.05% while the other donations achieve 0.7%.
A fixed number of high volume donations are added annually the bank over four years, until the overall capacity
of the bank reaches 20,000.
The current number of collection centres will remain constant at five.
The number of cord blood donations used each year is assumed to be equal to the utilisation rates specified
above multiplied by the average number of donations in the bank.
50,000 Inventory
Expanding the UK inventory to 50,000 cord blood units is done with 9 collection centres in year 1, 13 collection
centres from year 2 through to year 6, then 9 collection in centres in years 7 and 8. The centres have been
identified by NHSBT and are chosen for their high ethnic minority populations. Collection rates per centre will
also be increased by having collection take place 24 hours a day, 5 days a week.
The number of cord blood units collected annually remains constant from year 2 through to year 6, when there
are 13 collection centres. The collection rate in years 1, 7 and 8 are roughly the same. This collection profile,
designed by NHSBT, has been chosen to allow a build up of cord blood units at the beginning of the process
and a gradual phasing out of collection towards the end. This is to help mitigate the redundancy costs of closing
down collection centres.
The number of cord blood units stored each year is equal to the existing number of cord blood units in storage,
plus the additional cord blood units collected, minus the cord blood units used and those that expire.
During expansion, utilisation is assumed to be 1% of the average bank size that year.
The number of exports is assumed to be equal to the number of cord blood units needed to be used to bring
utilisation to 1% on top of the cord blood units used domestically. This calculation takes double cord blood unit
usage into account.11
It is estimated that 57% of transplants are double cord blood transplants. This figure is calculated on the basis
that 535 transplants are carried out annually, of which 80 are on children and are all single cord blood unit, and
2/3 of the adult patients receive double cord blood units.
The expansion profiles for status quo and for expansion to 50,000 cord blood units are summarised at Tables 23
and 24.
Table 23 Expansion profile for status quo
Year
0
1
2
3
4
5
6
7
8
Collection
centres
5
5
5
5
5
5
5
5
5
Addition to
2,124 1,961 1,961 1,961 0
bank
Inventorysize 14.3K 16.2K 18.1K 20K
20K
0
0
0
0
Units issued
94
0
62
75
89
95
Total
8,007
19.8K 19.7K 19.6K 19.5K
94
93
92
695
11 This assumption has been made for modelling purposes to ensure that the separate assumptions about unmet need and bank utilisation are internally
consistent. If higher utilisations are achieved, as modelled in the sensitivity analysis, then it is assumed that the proportion of exports will increase.
60
Part 2: Annexes
Table 24 Expansion profile for 50,000 inventory
Year
0
1
2
3
4
5
6
7
8
Collection
centres
Addition to
bank
Inventorysize 7.4K
9
13
13
13
13
13
9
9
Units issued
96
Total
4,336 6,373 6,373 6,373 6,373 6,373 4,438 4,336 44,976
11.6K 17.9K 24.0K 30.1K 36.2K 42.1K 46.1K 50K
148
211
272
333
394
444
483
2,380
Costs and Cost Savings
Cord Blood Inventory Costs
Costs were forecasted from NHSBT actual expenditure (Table 25).
Table 25 Discounted Costs
Status Quo
50,000 Inventory
Collection costs
£8.6m
Storage costs
£9.1m
Issue costs
£9.6m
Collection costs
£49m
Storage costs
£16m
Issue costs
£37m
Transplant Costs
A base estimate of £100,000 per transplant was used in the calculations. This was chosen to be in line with
estimates from the Commissioning Group and with UK cost estimates based on figures collected from van
Agthoven et al. (2002). The total cost is then equal to the number of transplants multiplied by the cost per
transplant.
Alternative Costs
The costs of the alternative treatment to a stem cell transplant are assumed to be £20,000 per patient (based
on $20,702 estimate from Costa et al. (2007)). This is a very approximate assumption, as the cost is likely to be
variable. Alternative treatment may include chemotherapy, palliative care etc. The alternative costs are reported as
a cost saving for each transplant, with the overall saving equal to the number of transplants multiplied by costs.
Export Cost Recovery
Some costs will be recovered through exporting cord blood. The current price of £19,050 charged by NHSBT per
exported unit (Sussex et al. 2010) is assumed to remain constant over the 30 years of the analysis, with alternative
options explored in the sensitivity analysis.
R&D Cost Recovery
• £200 net income assumed to be received per cord blood unit (after taking the cost of processing into account).
• Demand from the research community is forecast to be 500 in year 1, 800 in year 2 and 1,000 in year 3.
• There will be sufficient supply to meet demand under either status quo or the 50,000 cord option during the
expansion phase, hence R&D cost recovery will have little effect on the incremental costs of expansion.
A Report from the UK Stem Cell Strategic Forum July 2010
61
Health Gains
Population Life Expectancy and QALY Expectancy
Future life expectancy for different age groups was constructed, based on historic ONS survival data. Each age
group was assigned average QALY values which were discounted at 1.5% per annum (the standard DH rate).
Calculation of mortality rates
Survival data at 5, 10 and 15 year were taken from a selection of published papers, with and without transplant.
Annual mortality rates were then calculated across the period assuming that:
• For transplant recipients the mortality rate doubled in year 1 and remained constant thereafter. For nontransplant recipients the mortality rate remained constant across the period.
• Relative mortality rates in years 5 to 20 following transplantation were taken from Bhatia et al. (2007). The
rates were: 8.3 times the population mortality in years 6-10, 3.7 times in years 11-15, 2.9 times in years 16-20.
Relative mortality was assumed to be double the ONS population mortality rate thereafter.
Calculation of QALY gains
Adjusted mortality rates are used to calculate life expectancy with and without a transplant. QALY values per
year are downgraded by a factor 0.8, to reflect co-morbidities and continuing lower health-related quality of life.
Future QALY expectancy with and without transplant is netted to give the QALY gain.
QALY assumptions
A QALY gain of 2.96 per transplant was picked, which corresponds to the gain for a 30 year old with acute
lymphoblastic leukaemia or acute myeloid leukaemia using Costa et al. (2007) figures. This representative figure
was chosen to reflect the average age patients receiving cord blood transplantations. Other QALY gain values are
tested in the sensitivity analysis.
The overall QALY gain was calculated by taking the product of 2.96 and the number of domestic transplants. For
the net present value calculation (NPV) the QALY gain was converted to a monetary equivalent assuming a value
of £60,000 per QALY
Complete Assumptions
Table 26 summarises the assumptions used to estimate QALYs gained from HSCT
62
Part 2: Annexes
Table 26 Summary table of assumptions and data sources
Data
Figure
Source
Unmet need
440
Expert judgment (Annex 3)
Unmet need met by 50,000 bank
370
Expert judgment (Annex 3)
Option 1 utilisation – low quality CB
0.05%
Calculated
Option 1 utilisation – high quality CB
0.7%
Calculated
Option 2 utilisation
1%
Assumption
Imported CB per annum
99
OHE report
Imported CB transplants
73
OHE report
Import price
£29,879
OHE report
Export price
£19,050
OHE report
Healthcare costs without transplant
£20,000
Costa et al. (2007)
Healthcare costs with transplant
£100,000
van Agthoven et al. (2002)
Transplant QALY gain
2.96
Costa et al. (2007)
CB units per transplant
1.57
Expert judgment
QALY value
£60,000
DH Impact Assessment Guidance
Opportunity cost uplift
2.4
DH Impact Assessment Guidance
Storage costs
NHSBT
Cost per QALY Results
Table 27 summarises the discounted total costs for each option and for the difference between the two. The cost
per QALY of £27,000 is within the £30,000 threshold typically used to evaluate DH spending decisions. The case
for a 50,000 bank appears broadly reasonable.
Table 27 Costs per QALY
Status Quo
50,000 Bank
Incremental
Discounted total costs
£250m
Discounted QALY
£7.8k
Discounted total costs
£547m
Discounted QALY
£19k
Discounted total costs
£297m
Discounted QALY
£11k
Cost per QALY
£27k
A Report from the UK Stem Cell Strategic Forum July 2010
63
Univariate Sensitivity Analysis
As this analysis is based on a number of assumptions based on judgement, there is a significant amount of
uncertainty surrounding the results. This section presents the results of a sensitivity analysis on the key parameters
in the model, and serves to verify that a result is not driven by an overarching assumption about any single
parameter. In this way, a sensitivity analysis can be considered to improve the robustness of the potential
conclusions drawn from the cost benefit analysis.
The analysis works by varying individual parameters one by one while holding the remaining parameters constant.
This makes it possible to observe the impact individual parameters have on the final results and thus asses the
degree of uncertainty surrounding the results.
Table 28 presents the results of the sensitivity analysis. This demonstrates that there is significant weight attached
to uncertainty in health benefits. Altering the QALY gain associated with a transplant by a small amount results
in a significant change in both the cost per QALY and the net benefit. This is a key uncertainty as the QALY gain
following a transplant varies across age groups.
Alternative costs, transplant costs and utilisation have a large influence on the net benefit. Hence, there is
uncertainty about the overall cost to the NHS and not just around the collection of stem cells.
A higher level of utilisation would strengthen the case for a cord bank expansion. However, a higher level
of utilisation than 1% is not supported by international comparisons or by the current level of unmet need.
Achieving a higher level of unmet need would thus rely on a high level of exports.
Single cord transplants are more cost effective than double transplants. However, for most adults, the
effectiveness of a transplant is significantly increased with a double cord, resulting in a higher QALY gain.
Changing the price of exports does not make a significant impact, unless there are a large number of exports.
Variations in R&D sales prices also have an insignificant impact on cost per QALY and net benefit.
64
Part 2: Annexes
Table 28 Sensitivity analysis
Parameter
Original
Sensitivity
Cost per
Value
Value
QALY
Base case
Alternative costs
Transplant costs
QALY gain
Utilisation (future)
£20,000
£100,000
2.96
1%
NPV*
£27,000
-£52.7m
£40,000
£21,691
£87.3m
£10,000
£29,655
-£122.8m
£80,000
£21,691
£87.3m
£120,000
£32,309
-£192.8m
2
£39,960
-£266.6m
3
£26,640
-£43.8m
4
£19,980
£178.9m
5
£15,984
£401.7m
0.50%
£32,765
-£94.3m
1.50%
£23,581
£38.3m
2.00%
£20,227
£127.5m
200
£24,303
£8.2m
500
£27,228
-£65.7m
£3,000
£26,309
-£34.5m
£6,000
£28,051
-£80.5m
1.00
£24,133
£22.9m
2.00
£28,883
-£89.7m
£10,000
£27,443
-£64.4m
£13,500
£27,272
-£59.9m
£25,000
£26,709
-£45.1m
£0
£27,077
-£54.8m
£100
£27,038
-£53.8m
Met unmet demand in
long run
359
Issue cost
(variable+step fixed
only)
Double cord ratio
Export price
R+D sales price
£4,190
1.567
£19,050
£200
*Net Present Value
A Report from the UK Stem Cell Strategic Forum July 2010
65
Monte Carlo Analysis
A Monte Carlo analysis allows the overall uncertainty of the results to be assessed. The simulation is run by
allowing the parameters of the model to be drawn from uniform distributions between pre specified values.
The parameters are then picked at random from their distributions and plugged into the model. The process is
repeated 10,000 times, allowing a distribution of results to be constructed.
Table 29 lists the parameters of the model, as well as their lower and upper bounds between which their values
are distributed uniformly.
Table 29 Parameter ranges
Parameter
Base Case
Lower Bound
Upper Bound
Alternative costs
-£20,000
-£10,000
-£30,000
Transplant costs
£100,000
£75,000
£125,000
QALY gain
2.96
1.96
3.96
Unmet need at steady state
358.5
208.5
508.5
Future utilisation
1.00%
0.50%
1.50%
Proportion with acceptable TNC range
0.328
0.228
0.428
Typing & testing
£106.88
£81.88
£131.88
Issue
£4,189.74
£3,189.74
£5,189.74
Export revenue
-£19,050
-£14,050
-£24,050
Double cord blood transplants
1.567
1.267
1.867
Figure 36 shows the frequency distribution of the incremental cost per QALYs resulting from the 10,000
simulations. The base case cost per QALY (£27,000) and the 10th and 90th percentiles are marked on the
distribution and shown in Table 30.
Figure 36 Cost per QALY distribution
600
Base Case
500
Frequency
400
10th Percentile
300
90th Percentile
200
100
0
£0
£10,000
£20,000
£30,000
£40,000
Cost per QALY
66
Part 2: Annexes
£50,000
£60,000
Figure 37 shows the frequency distribution of the net present value of incremental benefits.
Figure 37 Frequency distribution of net present value
Frequency Distribution of NPV
1400
1200
Frequency
1000
800
600
400
200
0
-£700m -£600m -£500m -£400m -£300m -£200m -£100m
£0m
£100m
£200m
£300m
£400m
£500m
£600m
£700m
£800m
£900m
NPV
Table 30 Monte Carlo results
Variable
Mean
Median
10th Percentile
90th Percentile
Cost per QALY
£26,728
£27,078
£18,698
£39,301
NPV
-£39.1m
-£43.7m
£167.3m
-£239.4m
This analysis highlights the uncertainty in the model. The range of possible costs per QALY is wide and although
the base case estimate falls under the £30,000 threshold commonly used by the Department of Health, there is a
significant probability that the cost per QALY could exceed the threshold.
Conclusions
The results are broadly favourable to a move to a cord blood inventory of 50,000 units, based on the base case
assumptions. The base case estimate of cost per QALY of £27K is within the typical threshold of £20,000 £30,000. However, both the sensitivity analysis and the Monte Carlo simulation highlight a significant amount of
uncertainty surrounding the results. Whether the expansion to 50,000 unit capacity is found to be cost beneficial
or not depends on the values of the parameters inputted into the model. In particular, the key uncertainties are
around the costs and benefits of stem cell transplantation, rather than the cost of collecting and banking cord
blood to expand the bank. Further research, particularly on patient outcomes, would be advisable.
A Report from the UK Stem Cell Strategic Forum July 2010
67
Annex 9
The Commissioning of Unrelated Donor Stem Cell Transplantation in the UK
Summary
Commissioning practice across the UK is currently fragmented, with no nationally agreed set of protocols
for recipients of allogeneic stem cell transplantation. A standardised service framework should therefore be
developed to govern all contractual agreements between Specialist Commissioning Groups (SCGs) and providers.
This should include clearly delineated and baseline costing frameworks. In line with the 2010/11 NHS Operating
Framework, it should place a strong emphasis on service equality, accountability, information transparency and
outcome data.
There are currently 34 transplant centres performing allografts from sibling or unrelated donors in the UK, but
transplant activity is distributed very unevenly among them. In 2009, 54% of all allogeneic transplants were
undertaken by ten centres, compared to only 10% by the ten least active centres. Thirty UK centres currently
perform unrelated donor or cord blood transplants and a similar marked disparity in transplant activity is evident.
Given the increased complexity and attendant morbidity and mortality of alternative donor transplants SCGs should
undertake a designation process to identify Regional Centres of Excellence in Alternative Donor Transplantation
serving a population in the region of 4-5 million. Cord blood transplants which are associated with a particularly
high transplant related mortality should be exclusively commissioned from such Centres of Excellence. Rare
haematological diseases, particularly non-malignant conditions, should also be treated at centres with specialist
knowledge of them. Furthermore, to resolve the current lack of uniform and reliable data, designated centres
should be obliged to monitor and report all patient outcomes at the same time as being provided with the required
data management personnel. Commissioners should work with clinicians to develop registration studies and
clinical trials in alternative donor stem cell transplantation in order to improve patient outcome. These measures
would give Commissioners a clear picture of individual performance and clinical trends and facilitate informed and
effective commissioning decisions with the aim of delivering the best possible patient outcome.
HSCT Performance in the UK: Challenges and Opportunities
A recent analysis of transplant outcomes found a correlation between the number of HSCT performed in a
Country and its position on the Human Development Index (HDI). The UK was ranked at the top of the second
highest quintile of Countries. As transplant performance is influenced to a significant degree by a country’s stage
of development and its health expenditure, this suggests the UK is still some distance from achieving its full
potential as a leader in world class commissioning for HSCT.
The Carter Review highlighted a number of key areas where pathology services in general should be strengthened
(DH, 2006). Many of these are directly applicable to the processes surrounding HSCT in the UK. The review
identified a number of challenges and opportunities, including:
• Service fragmentation and complex cost structures - care provision and service costs were often spread
across multiple authorities, resulting in complex pricing structures that were difficult to gauge.
• Local flexibility, within a UK specification - while allowing the NHS to maintain its strengths as a patientand commissioner-led service, there should also be a clear UK specification to guide these services across the
country.
• The lack of a solid and standardised evidence base - common templates should be developed to facilitate
the collection of uniform data sets on service costs and activity levels. Commissioners should ensure these
mechanisms are in place.
• The development of clear contractual agreements for providers – commissioners should incorporate
service specifications in their contracts with providers, including performance criteria and defined levels of
reimbursement.
These recommendations are also relevant for commissioners reconfiguring transplant procedures at an SCG
and UK level. The rest of this section discusses the current limitations affecting HSCT commissioning and some
emerging solutions.
68
Part 2: Annexes
Standardised Contracts
The patient pathway for an HSCT recipient spans months or even years of pre- and post-transplant treatment.
Typically, this involves input from multiple bodies and organisations, including hospitals, stem cell providers,
SCGs, and Primary Care Trusts (PCTs). However, a recent survey of SCG service frameworks conducted for this
Strategic Review found considerable divergence between them in terms of cost allocations and responsibilities.
It was apparent from the responses that governance is frequently fragmented between different groups, with
no common operational or financial remit. Table 31 illustrates the differences in the funding mechanisms at
three anonymised SCGs. While SCG A manages the whole patient journey from referral to discharge, B and C
to varying degrees cover only part of the care pathway, leaving local PCTs to oversee the remaining stages of the
patient’s treatment.
Table 31 Commissioning models at different SCGs
Provider
Pre-transplant
A
Transplant
Post-transplant
SCG/consortium funded
B
PCT funded
C
PCT funded
SCG/consortium funded
PCT funded
SCG/consortium funded
The London Pan Thames Consortium has developed and recently introduced a standardised approach to
commissioning the service with all its care providers that defines the specialised commissioning responsibility across
the patient’s treatment pathway. In this model, drawing on the work of a multi-disciplinary team, the SCG has
procurement oversight of the whole patient pathway, which also allows for shared care arrangements into defined
treatment phases: from the initial pre-transplant patient work-up to the subsequent outpatient follow-up up to
100 days later (Table 32). The funding to undertake each of these phases is allocated according to a set percentage
of the overall fixed cost of HSCT (including treatment before and after transplant) for the patient. As a result,
costs and funding are uniform and transparent, defined according to the established National Specialised Services
Definition Set, giving both commissioners and clinicians a clear picture of their responsibilities and also what they
may reasonably expect. This is likely to remedy the confusion of conflicting tariff structures and service agreements.
Table 32 London consortium costing template, by phase of HSCT
Phase 1
Decision to transplant, patient assessment, investigations, donor
matching /selection / testing / HLA typing.
Phase 2
Patient and donor work up.
Phase 3
Stem cell collection, stem cell manipulation and may involve provision of
GCSF/ patient work up, etc.
Phase 4
Transplant admission, conditioning regimen and stem cell infusion.
Management of pancytopenic phase and graft vs. host disease.
Phase 5
Occasional requirement for repeat stem cell Infusion with / without
chemo therapy if graft failure occurs.
Phase 6
Disc harge to 100 day follow up, including management of acute graft
versus host disease, infections and other complications.
Phase 7
Management of complex issues, 100 days onwards: graft vs. host
disease, secondary malignancy, opportunistic infections, excluding
donor lymphocyte infusions. Not included in costing calculations.
Phase 8
Donor lymphocyte infusions not included in costing calculation.
As the format has been framed around established national definitions, it could be adapted by other SCGs to
implement within their own jurisdiction.
A Report from the UK Stem Cell Strategic Forum July 2010
69
SCG costing templates also need to accommodate uncertain or fluctuating costs, particularly with stem cell
procurement. Within the UK, domestically sourced adult donations incur roughly the same costs for providers
and can therefore be reasonably streamlined into a single UK-wide tariff. The same is not true for internationally
sourced donations, where the charges vary considerably depending on the registry. In 2009, import costs for
adult stem cells varied from £10K to 18K depending on source. For cord blood stem cells the acquisition costs
were more variable and in some circumstances were as much as £75K for a double cord acquisition. Cord blood
acquisition should therefore be considered as an option for ring fenced funding until it is sufficiently established
to conform to similar funding frameworks as per other acquisitions. Critically, these costs must be guaranteed
with central funding and the decision to undertake stem cell transplantation must be determined by clinical rather
than any economic considerations.
Transplant Centre Output
Thirty four transplant centres performed allogeneic stem cell transplants in 2009. However, a large portion of this
activity was concentrated in a small number of transplant centres: 27% of allografts were performed by the four
most active centres. The ten most active and ten least active centres were together responsible for 54 and 10%
of allogeneic transplant activity respectively (Figure 38). There is increasing evidence that centres performing a
higher number of complex transplants achieve superior outcomes when compared to centres with low levels of
HSCT activity (Cohen et al. 2010; Klingebiel et al. 2010; Frassoni et al. 2000; Katsahian et al. 2010) although it
should be noted that the evidence supporting a correlation between centre activity and outcomes is difficult to
interpret, largely because of statistical challenges in the interpretation of very small datasets (e.g. from transplant
units with low levels of activity). Nevertheless, recent data made available to the Forum by the EBMT further
supports the previously published evidence of a centre effect (vide supra). In a study of 1413 patients with acute
myeloid leukaemia, those transplanted at centres performing fewer than 15 allografts per annum had significantly
reduced leukaemia-free survival, increased relapse and increased post-transplant mortality (V. Rocha, personal
communication to the review). Recent data identifies this effect to be particularly marked in recipients of cord
blood transplants (Cohen et al. 2010).
Figure 38 Allograft activity by UK transplant centre, 2009
120
100
80
Allografts 60
40
20
0
1
Centre
34
Cord blood is still a relatively small contributor to HSCT activity. In 2009, 14% of unrelated donor transplants were
performed with cord blood (WMDA, 2009). Thus, activity is relatively low at the 20 transplant centres undertaking
CBT: only 8 performed 5 or more transplants. This modest output was significantly larger than the level of the
less active centres, where only one or two CBTs were carried out over the entire year (Figure 37). Accumulating
evidence demonstrates that CBT is associated with a complex constellation of complications resulting in a
particularly high risk of transplant related death and late complications (Eapen et al. 2010). Consequently,
the current pattern of distribution of CBT activity is very likely to adversely impact on patient outcomes unless
methods by which specialist clinical expertise in CBT can be developed.
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Figure 39 Cord transplant activity by centre, 2009
12
10
8
CBTs 6
4
2
0
A B C D E
F
G H
I
J
K L M N O P Q R
S
T
Transplant centre
Designation of ‘Centres of Excellence’
HSCT is a highly complex procedure requiring considerable experience and expertise. This is particularly the case in
recipients of unrelated donor or cord blood stem cells where the risk of dying of transplant related causes in the
first year post-transplant is in the region of 30%. Coupled with the substantial long term morbidities associated
with unrelated donor transplantation there is a compelling case for such expensive and complex procedures to
be performed only by a skilled team of clinicians, nurses and ancillary medical staff. These arguments increasingly
apply if a sustainable service is to be delivered in the context of the European Working Time Directive given the
importance of delivering high cost treatments in as cost-effective a manner as possible. Given the relatively small
number of unrelated transplants performed within the UK annually the only reliable mechanism to ensure quality
and optimise patient outcome is through Commissioner led designation of Regional Centres of Excellence in
Alternative Donor Transplantation. This is particularly true in cord blood transplantation where establishment of
a Regional Centre serving a population of no less than 4 million is essential in order to prevent one of the most
complex procedures commissioned by the NHS, with the capacity to deliver curative therapy in a significant
number of patients, being delivered by teams with minimal experience.
It is apparent that a well managed strategy of centralisation could achieve substantial benefits, including:
• Better patient outcomes - Centres performing a higher number of transplants achieve on average superior
outcomes when compared to centres with low levels of HSCT activity (Cohen et al. 2010; Klingebiel et al.
2010; Frassoni et al. 2000; Katsahian et al. 2010). More generally, centralisation of specialised services has
occurred across a range of fields in recent years with the guiding aim of improving the quality of patient
care by concentrating resources and expertise. Examples include cardiac care, trauma management, stroke
treatment and other cancer divisions. SCGs should therefore exploit the opportunity to achieve world class
commissioning practice through the development of designated Centres of Excellence for allogeneic stem cell
transplantation.
• Improved cost effectiveness - a centralised model of service delivery is likely to prove more financially
sustainable. As the operational costs of specialist staff and equipment are considerable, a smaller number of
high activity Centres of Excellence should be more cost effective. In particular, it would help reduce service
replication and overlap in areas such as apheresis, quality management and stem cell laboratories. This could
result in substantial savings.
A Report from the UK Stem Cell Strategic Forum July 2010
71
An additional important consideration in the commissioning of transplant services is the treatment of rarer
diseases. While allografts treat a wide range of conditions, the large majority of these fall into a few common
diseases categories, such as acute leukaemia, chronic leukaemia, myelodysplastic syndrome, myeloproliferative
syndromes, and lymphoma. However, a number of other HSCT-treatable conditions, particularly in paediatric
patients, occur only infrequently: for instance, in 2009 there were only 15 cases of inherited metabolic disorders
and 4 cases of autoimmune disease (Figure 40). Spread across multiple transplant centres, this means that certain
conditions are being treated by individual centres once a year or less, with potentially sub-optimal consequences
for patient. As part of an improved commissioning process, SCGs should consider, in partnership, the designation
of particular centres to treat rare diseases. This may require strategic collaboration between multiple SCGs, with
disease-specific centres operating within a regional remit. It should be noted that within paediatric diseases there
is already currently a strong process of self-regulation. Given the rarity of some of the paediatric diseases under
consideration such as immunodeficiencies and inborn errors of metabolism flexibility should be exercised in the
application of these recommendations although JACIE accreditation remains an absolute pre-requisite.
Figure 40 Unrelated donor transplantation activity by condition, 2009
600
500
400
Allografts 300
200
100
0
Cord Transplant Centre Designation
For cord blood transplantation, a minimum threshold of 5 transplants annually would allow centres to develop
expertise and the required infrastructure. As UK cord blood transplant activity for adult patients increases it is
recommended that the minimum threshold should be increased to 10 cord blood transplants annually for adult
transplant centres. A recent analysis of cord blood transplant outcomes from three registries found that transplant
centre experience was significantly related to survival outcomes at 100 days and 1 year (Cohen et al. 2010).
As well as conforming to JACIE standards and UK protocols, transplant centres should be required to secure
commissioner backing before extending their activities to cord blood transplantation. GP commissioner backing is
now a stipulated component of the 2010/11 NHS Operating Framework.
Outside London, SCGs should consider focusing cord blood transplantation into a single specialist unit serving a
population base of 4 million or more. The current situation within the UK of competing transplant units within
a single region ensuring neither centre can achieve the necessary expertise cannot be supported on the grounds
of either clinical governance or responsible use of limited health service resources. These Regional Centres
of Excellence will naturally become the focus for unrelated donor as well as cord blood transplantation and
Commissioners may wish to consider this in the Designation of Centres of Excellence. In some parts of the country
where CBTs are rare, generally areas with low ethnic minority representation, SCGs should consider whether
patient referral outside their own network to another SCG might be a more appropriate strategy. Only 5 of the 8
UK SCGs and 1 devolved administration that undertook cord blood transplantation in 2009 performed more than
5 procedures (Figure 41).
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Part 2: Annexes
Figure 41 Cord transplant activity by SCG
35
30
25
C
B 20
T 15
s
10
5
0
A
B
C
D
E
F
G
H
I
SCG/Dev. Admin.
There is a significant risk of insufficient expertise in cord blood transplantation in adults; of the 8 transplant
centres performing 5 or more CBTs during 2009, 3 transplanted paediatric patients only. At present, only one
adult transplant centre in the UK has performed more than 20 CBTs. Individually or in partnership, SCGs should
respond to this in their designation strategy. Taken together these data support the recommendation in this report
that the commissioning process for cord blood transplantation must be reformed to ensure the development of
Regional Centres of Excellence.
Geography, Patient Access and Networks of ‘Shared Care’
A designation process would necessarily involve a reduction in the number of centres undertaking unrelated
donor stem cell transplants. However, determining a precise activity threshold for the designation process may be
difficult in some more scarcely populated areas of the country and in this setting may incorporate considerations
in addition to those set out for minimum levels of activity. In identifying Centres of Excellence, SCGs should take
account of the geographic reach of their services, the population base they serve and the demand for locally
available services, where feasible. Figures 42 and 43 (BSBMT, 2010) illustrate the uneven distribution of HSCT
activity across the UK. Transplant centres of a certain size and performance level that might not qualify as a Centre
of Excellence in London or another major metropolitan area might be seen to qualify in other less populous areas
of the UK.
Figure 42 Geographic concentration of adult transplant activity in the UK, 2009
A Report from the UK Stem Cell Strategic Forum July 2010
73
Figure 43 Geographic concentration of paediatric transplant activity in the UK, 2009
Increasing Understanding Among Commissioners
Education is central to bridging the knowledge gap between commissioners and clinicians. Information sharing
and readily accessible information tools will result in better informed and more collaborative decision making.
Commissioners should understand what they are approving and what standards they should reasonably expect.
Knowledge outreach between clinicians and commissioners would benefit both parties and strengthen trust and
understanding between them. This could be achieved through a variety of approaches, including:
• Meetings – commissioners should be invited to major clinical meetings, such as the BSBMT, EBMT and JACIE
meetings. The BSBMT already hosts an annual scientific and education day which would allow clinicians to
update commissioners with presentations on the latest developments in the field.
• Data gathering – BSBMT is now gathering standardised indications data from transplant centres and collating
it in an annual report. This will give commissioners a clearer picture of current trends and help improve strategy
development.
• Collaboration – transparent governance and information flows between different bodies would also
strengthen partnerships. For instance, the local network annual report could be shared with each of the
regional commissioners to facilitate a more collaborative relationship.
• Literature and multimedia – leaflets, books and videos designed for non-clinicians may improve
understanding among commissioners. However, funding to support this would be required. Charities and
research organisations such as Macmillan, Cancer UK and Leukaemia & Lymphoma Research already have a
wealth of published resources that could be adapted for use as an education tool among commissioners.
• Established communication networks – local commissioners should have regular exposure to national and
international best practice through a well structured network linking local SCGs with the BSBMT and larger
organisations such as the EBMT.
Embedding Best Practice in The UK
UK Regulation
A significant proportion of UK transplant centres are already accredited by JACIE.12 JACIE accreditation should
be a requirement of the SCG designation process and providers who have not been accredited should be
advised of a timescale when this should be completed. This will require coordinated access to related clinical
12 The Joint Accreditation Committee-ISCT (Europe) & EBMT is a non-profit body established in 1998 for the purposes of assessment and accreditation in the field
of haemopoietic stem cell transplantation. JACIE’s primary aim is to promote high quality patient care and laboratory performance in haematopoietic stem cell
collection, processing and transplantation centres through an internationally recognised system of accreditation.
The Committee was founded by the European Group for Blood and Marrow Transplantation and the International Society for Cellular Therapy, the two leading
scientific organisations involved with transplantation in Europe. JACIE, in collaboration with the Foundation for the Accreditation of Cellular Therapy (FACT),
has established standards for the provision of quality medical and laboratory practice in HSC transplantation; conducts inspections, and accredits programmes.
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Part 2: Annexes
divisions, including cardiac, renal, respiratory and intensive care facilities. In addition, many centres are accredited
or licensed by other bodies, including the Human Tissue Authority, the Medicines and Healthcare products
Regulatory Agency and Clinical Pathology Accreditation.
The UK should take the opportunity to further expand its protocols as a positive step towards maintaining its
strength as a leader in HSCT provision. Given the complexity of HSCT, closer alignment with other specialisms at
Centres of Excellence would be beneficial. This could extend to storage facilities, HLA typing and quality assured
on-site laboratories, in line with recommendations in the 2006 Carter Review.
Clinical Trials and Data Collection
Commissioning should be directed by the latest guidance and benchmarking from organisations such as
BSBMT, the EBMT, the National Cancer Research Network (NCRN) and the British Committee for Standards in
Haematology (BCSH). Commissioning strategies should reflect recent findings from clinical trials such as those
organised by the BSBMT Clinical Trials Committee (CTC) to ensure all patients are have access to HSCT where
clinically appropriate.
The use of nationally agreed transplant protocols and regular data collection is essential for commissioners to
develop a clear picture of current transplant outcomes and the performance of individual transplant centres.
Commissioners should therefore work with clinicians to develop registration studies and clinical trials in alternative
donor stem cell transplantation in order to improve patient outcome. To do this effectively, transplant centres
need sufficient resources to support the additional costs. In the London SCG, this is now a mandatory part of the
contractual agreement with service providers. With commissioning funds, the BSBMT is now producing a 5-year
rolling outcome audit on all adult transplant patients. Data collection is essential for commissioners to undertake
informed horizon planning for service development and is a central component of the “information transparency
agenda” in the 2010/11 NHS Operating Framework. It is therefore recommended that the infrastructure and
personnel be provided within Regional Centres of Excellence to accurately measure patient outcome. At the same
time it is recommended that a clinical trial network through which registration studies and clinical trials in alternative
donor stem cell transplantation can be developed and run is funded as part of the Commissioning process.
Designed Care Networks
SCG commissioners should ensure that patients within their jurisdiction are readily referred by local networks
to designated Regional Centres of Excellence to ensure equity of access to the full range of UK services. At
the same time, in partnership with clinicians, SCGs should develop well structured systems of shared care to
allow secondary treatments to be provided locally, so enhancing patient access and easing the burden on core
transplant centres. Commissioners should draft this into guidance tools, clearly outlining the distinct roles and
responsibilities of designated Centres of Excellence and secondary care facilities.
Centre designation should also be guided by a national steer, with UK transplant centres monitored and managed
by a regional or national oversight body. There should also be a loose coalition of networked SCGs to facilitate
communication and information flows between them.
Standardisation and National Management
It is important that data collection, contractual agreements and transplant centre activity is framed within a
national specification. In particular, SCGs should move towards a single uniform template to guide procedures
between different bodies and divisions. This does not preclude regional and local decision-making, but ensures a
common framework for service provision and patient care.
A Report from the UK Stem Cell Strategic Forum July 2010
75
Annex 10
The Value of Research and Development In Unrelated Donor Stem Cell
Transplantation and Regenerative Medicine
Summary
A framework to optimise the use of stem cell therapies through research and development should be an integral
part of a nationally organized unrelated donor blood stem cell program. Such a program is also required to
maintain the UK’s leadership position in stem cell therapy and biology for the benefit of patients and the economy.
Unrelated Blood Stem Cell Transplantation
Human stem cells can be derived from three major sources: embryos, umbilical cord blood and adult tissues. Adult
blood stem cells isolated from bone marrow of siblings of patients have been successfully used in transplantation
to save lives of patients with blood cancers for over 40 years. More recently, umbilical cord blood stem cells and
stem cells from unrelated donors have been successfully transplanted to treat patients without a sibling donor.
In addition, the UK has also led efforts to exploit the enormous health care potential of novel stem cell-based
therapies for serious diseases where limited, or no, treatment options are currently available.
The number of unrelated donor stem cell transplants has increased steadily in the UK over recent years (Annex 1).
This increasing activity is mirrored in Europe. Although unrelated donor HSCT is a proven life-saving therapy, it is
expensive and associated with considerable morbidity: 40-60% of patients still die after transplant. The optimal
indications for HSCT and methods to deliver the transplant still need to be refined. This is not surprising as it is a
complex treatment that is still being developed. Thus, there is a strong rationale for an integrated Research and
Development program to reduce the cost of, and improve patient outcomes from, unrelated donor HSCT.
Cord Blood Stem Cells for Discovery Research
Enormous opportunities exist for discovery research to develop innovative future therapies for blood diseases and
more broadly, for a much larger population, that suffers from common degenerative diseases such as Alzheimer’s
and Parkinson’s diseases, paralysis due to spinal cord injury, heart failure, liver disease, and Type I diabetes (Table 33).
A human is able to regenerate some tissues. For example, blood and skin are continuously restored, and bone,
muscle, liver, and blood vessels have a limited self-renewal capacity. However, other tissues (e.g. joints or the
brain) are not easily repaired after trauma or disease. Although many drugs alleviate symptoms, most fail to
restore normal function to damaged tissue. Replacing a damaged organ with a donor organ is not always
possible, is expensive and often associated with morbidity and mortality. Stem cell-based therapies offer the
potential for cure. Some estimates, suggest a $30 billion market for cell-based therapies, the majority of which
could be based on blood stem cells.
Table 33 Indications that may benefit from blood/bone marrow derived stem cell-based therapies
Indication
Myocardial infarction
Congestive heart failure
Stroke
Type I Diabetes
Osteoarthritis
Alzheimer’s disease
Parkinson’s disease
Spinal cord injuries
Hematopoietic stem cell transplants
Source: K Bingham, SV Life Sciences.
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Part 2: Annexes
U.S. Patient Population
7.2 million
5 million
5.5 million
2 million
43 million
4.5 million
1 million
0.25 million
18 thousand
Cord blood stem cells offer an easily-accessible stem cell source to study basic and translational stem cell
biology to provide novel drug and/or cell-based therapy to restore normal organ function either by stimulating
endogenous stem cells or providing exogenous stem cells. Stem cell research has attracted academic research
funding (both Government and charitable sectors). The UK is a world leader in stem cell science with
internationally competitive University based programs in Oxford, Cambridge, London and Newcastle. However,
the science is still immature and not helped by poor access to high quality stem cells for research. There is
interest from commercial biopharma and biotech but this is more prominent in the US. Few UK-based stem cell
based companies exist and the structure to interface with UK-based scientists needs development. Despite this,
clear opportunities for commercial exploitation of cord blood stem cells exist and this Review provides a timely
opportunity to facilitate UK-based discovery stem cell research and integrate it with private commercial ventures
and clinical Centres of Excellence that can conduct clinical trials of stem cell therapies.
Examples of Key Research and Development Opportunities
Clinical Studies To Optimize Cord Blood Stem Cell Transplantation (Figure 44)
1. Establishing a comprehensive national registry to collect clinical outcome and health economic data on
unrelated donor blood transplants. This is critical to ensure uniform best practice and collect cost-benefit data
on unrelated donor HSCT.
2. Establishing national clinical trials of unrelated donor HSCT to test the indications and methods on how to
best to deliver expensive and complex transplants. This would also allow for uniform data sets that facilitate
evaluation of best practice.
Figure 44 Expanding clinical transplant capability
Expanding clinical transplant research capability
Clinical Research Unit
Registration of all transplants
Web-based data collection: procedure
outcome, quality of life, health economic
data.
Monitor and set practice – nationally
agreed protocols – uniform data sets.
Implementation of best practice
Clinical units
Clinical trial portfolio
Phase I/II; Phase III – linked to national
disease trial groups
Biological / translational studies –
characterise immune effector response,
haemopoietic stem and progenitor
content
Sample collection from cohorts
Scientific labs with
appropriate technology and
interests in translational
questions
Translational and Clinical Research (Figure 45)
1. The outcome of transplantation depends on stem cells and the cells they generate (progenitor cells) being
able to reconstitute normal blood cells. Thus, it is important to prospectively characterize the number
and function of stem and progenitor cells in donor stem collections that are stored and those that are
transplanted.
2. The outcome of HSCT also depends on transplanted stem and progenitor cells generating immune cells
capable of recognizing and destroying patient’s cancer cells. Thus, it is important to prospectively characterize
the number and function of immune effector cells in stem blood collections that are stored and those that are
transplanted.
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77
3. Clinical trials need to have attached biological studies to explore of the use of cord blood stem cells in
regenerative medicine. An example would be to explore stem cell therapy for degenerative joint disease,
which affects circa 10% of the UK population. In early stages of degenerative knee joint disease cartilage
at articular surfaces is defective. One operation currently performed routinely in the NHS is to abrade the
cartilage to release bone marrow cells, which transform to fibrocartilage to provide a useful repair. However,
this crude repair only lasts for only 3-6 years and is only effective in a proportion of patients. An important
question in the field would be to define stem cell populations that would be more effective at cartilage
formation without forming the fibrous tissue that compromises repair.
Figure 45 Delivering a translational research strategy
Delivering a translational research strategy
Translational programs in
transplantation
Basic stem cell
and
immunology
labs
Translational
labs
Clinical units
Collaboration with industry
Partnership facilitated by
appropriate funding programs
Basic Science Research (Figure 46)
1. In adults, the number of stem cells in a standard cord blood collection is often too small and transplants
regularly require two cord blood stem cell collections. This doubles the cost of cord blood procurement. Thus,
there is an opportunity to reduce cost by developing ex-vivo cord blood stem/progenitor expansion protocols.
This work is still in its infancy with few, if any, molecules shown to provide true stem cell expansion.
2. There is an opportunity to discover new molecules that direct the differentiation of cord blood stem cells
into non-blood cells such as neurons and musculoskeletal cells. This would greatly enhance the prospect of
regenerative therapy.
Figure 46 Developing new stem cell and immune cell based therapeutics
Developing new stem and immune cell based therapeutics
Scientific programs in
stem and immune cell
Clinical units
Collaboration with industry
Translational
labs
Basic stem cell
and
immunology
labs
Collaboration with other
academic funders
Partnership facilitated by
appropriate funding programs
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Part 2: Annexes
Sale of Cord Blood Stem Cells for Academic and Commercial Research
There is a demand for cord blood stem cells for research into pathways involved in diseases with the aim of
identifying of new drug targets. These new drugs could be either be small molecule or biological drugs that bind
key targets to block the pathological pathways, or ultimately could be stem cells themselves that replace a lost
function in the disease. Sale of high quality cord blood stem cells from cord blood collections that are too small
for transplantation would generate additional revenue. Intellectual property on the novel drug targets could be
generated from such research.
Securing Cord Blood Stem Cell Research and Development
Governance
We recommend an oversight committee that would include national/international clinical and scientific experts,
health economists, lay representation and representatives from industry. The creation of such a committee could
be the remit of the UK Stem Cell Strategic Forum. This committee would issue calls for R&D proposals and/or set
aside some funds for response mode funding. Funding would be granted subject to peer review. The committee
would produce annual reports of funds spent and outcomes produced.
Research and Development Funding
We recommend that the oversight committee be charged with securing funding. Funding sources could include
savings made from procurement and delivery of unrelated donor stem cell transplantation and sale of cord blood
stem cells for research. No additional Government money would be required. In addition, the committee should
approach key stakeholders such as NHS Blood and Transplant, the National Institute for Heath and Research, the
Medical Research Council, large medical charities, Anthony Nolan Trust, the Wellcome Trust, the British Heart
Foundation, Arthritis Research UK and directed philanthropic donations should be invited. Different stakeholders
mentioned above may wish to support select opportunities that address the concerns of their constituencies.
Support should be sought from industry. We recommend that working with Regional Centres of Excellence in
Alternative Donor Transplantation the oversight committee should facilitate the development of early and late
phase trials in unrelated donor transplantation and build links between the UK’s world class science base in stem
biology and an integrated clinical trials network.
Liaison with Industry
We recommend a dedicated technology transfer arm is created by the oversight committee to liaise with industry
to define research opportunities and commercialise intellectual property arising from stem cell research: including
patenting, licensing, and even creating spin-out companies. The technology transfer team would also work with
UK academics to allow industry access to experts from the UK’s stem cell world-class, clinical and translational
research base and forge agreements on use of stem cells, derivatives or related technologies in clinical practice.
Finally this team would be responsible for marketing and encouraging access by clinically-focused biotech and
pharma companies.
A Report from the UK Stem Cell Strategic Forum July 2010
79
Annex 11
Performance Managing the Provision of Unrelated Donor Stem Cells for
Transplantation
Summary
The UK’s stem cell supply chain could be performance managed through government-sponsored processes of
commissioning and contract monitoring. This could be steered by a UK Stem Cell Advisory Forum, charged with
practically implementing best practice along the lines suggested by the UK Stem Cell Strategic Forum. This group
would consult and develop protocols on a range of areas, including the size and character of the UK’s adult
donor registries and cord blood banks, regulatory requirements, research priorities, and public and professional
education to improve recruitment. Its remit would include three elements: a national donor registry, a national
cord inventory and a database on patient outcomes. Through a process of contract tendering with precise and
measureable performance indicators, supported by rigorous information gathering, the Forum would oversee a
clear and accountable stem cell supply chain operating within a single national specification.
Commissioning and Contract Monitoring
One way of performance managing the supply of unrelated donor stem cells for transplantation in England may
be via DH (or other government agency)-sponsored processes of commissioning and contract monitoring. This
process reflects that adopted in the US, where the Health Resources and Services Administration (HRSA) invites
provider organisations to submit costed proposals to deliver components of a national stem cell programme.13
A similar approach is here described for England, recognising that provider organisations in Scotland, Wales
and Northern Ireland are subject to different commissioning processes. However, it might be of interest to all
countries of the UK to consider how a commissioning process might benefit processes across the UK, through the
rationalisation of structures and maximising the use of limited resources.
A commissioning process might be supported by a UK Stem Cell Advisory Forum and comprise three elements
namely:
• A national stem cell registry;
• A national cord blood inventory;
• A database of patient outcomes following transplantation.
Under the guidance of the Advisory Forum, the commissioning process might ensure the three elements costeffectively deliver improved patient outcomes through:
• The optimised provision of unrelated adult and cord blood stem cells for transplantation;
• The provision of sufficient and sustainable funding;
• The collection, analysis and reporting of patient outcome data to support the commissioning of clinical
transplantation.
To achieve this, each element would have a contract; the Advisory Forum would assist in the specification of
each contract. Provider organisations would be required to report on key performance indicators annually. The
elements are described briefly below and shown diagrammatically at Figure 47.
Proposed UK Stem Cell Advisory Forum
Purpose
The Forum would develop recommendations to assist the DH (or other commissioning body) in establishing and
overseeing a process to commission the supply of unrelated donor stem cells for transplantation and to monitor
the performance of service providers.
13 http://bloodcell.transplant.hrsa.gov/ABOUT/index.html
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Structure
It is envisaged that the Advisory Forum would build on the work and membership of the UK Stem Cell Strategic
Forum. Members would be chosen to ensure objectivity and balance, and to reduce the potential for conflicts of
interest.
Figure 47 Proposed framework for commissioning and performance monitoring the provision of cord blood and adult donor
stem cells for HSCT
Function
The Advisory Forum would discuss and develop expert, unbiased analysis and recommendations regarding the
supply of stem cells for UK patients. The Forum would develop standards and specify the service levels required
of supplier organisations. These standards and specifications would inform the development of invitations for
‘Expressions of Interest’ from provider organisations. The Forum would support the DH through the collection and
analysis of performance information provided by supplier organisations
The Forum would consult and develop standards and specifications in areas such as:
• The size, composition and quality of the UK adult stem cell donor pool and of a national inventory of cord blood;
• Regulatory and accreditation requirements (in this way defining criteria for facilities, staff and quality assurance);
• Public and professional education to encourage the recruitment of genetically diverse donors;
• Research priorities including the collection, analysis and reporting of patient outcomes following transplantation.
Although the standards and specifications developed by the Advisory Forum would determine service levels in
England through a commissioning/contracting process, it would be expected that provider organisations across
the UK would operate to the same standards.
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81
A UK Stem Cell Registry
In accordance with the findings and recommendations of the UK Stem Cell Strategic Forum, fully costed
expressions of interest might be invited from organisations to:
• Raise awareness and coordinate the optimised recruitment and retention of potential adult stem cell donors
especially those of ethnically diverse backgrounds. Donor recruitment may be outsourced (in full or in part) to
other organisations;
• Undertake (or outsource) testing for infectious diseases;
• Undertake (or outsource) donor HLA typing, maintaining an appropriate archive of donor material and DNA;
• Provide a single point of access to search for unrelated adult donors and cord blood units;
• Provide clinical advice concerning the suitability of donors and cord blood donations;
• Provide an efficient system for collecting samples and undertake confirmatory and extended HLA typing;
• Manage importation of adult stem cell and cord blood donations;
• Provide (or outsource) the collection of bone marrow or peripheral blood stem cells and manage donors
throughout the donation process, ensuring donor safety is a primary concern;
• Support the collection of donor-related outcome data;
• Work closely with third sector organisations to provide educational information for donors, patients, the public,
and medical professionals and to help patients throughout the transplant process;
• Plan for public health emergencies which may require unrelated adult stem cell or cord blood transplants;
• Provide appropriate resilience and disaster recovery measures, including measures to ensure data integrity is
maintained in the interests of UK patients and donors.
The above activities would be performance managed via contract monitoring against a range of indicators
including:
• Size, composition and genetic diversity of the register;
• Registry attrition;
• Donor typing and resolution;
• Turnaround times for the provision of stem cells for transplantation;
• Donor deferral rates;
• Licensing compliance (HTA) and accreditation (FACT-Netcord and WMDA).
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Part 2: Annexes
A UK Cord Blood Inventory
In accordance with the findings and recommendations of the UK Stem Cell Strategic Forum, fully costed
expressions of interest might be invited from organisations to:
• Raise awareness and coordinate the collection of cord blood donations especially those from mothers
of ethnically diverse backgrounds. Cord blood collection may be outsourced (in full or in part) to other
organisations;
• Protect the rights of donating mothers by obtaining appropriate consent to donate and maintaining
confidentiality;
• Undertake (or outsource) testing of infectious diseases;
• Undertake (or outsource) high resolution HLA typing;
• Develop an inventory of up to 50,000 cord blood units within 8 years;
• Provide appropriate resilience and disaster recovery measures, including measures to ensure data integrity is
maintained in the interests of UK patients and donors;
• Provide data cord blood inventory data to national and international registries;
• Plan for public health emergencies which may require cord blood transplants;
• Make cord blood cells available for research.
The above activities would be performance managed via contract monitoring against a range of indicators
including:
• Size, composition and genetic diversity of the inventory
• The dose of cord blood units stored
• Donation typing and resolution
• Turnaround times for the provision of stem cells for transplantation
• Licensing compliance (HTA) and accreditation (FACT-Netcord and WMDA)
A UK Database of Patient Outcomes
In accordance with the findings and recommendations of the UK Stem Cell Strategic Forum, fully costed
expressions of interest might be invited from organisations to:
• Host and maintain a database of donor outcome data and patient outcome data following allogeneic (related
and unrelated) transplantation.
• Work with transplant centres and the donor registry to minimise the effort required to collect and report data
through electronic data interchange.
A Report from the UK Stem Cell Strategic Forum July 2010
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Annex 12
Stakeholder Consultation
At the invitation of the UK Strategic Stem Cell Forum, a stakeholder meeting was convened on the May 14th
2010, with representatives from voluntary organisations, charitable bodies and private cord blood banks to
develop a series of recommendations to present to the Forum. These were presented to the Forum at its second
meeting on May 24th for further consideration.
Summary
To deliver services equitably to UK patients, stem cell providers must communicate with target communities
in a culturally sensitive fashion. Providers should undertake research, in partnership with the third sector, on
public perceptions of donation. Education is another area where the importance of donor registration could be
presented to students, possibly through the official curriculum. This outreach should extend to medical bodies and
personnel to ensure the whole health care system is working with providers on the issue of cord donation, rather
than against them. Providers themselves should ensure recruitment for potential donors is clear and accessible.
Furthermore, the current restriction on donor registration based on age and body mass should be reviewed for
ethnic minority patients to support their increased representation on donor registries.
Recommendations
The following recommendations emerged through workshop discussions.
Stem cell services must be equitable for all UK Patients
Currently, individual patients may receive different level of health care, depending on their PCT. Protocols and
services should be standardised and mandated so that patients receive the same quality of care across the UK. A
‘postcode lottery’ exists for prospective cord blood donors outside London who are currently unable to donate.
Public-private partnerships may have a role in enabling more women to donate.
The importance of donation should be part of the school curriculum.
Schools are an excellent platform to communicate effectively about the value of becoming a donor. The Register
and Be a Lifesaver campaign, drawing on a committed volunteer base, has given presentations to over 8,000
students and has a proven track record in transforming attitudes to donation. However effective, grassroots
initiatives still need support in the form of long term funding and coordination with other services, such as blood
collection.
Beyond this, information on stem cell donation could be introduced as part of the national curriculum, potentially
as part of a larger health education component. Teachers, as well as students, should also be educated on the
central issues surrounding donation. Appropriately designed material could be developed to span the whole
education system, from primary school to university.
Communication strategies should be culturally sensitive.
Recognising and responding to individual perspectives is crucial. Potential donors must be allowed the opportunity
to make free and informed decisions, with a full understanding of what they will involve. Nevertheless, taboos
need to be tackled by engaging with popular fears surrounding areas such as bone marrow extraction and stem
cell research, while raising awareness of the life-saving benefits that donation can bring through transplantation
and research. This needs to be done with sensitivity and tailored to cultural outlooks and community customs.
Charities, teachers, spiritual figureheads, community leaders and private banks all have an important role to play.
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The health system, professional bodies and regulators must encourage and support donation.
Increasing public awareness will have a limited impact without meaningful engagement with the wider health
community, particularly regarding cord blood collection. Organisations such as the Royal College of Midwives,
the Royal College Obstetrics and Gynaecology and the Human Tissue Authority must ensure their policies do not
unintentionally hinder donation. GPs, nurses and antenatal care providers should be encouraged to communicate
to expecting mothers during screenings and consultation about the possibility of cord donation.
It should be easier for donors, especially those from ethnic minorities, to register as a stem cell donor.
Service providers have an obligation to ensure that potential donors are able to navigate recruitment structures
with ease. Clearer signposting during blood donation and in surgeries and clinics is required, supported by
multilingual resources. This is particularly important when approaching expecting mothers from ethnic minorities
for cord collection. This is an area where cooperation with third sector organisations should be exploited.
Donor selection criteria should be reviewed, particularly in relation to potential donors from ethnic
minorities
To raise the representation of non-Caucasians on the UK’s donor panels, current age limitations should be relaxed
to allow mature potential donors from ethnic minorities to register. Height and weight restrictions should be
applied with caution and adjusted to reflect the BMI’s of different ethnic groups.
Research on donor attitudes should to be undertaken by the third sector
Targeted communication strategies for information gathering should be developed. Providers should research
and poll current attitudes and behaviours to accessing stem cell donation information, especially amongst ethnic
minorities with an emphasis on mixed race people and Religious communities. There is an opportunity to provide
patient advocate-led research on how ethnic minorities access stem cell information and become motivated to
register and thus add value to existing research.
Stakeholder Submissions
As part of the review process, stakeholders were invited to submit a short written statement for inclusion in this
report. These are reproduced on the following pages.
A Report from the UK Stem Cell Strategic Forum July 2010
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Submission from Lionel Salama representing The Cord Blood Charity
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Submission from Roger Dainty representing Future Health Technologies
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Workshop Stakeholder Representatives
Orin Lewis and Samantha Walker.
The African and Caribbean Leukaemia Trust (ACLT).
ACLT
The ACLT was founded in 1996 in response to the challenges ethnic minority patients faced in locating a
suitably matched donor. Since then, it has championed a variety of initiatives with a strong community-driven
focus to raise awareness among potential donors and highlight the plight of the many ethnic minority patients
still unable to find a match. In partnership with stem cell providers, such as the ANT, the Trust has been at the
front line of volunteer recruitment. In particular, its strength lies in its ability to deal at a personal level with
fears and taboos surrounding bone marrow and cord blood donation. The ACLT will be directing the extension
of the highly successful ‘Register and Be a Lifesaver’ campaign to schools in the Greater London region.
Keith Sudbury.
‘Register and Be a Lifesaver’ Campaign
The ‘Register and Be a Life Saver’ campaign is an innovative educational initiative, targeted at 17 and 18 year
olds in schools, to raise awareness about the vital importance of registering as a donor. Drawing on a large
volunteer base with a personal connection to the issues, the organisation presents at schools on the vital
importance of voluntary donation. The campaign piloted in South Yorkshire and Bristol, in partnership with
the ANT, and achieved immediate success. Opinion surveys on students before and after the presentation have
highlighted its effectiveness as a low cost donor recruitment tool. Since then, the Register and Be a Lifesaver
campaign has expanded to other areas of the UK and will shortly be launching in London, with the support of
the ACLT.
Tony Gavin.
Former Chief Executive, Leukaemia CARE
Registered as a charity in 1969 and now based in Worcester, Leukaemia CARE has a long history of providing
cancer patients and their families with information and support. In addition to their local network of volunteer
staff, Leukaemia CARE has also developed a range of literature on blood cancers and disorders to assist
patients and their relatives in understanding their disease.
Rebecca Rutter.
Operations Manager, Cells4Life
Cells4Life provides patients with the opportunity to privately bank their baby’s cord blood for potential future
use. It is the only private cord bank in the UK to provide whole umbilical cord storage and has split facilities at
Sussex and Essex for storage.
Roger Dainty.
Director, Future Health Technologies
With laboratory and storage facilities based at Nottingham Science and Technology Park, Future Health
Technologies was the first private family cord blood bank in the UK to receive a full accreditation as a human
tissue bank, in 2004. Future Health Technologies won the Queen’s Award for Enterprise in 2010 in recognition
of its success in securing international business.
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NHS Blood and Transplant
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