Att. 2
A Strategy for the Development and
Commissioning of Haematopoietic Stem Cell
Transplantation Services in Wales
February 2008.
1
1)
Introduction
The purpose of this document is to offer a replacement the current commissioning policy
issued by Health Commission Wales (HCW) in October 2006 and in doing so provide
more informed guidance on the application, governance and performance aspects of
Haematopoietic Stem Cell Transplantation Services.
2)
Clinical Context
For a variety of inherited and acquired, malignant and non-malignant, haematological
and non-haematological conditions, a successful haematopoietic stem cell
transplantation (HSCT) represents the only means of cure.
HSCTs fall into two main categories: autologous, where the patient acts as their own
donor; and allogeneic, where the donor is either a family member or unrelated
volunteer. Recent improvements in tissue typing has now led to almost identical
survival in patients receiving an unrelated but fully matched transplant compared to
matched family members.
The source of haematopoietic progenitors has traditionally been bone marrow but this
has recently been superseded by peripheral blood stem cells for all categories of
transplant. More recently umbilical cord blood from both related and unrelated donors
has been shown to be a suitable alternative to bone marrow for both children and adults
who lack a suitably matched conventional donor.
Traditionally it was thought that only transplantation following myelo-ablative
conditioning chemo-radiotherapy would be beneficial but from the late 1990’s there has
been increasing reports of the successful use of reduced intensity allogeneic transplants
such that this is now a standard recommended form of transplantation. As the
conditioning therapy is markedly less intensive than previous it has significantly
increased the number of patients suitable for an allogeneic procedure e.g older patients,
those with co-morbidities (EBMT Annual Surveys 2000 – 2005; Gluckman et al, NEJM
1989;321:1174-8; Kurtzberg et al, NEJM 1996;335:157-66; Rocha et al, Blood
2001;97:2962-71; Laughlin et al, NEJM 2004;351:2265-75; Rocha et al, NEJM 2004;
351:2276-85).
HSCT activity in Europe and the UK
The European Group for Blood and Marrow Transplantation (EBMT) show that there has
been an exponential increase in the number of transplants performed in Europe over the
past 30 years. In 1975, 14 transplants were recorded and by contrast, the EBMT
recorded over 25, 000 ‘first’ transplants and nearly 29, 000 total transplants in 2006
(Gratwohl et al, BMT 2001;27:899-916; Gratwohl et al, BMT 2007; EBMT Activity Survey
2006).
The majority of transplants performed today are autologous and account for
approximately 60% of transplant activity in Europe. Although the increase in HSCT
activity has largely been due to the expansion of autologous transplantation, particularly
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for myeloma and lymphoma, there has also been an increase in allogeneic
transplantation.
Compared with 2004, there was a 20% increase in allogeneic HSCT in Europe in 2005,
whereas autologous HSCT remained relatively constant. The most significant increase
was in unrelated donor HSCT which comprised 41% of allogeneic activity (Gratwohl et
al, BMT 2006). Data from the UK and Eire, collated by the British Society for Blood and
Marrow Transplantation (BSBMT) showed similar trends with allogeneic transplant
activity rising by 17% in 2005 compared with 2004 and with unrelated donor HSCT
accounting for 49% of allogeneic activity in 2005 (BSBMT Annual Surveys 2004, 2005).
3)
Current Provision in Wales
Within Wales HSCT for adults is provided by three centres, University Hospital Wales
(UHW), Cardiff, Swansea NHS Trust and North West Wales NHS Trust at Bangor. Further
services are provided outside of Wales in Manchester, Liverpool and Bristol.
3.1 The UHW service
A purpose-built 6-bedded unit was opened in 1986 with 20 cases being funded,
subsequently funding was increased to support 50 transplants per annum.
Between 1985-1994, a total of 350 HSCTs were performed, equivalent to a mean of 35
per annum. For the subsequent 10-year period 1995-2004, 545 HSCTs were performed
– an increase of 55.7%. This increase in HSCT activity continues, with 64 and 70
transplants being performed in 2005 and 2006, respectively. It should be noted that
additional funding was received in mid-2006 to help alleviate waiting list pressure.
As expected, an increase in autologous transplantation has been primarily responsible
for the increase in transplant activity. Two hundred and fifteen autologous HSCTs were
performed in 1985-1994 representing 61% of HSCT procedures performed that decade,
rising to 412 (76%) for the period 1995-2004. In stark contrast with international
trends, allogeneic transplantation remained constant with 135 and 133 procedures being
performed in each of the above decades, respectively (Table 1).
Table 1. HSCT procedures performed at UHW: 1983 – 2006
TIME PERIOD
HSCT
TYPE
1983-84
1985-89
1990-94
1995-99
2000-04
AUTO
0
58
157
235
177
ALLO
8
65
70
65
68
TOTAL
8
123
227
300
245
2005-06
71
63
134
The unrelated donor HSCT programme was re-introduced in 2002. After the initial startup years the number of unrelated HSCTs is now equivalent to sibling HSCTs, effectively
doubling the number of allogeneic HSCTs performed annually (Table 2).
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Table 2. Allogeneic HSCT at UHW according to donor type: 2000 – 2006
YEAR OF HSCT
DONOR
TYPE
2000
2001
2002
2003
2004
2005
Sibling
14
12
08
12
10
19
Unrelated
00
00
03
05
04
12
TOTAL
14
12
11
17
14
31
2006
15
17
32
In 1999 UHW participated in a multi-centre phase II trial evaluating the efficacy of RIC
HSCT in a range of haematological disorders (Dasgupta et al, BMT 2006;37:455-461).
As a consequence of this study there is now an active RIC HSCT programme at UHW
and RIC allografts now account for an increasing proportion of allogeneic HSCTs (62.5%
in 2006)-Table 3.
Table 3. RIC’s HSCT at UHW 2003-2006
2003
2004
2005
2006
12
6
16
13
3.2
2007 to
date
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The Swansea service
The autologous stem cell transplant service in Swansea NHS Trust was started in the
latter part of 1997. The clinical haematology services for patients requiring inpatient
chemotherapy care in Swansea NHS Trust is centralised in Singleton Hospital on Ward
11 next to the oncology inpatient service on Ward 11/12. The SCT unit on Ward 11 is a
two laminar flow unit with own nursing station and other facilities.
The mobilisation of the stem cells for these patients is carried out in the Haematology
Department in Swansea. Patients will then travel as a day case for stem cell collection
(harvesting) in Cardiff. Harvested cells are stored in Cardiff until needed by the stem
cell unit in Swansea.
Patients are admitted to Singleton Hospital for their conditioning regime with high dose
chemotherapy, this is carried out in one of the two Laminar airflow units on Ward 11.
Infusions of the harvested stem cell are carried out according to an established protocol
and the patients are kept in isolation until their recovery.
The services started in the last quarter of 1997. To date, 79 patients had high dose
chemotherapy and autologous SCT. The number of transplants are presented in table 4.
Table4- Stem Cell Transplant (Bone Marrow and Peripheral Stem Cell) activity
in Swansea
Years of SCT
1997-98 1999-2000 2001-02 2003-04 2005-07
Autologous SCT
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16
14
19
20
4
3.3
The North Wales service
Autologous transplantation started in Bangor in 1992 using single rooms on the
Haematology Ward until the new Alaw Unit opened in 1999.All donor selection,
harvesting and storage is carried out in Bangor whilst mobilisation, high-dose therapy &
re-infusion takes place at both Bangor and Glan Clwyd using common protocols. The
laboratory and storage facilities at Bangor achieved MHRA accreditation in 2006 and the
service is working towards JACIE accreditation currently.
Table 5 .HSCT workload across N.Wales.
Patients
BM Harvests
PBSC Harvests
Reinfusions
1992 – 97
44 (all YG)
36
8
18
1998 – 2003
79 (YG + YGC)
12
219
66
2004 – 2007
91 (YG + YGC)
6
110
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There are plans to extend the autologous service to patients from Wrexham in 2008 as
part of the Networked approach to Haematological malignancy in North Wales.
Allogeneic transplantation has always needed to be referred out of North Wales.
Traditionally this was to Liverpool for Glan Clwyd & Bangor and the Christie Hospital,
Manchester for Wrexham. More recently, Glan Clwyd has tended to use the Christie
rather than Liverpool and Bangor has tended to refer to Bristol, especially for younger
patients and cases of severe aplastic anaemia.
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4.
Current Challenges to the HSCT service in Wales.
From a comparison of the three sites and the HSCT activity to date a number of issues
can be identified that need to be addressed if the service is to progress.
4.1
Physical capacity
A significant challenge to the UHW service is the outstripping of capacity by current
demand resulting in an increasing waiting list. At present an average of 8 patients are
referred for HSCT each month and at current referral rates (and transplant indications),
the programme needs to be able to accommodate at least 86 patients per annum to
prevent further growth of the waiting list.
Given the rise in allogeneic transplantation at UHW it would be possible to develop
Swansea as a site for autologous transplantation with potential capacity of more than 20
transplants per year and serve the whole of West Wales vacating beds for allogeniec
transplants at UHW. This would require a change of clinical practice as at present
patients requiring autologous transplants from Aberwystwyth, Carmarthen, Haverford
West and Llanelli are still referred to UHW.
North Wales will have its own autologous service for all three sites based on the current
Network though there is an issue of storage capacity for frozen stem-cells which may
involve a small capital spend at Bangor. There are also potential issues of in-patient bed
numbers for autografting in the Alaw Unit.
4.2. The provision of an Unrelated Donor Transplants.
There has been a large rise in the indications for unrelated HSCT and UHW has
undertaken 41 unrelated donor transplants – a figure which is not only rapidly rising but
likely to increase at an even faster rate as the acceptance of this form of therapy for low
grade tumours becomes more widely appreciated.
It is clear that given the very low level of unrelated transplants performed in mid/north
Wales that there is almost certainly inequality of access for this type of transplant. There
needs to be a clear strategy for meeting this at present unmet demand.
4.3
The provision of Reduced Intensity Transplants.
As with unrelated donor transplants there has been a marked increase in indications for
RIC’s. At UHW the demand for this type of transplant is rising rapidly and in 2006 it
accounted for 62% of all allograft procedures. As with unrelated donor transplants there
needs to be a clear strategy for meeting this at present unmet demand.
RIC transplantation has been under-used in North Wales and the demands need
properly assessing to see whether they would be best met by service level agreements
with English trusts or by developing the existing autologous service.
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4.5
Assuring the quality of services
The challenge for all three SCT centres is the achievement of JACIE accreditation.
5.
Future Commissioning of the HSCT service for Wales
The commissioning process should ensure that,
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5.1
appropriate patients are considered for HSCT based on recognised clinical
evidence
services used meet appropriate levels of quality and safety
a suitable framework is developed to address capacity issues and changes in
practice
Clinical Pathways
Clinical pathways will differ by primary disease, type of transplant and location. However
understanding some core elements of the clinical pathway is essential to the
commissioning process as elements of the pathway can be delivered by different
organisations with different levels of service and different commissioning arrangements.
As a consequence each pathway should be identified for each part of Wales – see table
6.
Table 6.
Common elements of a HSCT pathway
Pathway element
Potential location
Initial remission induction Unit level
chemotherapy
Decision to transplant
Unit/ centre level
Donor selection
Harvesting
Unit/ centre level
Centre
Storage
Centre
Conditioning
Re-infusion
Centre
Centre/unit level
Post infusion recovery
Centre/unit level
Follow up
Centre/unit level
Notes
Depends on primary disease
MDT discussion that should be joint
with HSCT centre
Dependent on procedure identified
May include donor and procedure.
Blood stem cell harvesting may
include multiple visits
A percentage of stored blood and
bone marrow may not be used and
may be stored for future use
Chemotherapy work up
Optimum location is at centre to
reduce risks.
Dependent on time post infusion, well
being post infusion, type of
transplant, psychological status and
facilities
Can be performed in either subject to
protocols
Providers of HSCT services should identify to commissioners annually the clinical
pathways for HSCT in their locality naming the organisations involved and their
role within the pathway.
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5.2)
Service specification
In order to be commissioned as a provider of a BMT service the following elements of
the service must be in place and maintained. Key factors identified below directly relate
to the ‘ International Standards for Cellular Therapy Product Collection, Processing and
Administration’ FACT –JACIE (3RD Edition – Feb 2007) and are also in line with NICE IOG
and the Welsh Cancer Standards.
5.2.1)
Activity
A service providing allogeneic transplantation should perform a minimum of 10 new
patient procedures per annum with no minimum number for autologous transplants
being required if performed within the same unit.
A service providing solely an autologous HSCT service should perform a minimum of 5
new patient procedures per annum.
A breakdown of activity must be provided 3-monthly and a summary provided
annually
5.2.2)
Facilities
Inpatients
Inpatient facilities must be of a nature to minimise airborne microbial contamination with
a minimum requirement being single bedded, private accommodation with en suite
sanitary facilities. Such facilities must be provided for the remission induction, bone
marrow re-infusion and marrow recovery phases of the pathway.
Laminar flow, HEPA filtration facilities are desirable for allogeneic HSCT services but are
not required for an autologous HSCT service.All facilities must be supported by a
protocol for environmental hygiene e.g. room cleaning, filter cleaning/replacement
schedule. Adherence to this protocol should be audited annually.
Facilities supporting an allogeneic programme should ideally be able to support mobile
renal dialysis facilities.
Day case/outpatients
Dedicated outpatient and day case facilities should exist that are designed to,


minimise infection risk
facilitate IV drug and blood product administration
- Facilities should be described once and changes notified annually.
- Audit of environmental hygiene measures should be provided annually.
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5.2.3) Programme Management
The Clinical Transplantation Programme must be under the leadership of a single
Programme Director with an agreed deputy both of whom are deemed to have adequate
experience for the role, as agreed by the relevant Cancer Network.
The Clinical Programme Director will
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Be responsible for the administrative and clinical functions of the service
Have oversight of all elements of the clinical programme including quality
management, selection and care of patients and donors, cell collection and
processing (internal or contracted out)
Have oversight of all medical care and the proficiency of those delivering that
care
Have oversight of the clinical care delivery by the transplant team (MDT)
Programme Director confirmed annually
5.2.4) MDT structures and personnel
The HSCT service must be supported by a sustainable HSCT related multi disciplinary
team (MDT) who function both in a virtual and physical manner to identify and deliver
the optimum care for the patient.
The MDT must identify the following members and the cross cover/deputisation
arrangements,
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Lead clinician and deputy who have adequate clinical experience of HSCT ( as
indicated by JACIE)
Junior and senior clinicians providing 24hr on-call
Lead nurse for in and out patient /day case setting
Microbiologist
Virologist
Radiologist
Pharmacist
Dietician
Social worker
Psychologist
The full MDT should meeting regularly to discuss, if appropriate, patients undergoing
HSCT, patients being worked up for HSCT and patients post HSCT under follow up. If
patients are being followed up at unit level, where appropriate, these patients should be
discussed at the request of the unit level team.
Patient discussion at the MDT should be supported by a protocol that as a minimum
confirms the decision making process and communication of that decision to the patient
and clinical team
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If not meeting to discuss patients the full MDT must meet to discuss outcomes, service
issues, audit and the ongoing delivery of the service. The frequency of these review
meetings will be at the discretion of the programme lead but must be frequent enough
to ensure adequate clinical governance is achieved.
Annual confirmation of MDT membership and MDT meeting
timetable/attendance
5.2.5) Support Staff and Facilities
A requirement of a service providing allogeneic transplantation must be immediate
access to,
`
 designated renal expertise and dialysis facilities on site, preferably within the
HSCT unit
 accessible HDU/ICU care if not integrated within the HSCT unit
Mechanical ventilation facilities should be accessible on site and supported by a protocol
for the management of patients ventilated off site and away from the HSCT setting.
For units providing an autologous transplantation service only the above is desirable but
not essential.
Evidence of problems with access to renal/HDU/ICU facilities and expertise annually
Nursing and Allied Health Professions
The nursing team should,
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Be of a size adequate to ensure that staffing levels are safe and appropriate at
all times.
Have a greater nurse to patient ratio in allogeneic HSCT units
Have enough flexibility to ensure 1:1 nursing where patients are severely ill
Demonstrate core skills pertaining to IV administration of chemotherapy and
other drugs via central lines and management of blood disorders
Be proficient in cardio-vascular monitoring
Have an adequate skill mix to ensure that experienced, post graduate qualified
nurses are in place on each shift
Have in place a rolling programme of post graduate education relevant to HSCT
Those Allied Health Professions involved in the care of HSCT patients should as a
minimum be designated staff. Post graduate education should be provided for those
staff designated to the MDT.
Annual self assessment of nursing profile
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5.2.6) Transfusion and laboratory services
The service should have the ability to access CMV appropriate blood products as well as
irradiated blood products, where indicated, at all times. In the eventuality that such
products are not available alternative blood products should only be used according to a
previously agreed protocol.
In the case of an allogeneic HSCT service access should also be made available to HLA
DNA – based typing.
A protocol must be in place to support the transfusion of patients who, undergoing
allogeneic HSCT, experience, as a result a change in blood group.
- Description of access to transfusion services and details of access to
CMV/irradiated blood products and annual confirmation.
- Submission of transfusion protocols.
5.2.7) Pharmacy services
Access must be available to pharmacy services at all times.
Pharmacy input into the MDT should come from a designated member of staff who is
able to respond in an informed way to the themes pertaining to pharmaceutical
management of HSCT patients.
Description of access to pharmacy
5.2.8) Clinical policies
The Programme Director together with key MDT members must ensure that the HSCT
service is supported by evidence based clinical management and administrative
protocols/policies.
In addition the Programme Director should ensure that these protocols/policies are
audited frequently and re-visited at least every 3 years.
As a minimum there must be policies and protocols regarding,
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Chemotherapy administration and spillage
Environmental management of the immuno compromised patient
Clinical and laboratory monitoring of the patient
Clinical use and management of blood products
Use of prophylactic anti infection measures and growth factors
Clinical management of neutropaenic sepsis
Post discharge precautions
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It is noted that a prerequisite of JACIE accreditation is evidence of protocols/policies
covering a wide range of issues and the list identified above should not be considered
exhaustive.
All HSCT units should be seeking to obtain JACIE accreditation by 2010.
Evidence of progress towards JACIE accreditation provided annually.
5.2.9) Follow up
Immediate follow-up (day 0 – 100) should be conducted at the transplant centre in
facilities co-terminus with the HSCT unit itself.
Where follow up is delivered prior to day 100 at a local unit it should only be done so
through agreement between the programme director and the local unit level clinician. If
this follow up arrangement exists it then should be supported by a suitable protocol.
Part of the agreed protocol must ensure that,
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The unit level clinician is ‘integrated’ into the BMT MDT
Immediate access to the BMT services is ensured
The unit level facilities are adequate for the management of the patient
Long term follow up over and beyond day 100 can be performed at unit level but should
be supported by a suitable protocol.
Communication between the BMT centre and the unit should be considered of a
standard adequate for the unit to
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Provide follow up in an appropriate, safe and integrated manner
Provide emergency interventions as required
Provision of protocols for emergency care, immediate and long term follow up
Provision of a standard for communication between the BMT centre and units
5.3)
Information
Data collection must be an integrated part of the BMT service and all MDT personnel
should recognise their individual role in collecting adequate data.
The Programme Director should work with colleagues across Wales to ensure common
data items are collected. Key items of data that must be collected and reported on
annually include,
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Primary diseases, and phases of diseases transplanted
Types of transplants performed
Donor selection
Length of disease free survival
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All complications in first 100 days (including episodes of infection)
All deaths within first 100 days
Long term/delayed side effects
Patient support including information for patients from units
Commissioners require three sets of performance information,
a)
A response to the measures identified within this commissioning guidance
document - Annual.
b)
Completion of the annual audit of activity against the Wales Cancer Standards.
c)
Numbers of patients waiting for BMT identifying primary disease, disease status,
time waiting, predicted BMT date, point on clinical pathway ( donor search, bed
awaited) - Quarterly.
Clinical information should be submitted to the BSBMT data register annually.
Information summary should be provided quarterly and a summary annually
5.4)
Clinical Research
As many patients as possible should be offered the opportunity to be submitted into
recognised clinical trials
6)
The Commissioning Process
The present process in Wales is manifestly failing. Welsh patients do not receive an
optimal service for the following reasons:
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Lack of an overall strategic plan for delivery & development of the SCT service in
Wales.
Inefficient utilisation of existing services.
Unequal access to resources as evidenced by the matched unrelated donor &
reduced intensity transplant data quoted above.
Unacceptably slow and inconsistent decision-making in individual cases.
The present system excludes the clinical experts who provide the service and this has
led to a lack of meaningful engagement between the commissioners and the clinicians.
There is an urgent need to bring the parties together in a body empowered to address
the following issues:
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1. The development of a sustainable, equitable service for the whole of
Wales based on and benchmarked against the standards of care in the
rest of the UK & Europe.
2. The prioritisation of resources for future development plans.
3. To agree the indications for transplantation.
4. To manage demand and capacity issues.
5. To set and monitor standards of care.
6. To directly advise the Welsh Assembly Government on a specialist and
rapidly changing field.
7. To review requests for SCT that fall outside routine indications and
advise the Minister in a timely fashion of their appropriateness.
A suggested membership for such a body would be as follows:
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The Chair of the Cancer Services Coordinating Group or a nominated deputy.
The Chairs for Haematological Cancer in the three Cancer Networks in Wales.
The Programme Directors of the 3 Transplant Centres in Wales.
The Medical Director of the Commissioning Body.
The Financial Director of the Commissioning body or a nominated deputy.
The Cancer Network Directors or their representatives. .
A Patient representative.
This group would be responsible for:
1. Providing a strategic plan.
2. Managing the budget & allocating resources.
3. Negotiating with English Trusts for services provided.
4. Updating the indications for transplant that are deemed the best standard of
care.
5. Authorising Patient Pathways.
6. Monitoring JACIE accreditation progress.
7. Producing an annual report for WAG of future advances & developments.
8. Providing a sub-committee to adjudicate in a timely manner on difficult cases.
Standards of Care would be monitored by the 3 Programme Directors producing:
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3-monthly reports on progress with JACIE.
3-monthly reports on activity.
Annual reports on outcome & adverse events.
Proof of Annual submissions to EBMT registry.
Evidence of MDT meetings
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6.1)
Patient selection process
All BMT procedures conforming with the standard indications for transplantation as
described by BSBMT 2008 (see appendix 1) will be automatically supported when
ratified by the relevant MDT. Those indications described as “Clinical Option” that have
been accepted as best clinical practice by the All-Wales group described above will also
be supported automatically. Cases falling outside these groups will be referred to the
Adjudication Sub-Committee – see below.
6.2
Adjudication Sub-Committee
This is
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
a sub-committee of the main committee consisting of the following:
The Chair of the main committee.
The Medical Director of the Commissioning Body
At least 2 of the following:
Haematology Network Chairs and/or
Transplant Programme Directors
Who are not directly involved in the particular request.
A Finance Commissioner should be present but not voting to ensure information
on the decision is processed rapidly.

The requesting Physician or Programme Director will provide evidence for the request
with particular emphasis on the following:
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Clinical appropriateness
Clinical safety and risk
Assessment of outcome
Value
The Adjudication Sub-Committee will be convened within 10 working days and review
the evidence and may either:
- agree to support
- agree not to support
- request additional information
a. In writing from the Physician/Programme Director and/or
b. External experts – eg. Programme Directors elsewhere.
In the event of the Sub-Committee being unable to reach a decision the Chair will
present the evidence directly to the Minister for a final decision.
Decisions to support or not support will be notified to the relevant Programme Director
within 5 working days of the decision. Requests for additional information will be
required within 5 working days and the sub-committee reconvened.
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