UK Stem Cell Strategic Forum Recommendations

C Craddock, University of Birmingham

Our Aims and Objectives

The UK Stem Cell Strategic Forum was established at the request of the Minister of State for Public Health in February 2010.

Led by NHS Blood and Transplant. To deliver a comprehensive strategy to meet the needs

of UK patients for unrelated haemopoietic stem cells. Working with stakeholders, service providers, experts to:

Understand the healthcare and economic challenges of alternative donor transplantation

Find new ways of working together to save and improve patients’ lives.

Allogeneic stem cell transplantation remains the only curative therapyfor children and adults with high risk haematological malignanciesInitially confined to patients with matched sibling donors but excellentoutcomes now achievable using unrelated and cord blood donors

Major barriers limit the extension of a curative option to all:

Absence of a suitable donor-particularly affects patients from BME communities

Delays in identifying a suitable donor Death from transplant toxicity or disease relapse Lack of a coordinated UK strategy to deliver alternative donor stem cells and

high quality transplant care

Historic opportunity to increase number of lives saved by Tx and establishthe UK as a leader in stem cell provision and transplant

An important opportunity to improve patient outcomes

Stakeholder Engagement

Review structured to be as inclusive as possible – hence Working Groups supporting the Forum.

Other ‘Reference’ Groups established as required to further draw on available expertise and opinion.

Key stakeholder engagement via workshop and/or briefings:

Orin Lewis - The African Caribbean Leukaemia Trust (Chair) The Cord Blood Charity The Jeanette Crizzle Trust The Adrian Sudbury Campaign Desi Donors Private cord blood banks The All-Party Parliamentary Group on Umbilical Cord Blood

and Adult Stem Cells

Requirements and Benefits Group

Professor David Marks (chair) – consultant transplant physician Dr Mary Horowitz (Head CIBMTR, USA) Prof Eliane Gluckman (Hospital St Louis, Paris) Dr Fred Appelabuam (Fred Hutchinson Cancer Centre, Seattle

USA) Dr Paul Veys - consultant transplant physician Dr Sergio Querol - consultant transplant physician Dr Derwood Pamphilon – Medical Director BBMR and NHS-CBB Stephen Dobra - DH Principal O.R. Analyst Dr. Rachael Hough - Chair BSBMT CB Working Group Dr Paresh Vyas – Research and Development Kate Bingham - Schroder Venture Capital

Service Delivery Group

Dr Andrew Hadley (chair) – Review co-ordinator Dr Carlheinz Müller – Director, German Bone Marrow Registry Henny Braund – CEO Anthony Nolan Trust Lynda Hamlyn – CEO NHSBT Colin Pavelin – Department of Health Dr Derwood Pamphilon – UK Blood Services Dr Kieran Morris – NI Blood Transfusion Service Dr Geoff Poole – Welsh Blood Service Keith Thompson – Scottish National Blood Transfusion Service

Commissioning Group

Prof Antonio Pagliuca (chair) – President BSBMT Dr Jackie Cornish – Consultant Transplant Physician Mike Millen – Specialist Commissioner Cathy Edwards – Specialist Commissioner Jessica Whitton, Commissioning Manager, South West

specialised Commissioning Group

Unanimous agreement that stem cell transplantation from either unrelated donors or umbilical cord blood are highly effective treatment strategies for children and adults with high risk leukaemia and other haematological disorders

There is a clear and important need to significantly decrease the time it takes to identify suitably matched unrelated donors. This can be achieved through better tissue typing of volunteer donors and exploitation of information technology platforms which assist in the prediction of patient-donor compatibility

Key Recommendations

Improve the Provision of Unrelated Adult Donor Stem Cells

To increase the number of UK patients finding an acceptable match within a clinically appropriate time period, we recommend that:

In collaboration with third sector organisations, there should be greater engagement with Black and minority ethnic donors to increase their representation on donor registries and cord blood banks.

Selected donors should be retrospectively and prospectively HLA typed to high resolution to obviate the need for this test as part of the donor selection process

Recommendations

The UK should create or purchase predictive search technologies (such as those used by German and US registries) to increase the chance that selected donors are a match for the patient

A ‘graft identification advisory service’ should be established to ensure optimal donor selection for each patient.

Registries should increase contact with donors, updating information on their contact details, health status and willingness to donate.

These measures are intended to create a ‘fit panel’ of volunteer donors. Collectively, they would:

Increase the proportion of selected adult volunteers able to donate from 60% to 90%

Reduce the number of donor searches by around 30%

Reduce the number of extended HLA typings performed at donor selection by 75%

Reduce search to transplant times by four to six weeks.

Given the unique ethnic diversity of the UK investment should be made to establish a bank of 50,000 cord blood units accessible to all NHS patients

Importation of cord blood units from international registries cannot substitute for the development of a UK cord blood inventory

Stem cell dose is a critical determinant of outcome after cord blood transplantation and target doses should be kept under continual review

Key Recommendations

Stem Cell Supply Recommendations

Improve the Provision of Cord Blood Stem Cells

Based on an analysis of transplantation trends, and of patient and donor Demographics, we recommend that:

The UK should increase its inventory of cord blood to 50,000 units over eight years. This time period represents a cost-effective approach to achieving the required inventory.

The inventory should contain 30% to 50% of donations from Black and ethnic minority women.

Newly banked units should have a high total of nucleated count threshold (over 9x108 TNC from ethnic minority donors, over 12x108 TNC from Caucasian donors).

Outcomes

Satisfy 85% of unmet Caucasian need (around 150 patients each year) and 50% of unmet black and minority ethnic need (around 50 patients each year).

Improve search to transplant times (around 100 patients each year who fail to receive an adult stem cell transplant due to delays in provision would be able to be transplanted).

Improve donor/recipient matches (around 70 patients each year transplanted with a 9/10 matched adult donor could be transplanted faster or more effectively).

Reduce the total cost of cord blood units to the NHS to £16K- investment cost neutral within 5 years, saves money to the NHS beyond that.

Provision of Cord Blood Stem Cells

Unrelated donor transplants are complex treatments with a substantial treatment-related mortality. Regional Centres of Excellence for unrelated donor transplantation, specifically cord blood transplantation, should be established in order to improve patient outcomes. Any savings from this rationalisation should be considered for re-investment in the stem cell transplant programme of the NHS

A system should be put into place for all units performing unrelated donor transplants to report immediate and long term patient outcomes to Commissioners through a national transplant outcome registry.

Key Recommendations

Drive Quality and Efficiency

Unrelated donor transplantation should reflect clinical best practice. Acknowledging differences in policy across the UK, we recommend that:

Educational tools and platforms should be developed to improve understanding among commissioning bodies. With the support of physicians, commissioners should align their strategies with the latest clinical guidance and patient outcome data.

Commissioning bodies should operate within a standardised funding framework, using a baseline figure adjusted to reflect market forces factors. This should detail the necessary costs for each stage of the patient’s treatment to provide clarity and certainty to all service providers.

Allograft activity by UK transplant centre, 2009

Cord transplant activity by centre, 2009

Resources and expertise for cord blood transplantation should be concentrated into designated Regional Centres of Excellence, promoting high quality care and the best use of resources.

• Regional Centres of Excellence should serve a minimum population of 4-5 million.

Local networks should be linked into designated centres and make appropriate referrals when necessary.

Drive Quality and Efficiency

Standardised data collection and outcome monitoring should be integrated into every stage of the patient pathway so that reliable outcome data can be used to benchmark individual performance and promote best practice.

Funding streams should be identified to support the collection and analysis of outcome data from Regional Centres of Excellence.

Given the significant mortality of unrelated donor transplantation it is highly desirable that transplants are performed according to disease specific registration studies and where possible appropriately badged clinical trials

Commissioning authorities should encourage the development of appropriate studies for patients undergoing unrelated donor transplantation

Key Recommendations

Substantial Government funding over the last two decades has resulted in the development of a world-class science base in stem cell biology in the U.K. A clinical trials network of centres performing unrelated donor stem cell transplants should be established. This will create one of the world’s largest stem cell transplant trials networks

Collaborative links should be established between donor registries, cord blood banks and the biopharmaceutical industries. This initiative, coupled with the establishment of a clinical trials network has the capacity to attract inward investment in the U.K which will create jobs in the knowledge rich biotechnology sector

Key Recommendations

The LLR Trials Acceleration Programme

Structure

Drive Quality and Efficiency

Designated transplant centres should work together to support an alternative donor clinical trials network

The commissioning process should encourage the development of registration studies and early and late phase clinical trials in alternative donor transplantation

Funding streams should be identified to develop this important translational initiative

All recommendations of Report accepted by Dept of Health

Identified by Ministers as a model of collaborative working between clinicians, commissioners and providers

£4 million grant provided to NHSBT and AN for expansion of unrelated donor registry and cord blood bank

Effective collaboration between NHSBT and AN has delivered a single registry, grown a fit panel and enabled expansion of unrelated registry and cord blood bank

Progress to date

Jan 2012: Rebid to fund further expansion of registry and bank and secure funding of outcome registry submitted to DoH

Joint NHSBT/AN graft identification services workshops established in order to share best practice

Active discussions with Commissioning authorities to deliver Regional Centres of Excellence

Request for support for transplant trials network, in the context of 2011 Govt Life Sciences Review, submitted to NIHR

Strategic Oversight Committee tasked with long term review and development of UK policy for alternative donor stem cell transplantation

Progress to date

Back Up

Unrelated donor HSCT trends worldwide

The increasing use of unrelated donor HSCT in older patients

The increased use of cord blood in the UK for unrelated donor HSCT

Patient matching rates by ethnicity (2004/5)

Search times for bone marrow donations and cord blood units