The future of unrelated Stem Cell Transplant in the UK: DOH Working Party Findings Prof. Tony Pagliuca
UK STEM CELL STRATEGIC FORUM The future of unrelated donor SCT in the UK Antonio Pagliuca, Transplant Director King s College Hospital, London EBMT (UK) NAP GROUP 40 TH MEETING 30 th June 2011
Background The UK Stem Cell Strategic Forum was set up at the request of the Minister of State for Public Health in January 2010 To advise on future options for the provision and use of stem cells derived from unrelated adult volunteer donors and cord blood Also to be seen in the context of London Cancer Services: a proposed model of Care, commissioning models July 2010 Harmonisation of processes and costs The report, July 2010, was the result of three months of intensive effort by over forty scientists, clinicians, economists, and patient representatives
UK STEM CELL STRATEGIC FORUM Review areas The Healthcare Benefits of Unrelated Donor Haemopoietic Stem Cell Transplantation in the UK The Provision of Stem Cells for Transplantation in the UK Meeting the Demand for Stem Cells in the UK Increasing the Availability of Adult Donor Haemopoietic Stem Cells for Transplantation Increasing the Availability of Cord Blood Units for Transplantation Supply Chain Options for Improving the Availability of Donor Stem Cells in the UK Financial Appraisal of Options to Reconfigure the Supply Chains Health Economic Analysis The Commissioning of Unrelated Donor Stem Cell Transplantation in the UK The Value of Research and Development In Unrelated Donor Stem Cell Transplantation and Regenerative Medicine Performance Managing the Provision of Unrelated Donor Stem Cells for Transplantation Stakeholder Consultation
Global Distribution of Hematopoietic Stem Cell Transplantations (HSCTs) in 2006 Gratwohl, A. et al. JAMA 2010;303:1617-1624.
Macroeconomic Factors and Transplant Rates UK Transplant Rate per 10m inhabitants Team Density teams per 1m inhabitants Gratwohl, A. et al. JAMA 2010;303:1617-1624.
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 in adults
Types of stem cell donation transplanted by country and the use of cord blood in unrelated HSCT
Worldwide trends in the national and international provision of stem cell donations for HSCT
The proportion on stem cells sourced from UK and overseas donors
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%
Patient matching rates by ethnicity (2004/5)
Relationship between matching rate and size for large European donor registers
OUTCOMES
Rates and outcome of HSCT according to HDI Giebel S et al, Blood April 2010
UD UCBT CENTRE EFFECT DFS BY NUMBER OF TRANSPLANTS PERFORMED 1,0,8,6,4 > 10 transplants: 35 5% at 2 yr,2 P = 0.004 < 10 transplants: 20 4% at 2 yr 0,0 0 12 Months 24 36 Eurocord, unpublished.
Number of transplants Adult HSCT since 2004 UK only 500 450 SIBLING UNRELATED CORD AUTO 400 350 300 250 200 150 100 50 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 Centre
Number of transplants Adult Allografts since 2004 UK only in Descending Order 400 350 300 TOTAL SIBLING UNRELATED CORD 250 200 150 100 50 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 Centre
Geographic concentration of adult and paediatric transplant activity in the UK, 2009 ADULT PAEDIATRIC
Example of Commissioning Responsibilities Blood and Marrow Transplantation Responsible Party Non-specialised commissioners Specialised commissioners Non-specialised commissioners Pathway Elements All pre-transplant activity up to and including the point of decision to transplant Stem cell harvesting for patients for whom a definite decision to transplant has not been made Autograft Phases 1 to 4 Allograft Phases 0 to 6 and Donor Lymphocyte Infusion if appropriate All subsequent follow up activity following post transplant discharge EXCEPT where a new transplant package of care is instigated Commissioning Currency Routine activity funded at national tariff Locally determined tariffs for the package of care Routine activity funded at national tariff
Treatment Phases-Autograft AUTOGRAFT PHASE 1 -Decision to Transplant, Pre Transplant Mobilisation/ Stem Cell Harvest/Manipulation Storage &Pre Transplant Assessment PHASE 2 -Patient Work up inc disease assessment. PHASE 3 -TRANSPLANT ADMISSION / EPISODE - Conditioning regimen/management of Pancytopenic phase and regeneration. PHASE 4 -Discharge to 100 day follow up PHASE 5-100 day to 1 Year follow up (not included in costing calculations)
Treatment Phases-Allograft ALLOGRAFT RELATED/UNRELATED PHASE 1 -Decision to Transplant, patient assessment, Investigations, Donor Matching /Selection / Testing / Tissue Typing PHASE 2 -Patient & Donor Work up PHASE 3 -Donor Harvest including Stem cell manipulation & may include provision of GCSF/ Patient work up etc PHASE 4 -TRANSPLANT ADMISSION Conditioning regimen & Stem cell infusion. Management of pancytopenic phase and Graft vs. Host disease. PHASE 5 -Occasional Requirement for repeat Stem Cell Infusion with / without Chemo if graft failure occurs
Treatment Phases-Allograft cont. PHASE 6 - Discharge to 100 day follow up including management of acute - graft versus host disease / infections and other complications PHASE 7-100 days onwards, Management of Complex Issues; Graft vs. Host disease, secondary Malignancy, opportunistic Infections, excludes Donor Lymphocyte Infusions (not included in costing calculations) PHASE 8 - Donor Lymphocyte Infusions (not included in costing calculations)
Associated Tariffs- 2010/11 International Supplement BMT Type Cost model Tariff 10/11 ( ) Antifungal price per transplant Donor Tissue Typing Average cost per transplant Donor Costs Average cost per transplant Total price per transplant Autologous* 29,888 1,631 31,519 Allogeneic related Allogeneic unrelated 46,336 4,622 3,813 5000 59771 77,914 6,110 3,813 13750 101587 DLI 7,279 7297 Example from London consortium with MFF
Funding Allocation Phases Autos Allo Related Allo Unrelated 1 17% 22% 3% 2 10% 5% 3% 3 63% 10% 9% 4 10% 48% 70% 5 No Data No Data 6 15% 15% 7 Example: If the charge covers only the period up to discharge then the following should be deducted from the prices in the earlier table, all other things being equal: Phase 4 for Auto (10%) Phase 6 for Allo (15%) Taken from Consortium Costing Model Guidelines Nov 2009
Proposed framework for commissioning and performance monitoring the provision of cord blood and adult donor stem cells for HSCT
The Findings Each year in the UK, about 170 Caucasian and 90 black and minority ethnic patients fail to locate a suitably matched adult donor. Around 110 patients with a matched donor die or deteriorate beyond transplantation while waiting to be transplanted. Improved access to adult unrelated donors and cord blood donations will cure around an additional 1000 people of an otherwise fatal condition over the next ten years
The Recommendations Adult Donors Greater engagement with black and minority ethnic donors Selected donors should be HLA typed to high resolution The UK should introduce predictive search technologies A graft identification advisory service should be established Increase contact with donors
The Recommendations Cord Blood The UK should increase its inventory of cord blood to 50,000 high dose units (8,000 currently at NHS-CBB). The inventory should contain 30% to 50% of donations from black and ethnic minority women (40% currently). Newly banked units should contain over 90 x 10 7 TNC (ethnic minority donors) or 120 x 10 7 TNC (Caucasian donors). High resolution HLA typing should be performed on newly stored units and selected existing units.
The Recommendations Transplantation Streamline registry activities in the UK Educate commissioners on patient outcomes Cord blood transplantation should be concentrated into designated Centres of Excellence Data collection and outcome monitoring should be integrated into every stage of the patient pathway Designated transplant centres should work together to support an alternative donor clinical trials network A Stem Cell Advisory Forum should build on the work and membership of the UK Stem Cell Strategic Forum
The Case for Investment Autumn 2010 Ministerial support for recommendations and a request for NHSBT and Anthony Nolan to develop a joint bid for funding. November 2010 - business case requests 50.1m over 5 years. Proposal to: a) align NHSBT and Anthony Nolan registry activities b) bank 50,000 cord blood donations over 5 years c) improve provision of adult donors via high res. typing & matching algorithm Separately, NHSBT is: a) implementing operational improvements in BBMR b) implementing EMDIS (July go live) c) HLA DRB1 typing existing cord blood donations
Additional Funding of 4m for 2011/12 Ministerial announcement during January 2011 of 4m funding in first instance. NHSBT and Anthony Nolan proposing a collaborative framework which will see: UK transplant centres accessing NHSBT stem cell donors via the Anthony Nolan register Anthony Nolan and NHSBT ramping up cord blood collection and banking to 24/7 Anthony Nolan and NHSBT investing in high resolution typing of selected existing adult donors and cord blood donations http://www.nhsbt.nhs.uk/pdf/uk_stem_cell_strategic_forum_report. pdf www.nhsbt.nhs.uk/pdf/uk_stem_cell_strategic_forum_annex.pdf