FROM CORD BANK TO CORDPHARM ANTHONY NOLAN CORD BLOOD PROGRAMME Expanding access Improving outcomes Opening ways
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THE ANTHONY NOLAN TRUST The Anthony Nolan Research Institute University College London, England
THE ANTHONY NOLAN TRUST Development of the Anthony Nolan Register 1971 - Anthony Nolan born suffering from Wiskott-Aldrich Syndrome 1974 - Donor recruitment commenced to establish a panel of donors 1979 - Anthony died without receiving a transplant 2008 - Number of donor on Reg = 4000,000 2009 - Number of donors provided for transplant = 8020 Jan/2009
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ADULT MODEL: STAIR Allomandatory Jump Sibling MUD Perfect Match Adult Mismatch Quién habla de victoria.? Allotherapy Sobre ponerse es todo Rainer Maria Rilke.??
time a l t e r n a t i v e DRUG / AUTO THERAPY alternatives >30 W 33% 33% Diagnostic 5 W 14 W Allo Sib Allo Sib Tx 19 W 25% unfit 25% no donor UD KING S COLLEGE HOSPITAL NHS TRUST Exploratory No Donor AN Donor Overseas No Tx 21 W Survey 2005 120 Alloprocedures 17% 25% 34% 24% 11 W 60% 10 W Tx UD Tx 26 W 33% 14 W 42% 10 W Tx UD Tx 29 W
Diagnostic Allo Scoring system Urgency HLA yes CB NOD2 MUD MUD Search no CB Search CB CB Search CB Tx 11 weeks time HLA-DP mm MUD Tx >20 weeks CB Tx Objectives: DECREASING TIME INCREASING EFFECTIVENESS
The Large Bone Marrow Registers Name / Total donor / % ABDR typed 23.12.08 NMDP 5,060,482 (86%) Germany 3,355,359 (63%) China Anthony Nolan 395,135 >769,372 (81%) Brazil >554,371 Israel E.M. 399,342 (70%) Italy 326,638 (67%) Japan 320,416 (100%) BBMR 310,541 (94%) Taiwan 277,936 (87%) From BMDW 23/12/08
Total number of HPC donations WMDA report 2007
Unrelated Donor Registers in the UK ANT (1974) - Anthony Nolan Trust 395,135 BBMR (1987) - British Bone Marrow Registry 310,541 759,974 UK donors WBMDR (1989)- Welsh Bone Marrow Donor Registry 54,298 BMDW 23/12/08
UK Activity 2007 1260 new patients referred for searches 704 had their search extended internationally by end of 2007 221 transplants from ANT donors to patients referred from UK centres 75 transplants from BBMR donors and 22 from WBMDR donors to patients referred from UK centres 318 transplants from an international donor/cord unit to UK patients (241 adult 77 CB) 32 UK transplant centres performed at least one unrelated donor transplant (range 1-40)
UK Activity 2008 1414 new patients referred for searches 857 had their search extended internationally by end of 2007 212 transplants from ANT donors to patients referred from UK centres 171 transplants from ANT donors to patients overseas 359 transplants from an international donor/cord unit to UK patients (265 adult 91 CB) 33 UK transplant centres performed at least one unrelated donor transplant (range 1-19)
Source of imported haematopoietic stem cells for UK patients in 2008 - Total 318 77 1 11 11 1 21 3 3 3 4 3 6 81 126 GERMANY USA ITALY AUSTRALIA CANADA CYPRUS FRANCE ISRAEL TAIWAN FINLAND NORWAY AUSTRIA SWITZERLAND SLOVENIA SWEDEN EIRE POLAND PORTUGAL SPAIN CHINA CORD BLOOD
The plan To increase the number of donations provided to UK and international patients such that 1000 patients will be treated with potential life-saving haematopoietic progenitor cells by 2013 and to increase the size of our Register to 450,000 donors
Donor Recruitment Predicted growth of The Anthony Nolan Trust Register 30000 460000 25000 440000 20000 420000 15000 400000 Size of register No of donors deleted No of donors to be recruited Overall size of register 10000 380000 5000 360000 0 2006 2007 2008 2009 2010 2011 2012 2013 year 340000 2.7% increase p.a.
Number of donations facilitated the future No. of donations facilitated by The Anthony Nolan Trust - Future Estimates 1200 1000 800 25% 6% 7% 7% 7% 7% 7% 600 400 200 0 2001 2002 2003 2004 2005 2006 2007 est 2008 est 2009 est 2010 est 2011 est 2012 est 2013 Calendar Year
HLA antigens and alleles 1968-2008
Number of HLA alleles, January 2009 HLA-A HLA-B HLA-C 733(24) 1115(49) 392(9) HLA-E HLA-F HLA-G 9 21 42 HLA-DRA HLA-DRB HLA-DQA1 HLA-DQB1 HLA-DPA1 HLA-DPB1 3 697(20) 34 95 (7) 27 132 HLA-DMA HLA-DMB HLA-DOA HLA-DOB 4 7 12 9 MICA MICB TAP1 TAP2 65 30 7 4
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Low resolution HLA-A*02
Medium resolution HLA-A*0201/09/43N/66/78/88/89/90/91+
High resolution HLA-A*0201/0209
Allele level resolution HLA-A*02010101
B Clinic Research aapc NK N Ste m Cells Co rdpharm Operations Department GIAS Cord Blood Services Adult Blood and Marrow Registry Cord Blood Bank Immunogenetics and Informatics Group ANRI Cellular Immunotherapy Group Immunogenetics ioinformatics aïve T Cells
Allo-option non Drug therapy yes HLA typing non Allomandatory non Drug therapy yes yes Sibling 5/6 Inclusion at AN MUD³ CBT GIAS score CBT>MUD MUD 9/10 CBT 4/6 Note: If a patient need a transplant in a defined time (urgencies), the donor available at this moment will be used
Scoring System: Proposal 1) Expected outcome of search: Individual frequencies Pair frequencies: DR-DQ, B-C Haplotype frequencies 2) Selection between 2-donors: Donor MUD CBT MAJOR HLA compatibility HLA compatibility CMV donor NC/CD34 dose Age donor Need for DLI MINOR Gender CMV recipient Previous pregnancies Fact accredited bank P. Blood vs BM Duration storage
The Anthony Nolan Cord Blood Programme Register Cell Pharmacy Cord Blood Bank Cord Blood Pharm
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BONE MARROW DONOR REGISTERS: EFFICIENCY QuickTime and a TIFF (Uncompressed) decompressor EFFICIENCY/YEAR ~ 1/1000 QuickTime and a TIFF (LZW) decompressor DONOR RATIO % 0.096 0.106 0.102 0.100 0.088 0.090 0.090 0.081 0.089 0.079 QuickTime and a TIFF (LZW) decompressor RECIPIENT Cost: Inventory (150): 57,000,000, Transplant (4000): 14,250
QuickTime and a TIFF (Uncompressed) decompressor EFFICIENCY/YEAR ~ 1/1666 QuickTime and a TIFF (Uncompressed) decompressor Cost: Inventory(150): 679,000,000, Transplant (25,000): 27,180
EFFICIENCY: ~1/100 QuickTime and a TIFF (Uncompressed) decompressor Cost: Inventory (1,500): 206,000,000, Transplant: 37,784
Maintenance Cost UNRELATED DONOR AVAILABILITY Building phase (charitable) Cord= 50,000 ~ 75,000,000 MUD= 500,000 ~ 75,000,000 PROBABILITY 100 80 60 40 20 10e4 8&8 6&6 5&6 4&6 0 1,0E+07 1,0E+06 1,0E+05 1,0E+04 1,0E+03 1,0E+02 1,0E+01 1,0E+00 DONORS REGISTERED CB OPERON 75% 4/6 45% 5/6 100000 Maintenance phase 10000 Blood: needs 5000 ~ donors 5000/100,000 (500,000 )= cost 100 MUD: needs 3 but supply 1 ~ donors 100/100,000 (15,000 ) = cost 15,000 Cord: needs 3 ~ donors 3/100,000 (4,500 ) = cost 1,500 1000 100 10 Blood Cord MUD 1 0 1 2 3 4 Phase
Impact of cell dose and HLA Match on survival. Data presented by Dr Pablo Rubinstein at the 5 th International Umbilical Cord Blood Symposium held in Los Angeles in May 2007. Survival 5/6 Match 4/6 Match 5/6 match 4/6 match Cell Dose ( 10 7 /kg) 70% >10 50% 5.0-9.9 30% <2. 5 2.5-4.9 <2.5 time after transplant
% Probability Of Patient Match Sample 2000 Patients 100 90 80 70 60 50 40 30 20 10 0 1 10 100 1000 10000 50000 100000 150000 Match 4 of 6 5.5 16.5 48.25 78.5 94.6 98.25 99.55 99.9 Match 5 of 6 0.65 2.45 11.5 35.75 63.8 79.5 85.55 90.45 Match 6 of 6 0 0.05 1 6.55 19.25 34.05 41.35 45.15 Donor Sample Size
ANTHONY NOLAN CORD BLOOD PROGRAMME CordBank Cord Blood Bio-resource Donor Registry Cord Blood Transplantation Research Bank Stem Cell Biology Transplantation Immunology CordPharm Medicinal By-Products Cellular Stem and Immune Cells Non-Cellular RBC, Plasma, Platelets TheraCord New Therapies Haematology Adoptive Cell Therapy Non-Haematology Regenerative Medicine Tolerance
QuickTime and a TIFF (Uncompressed) decompressor QMP QuickTime and a TIFF (Uncompressed) decompressor Collection Storage Intelligent labeling SOP Register ID (confidentiality) RELEVANT DATA (critical steps) seal ELECTRONIC RECORDS transport ANCB FACTORY QC clinical data QuickTime and a TIFF (Uncompressed) decompressor Recep Proces Cryopres LT Storage freezer ship log Transport Directive 2004/23/EC and its technical requirements HTA FACT-NETCORD Grade C CD34/CFU IDM/ MICROBIOLOGY BLOOD TESTS QuickTime and a TIFF (Uncompressed) decompressor Clinical analysis
NTU Service Provider contract Building Security Maintenance Generall cleaning IT support Clean Modules Ltd Service Provider contract Maintenance COURIER Service provider Distribution KINGSCORD TPA Procurement contract SLA CB Human applications Testing Processing Storage Distribution ANCTC-NTU Cord Blood Research Research cord blood bank London LABS ANT Central Support IT H&S HRs Fundraising Marketting Operations & Registry Distribution Import/Export Financial contract contract contract Waste Company Service Provider BIOSAFE Service Provider CRYOSERVICE Service Provider Testing contract contract BD Flow Service Provider Testing BD BacTec Service Provider Other suppliers: Coulter, General Equipment, GMP-cleaning, Micronclean, others
Anthony Nolan Cord Blood Programme BANKING Automation Graft QualificationAN QuickTime and a TIFF (Uncompressed) decompressor COLLECTION Ethical Logistics Hospital CBB FACTORY CB RECRUITMENT AN REGISTER CB TRANSPLANT. DONOR SELECTION GIAS Search algorithm TRANSPLANTATION Gold standard: conditioning, follow-up, engraftment, chimerism Immune reconstitution KingsCord QuickTime and a TIFF (Uncompressed) decompressor CORD BLOOD BIOBANK bedside Multiple Donors: engraftment and immunotherapy Multi-donor Tx (pooling) Selection/Expansion New products: CD34/CD133, Naïve T regs, USSC/MSC, CELL THERAPY Neural ANCTC bench Associated groups Automation Data Management BIOINFORMATICS Cardiovascular Liver Basic Biology Orthopaedics
Cord Blood Bank 10,000 clinical units 10,000 Research cord units Cellular Immunotherapy Group CordPharm Stem cells for Tolerance induction T reg Stem cells for Cardiovascular intervention aapc for cord blood cell manipulation NK, Naive Investigating Engraftment of stem cells
ANCBB GIAS Wharton Club Tolerance Cord Blood Research Programme NIHR Adaptive Innate aapc Stem BMT Immuno Immunogenetics Genetics Programme BioInformatics Oxford Cardiovascular UCL Engraftment CIH ALLOSTEM 1 AND 2
As a SERVICE Biopharmaceutical perspective Stem cell therapy Cell lines Regenerative Medicine Health Investment Affordable commodity for a new stem cell biomedical industry
THE ANTHONY NOLAN TRUST Organizational Chart Mr SM Dyson Chairman Mr T Farnfield Finance & Admin. Director Mr D Knights Marketing & Comm. Director Mr G. Parkes Fundraising Director BOD Trustees Mrs H. Braund Chief Executive P. Makoni Operations Director Dr S Querol Cord Blood Bank Director Prof JA Madrigal Research & Scientific Director Research Institute Anthony Nolan Joint Scientific and Medical Advisory Committee Prof J Goldman Medical Director
ANTHONY NOLAN CORD BLOOD BANK (ANCBB) ANT BOD Corporate License Holder Advisory Committees (AC) ANCBB-AC Chair: Prof Madrigal ANCBB-MANAGEMENT Dr Steve McEwan, Rep License Holder Prof Goldman, Prof Madrigal, Dr Little ANT Central Services CU-AC Chair: Prof Mufti KingsCord Third Party Agreement Head-Cord Blood Services Dr Sergio Querol, Designated Individual Quality Supervisor IT Supervisor H&S Supervisor CB Provision and Transplantation Distribution KINGSCORD-MANAGEMENT KCH representative: Prof Mufti Medical Officer: Dr Dennes Operations: Katie, Winsome, Frank CB Bank & Lab Manager Anthony Nolan Cell Therapy Centre, NTU Collection Unit (CU) Supervisor Ms Terie Duffy, Person Designated Trained KCH Staff Bank Supervisor Lab Supervisor CB Bank & Lab Technicians ANT Round Table Labs Procurement Testing, Processing, Storing Organisational Chart (MSP-R-5, v3, 10/6/08)
Liver ANTU-NCH ccbbb: core Cord Blood bio Bank as a translational research model for cell therapy Creating a new scientific environment Heart / Neural Lung Bench ccbbb bedside Kidney Basic Science KingsCord GIAS
ANTHONY NOLAN CORD BLOOD BANK QuickTime and a TIFF (Uncompressed) decompressor Robert Davy, Roger Horton East Midlands Development Agency Laura Fry, Daniel Gibson, Salmah Mahmood Susana Garcia Gomez Hazel Forde, Kamal Khan, Peter Chenery Richard Duggleby, James Devitt Daniel Figueroa, Lia Zambetti, Mehri Daryouzeh Prof Tony Dodi Dr Steve Marsh, Dr Bronwen Shaw Dr Ann Margaret Little, Dr Steve McEwan Prof Robert Rees Terie Duffy, Maria Tarrio Katie Yannouzis Dr William Dennes Winsome Okeke Dr Antonio Pagliuca Prof Ghulam Mufti QuickTime and a TIFF (Uncompressed) decompressor QuickTime and a TIFF (Uncompressed) decompressor Prof John Goldman Dr Sergio Querol Prof Alejandro Madrigal Prof Nigel Russell Dr Joan Garcia QuickTime and a TIFF (Uncompressed) decompressor QuickTime and a TIFF (Uncompressed) decompressor