Overview of OneMatch, including the OneMatch Public Cord Blood Bank

Transcription

1 Overview of OneMatch, including the OneMatch Public Cord Blood Bank Dr. Heidi Elmoazzen, Director OneMatch Public Cord Bank

2 Outline Overview and Introduction Overview of the need for stem cells and OneMatch Stem Cell and Marrow Network OneMatch Public Cord Blood Bank model Current activities and next steps Cord blood banking process 2

3 Stem Cells/OneMatch Stem Cell & Marrow Network A Canadian Blood Services line of business 11 th largest registry in the world Accredited and active member of the World Marrow Donor Association (WMDA) 3

4 At The OneMatch Network, We Recruit and maintain the Canadian national registry (OneMatch Stem Cell & Marrow Network) Search for potential voluntary unrelated donors for Canadian and international patients Screen potential unrelated donors Coordinate the collection of stem cells in Canada and around the world 4

5 OneMatch Fast Facts August 2012 Searchable donors: 333,371 Canadian Transplant Centres: 18 Canadian Collection Centres: 10 International Registries: 76 Over 19,838,863 registrants worldwide International Cord Blood Banks: 48 Over 542,858 umbilical cord blood units Francis, OneMatch Registrant 5

6 How are donors and patients matched? Stem cell matches are determined according to markers on white blood cells called Human Leukocyte Antigens (HLA). A buccal (cheek) swab sample is collected and several of these HLA s are typed by DNA-based methods. 6

7 Diagram of HLA Inheritance 7

8 Three Matching Scenarios Canadian Donor for Canadian Patient International Donor for Canadian Patient Canadian Donor for International Patient 8

9 Number of Patients Canadian Patient Searches Demand and Need Continues to Increase All Patient Ethnic Origins /05 05/06 06/07 07/08 08/09 09/10 10/11 11/12 Total 9

10 300 Canadian Patient Transplants using Canadian and International Donors YTD ( ) Marrow PBSC Cord

11 Canadian Stem Cell Recipients Canadian Unrelated Transplants International Donor Canadian Donor /03 03/04 04/05 05/06 06/07 07/08 08/09 09/10 10/11 11/12 11

12 Canadian Unrelated Donors Canadian Unrelated Donations International Patient Canadian Patient /12 10/11 09/10 08/09 07/08 06/07 05/06 04/05 03/04 02/03 12

13 Ethnic Composition of OneMatch Network 13

14 Recruitment (New HLA Typed Registrants Added) /04 04/05 05/06 06/07 07/08 08/09 09/10 10/11 11/12 Total New Registrants New Registrants <40 New Ethnic Registrants 14

15 Age Composition of OneMatch Females % Females % Males % Caucasian Males % Ethnic Males % Males %

16 More Optimal Donors Needed Continuing with routine recruitment efforts will not fully support patient needs OneMatch, along with its internal and external partners, must focus on recruiting optimal donors for our Transplant Centres and our patients in need

17 Why are young males, considered optimal donors? More likely to be selected because of their size Increased potential for better post-transplant outcome (less graft vs. host disease, better chance of engraftment) CMV negative donors more likely to be young

18 Why are young males, considered optimal donors? Survival rate statistically significant at one year when product from younger donor (NMDP study) The greatest gap in finding matches is with ethnically diverse patients The largest registries in the world have significantly more young males and therefore OneMatch is often not the registry of choice we need to change this 18

19 Why are young males, considered optimal donors? Better investment at registration if donors are on the Network for longer OneMatch has a preset funding envelope - focusing on ethnically diverse males brings best value for health care funding provided 19

20 Where Canadian donations go (2004/2005 to 2011/2012) Percentage of Canadian Exports 25% 20% 15% 10% 5% 0% 20

21 Where International products come from (2004/2005 to 2011/2012) Percentage of Stem Cells Imported 40% 35% 30% 25% 20% 15% 10% 5% 0% Germany United States United Kingdom France Italy Spain Taiwan Belgium Australia Israel Other 21

22 Canadian Patients Transplanted Using Cord Blood Stem Cells Cord Blood Transplants /03 03/04 04/05 05/06 06/07 07/08 08/09 09/10 10/11 11/12 Hema-Quebec Cords Cord Blood Transplants 22

23 Need for Additional Stem Cells OneMatch is an active member of the International Network of stem cell registries and on behalf of all Canadian patients needing a stem cell match, we search and have access to: 19.8M potential adult donors from 66 registries in 48 countries; and, 543K public CBUs from 46 cord blood banks in 30 countries. source: BMDW, September 7, 2012 However, even with this access, we are still only able to find matches for about 50% of patients AND it is harder to find matches in many ethnic groups due to under-representation on registries worldwide. With the continued significant increase in demand and Canada s unique and large ethnic diversity, there is significant need for a national, public cord blood bank. 23

24 Canadian Aboriginal Recipients Registry data ( ): 102 recipients identified as aboriginal 40 transplanted (39%) 2 full HLA match, rest various degrees of mismatch 7 from Canadian donors Median time to transplant 8.2 months Vs. 5.8 months for non-aboriginal recipients Note 10 searches still active as of Dec 2011 and 1 in work up 50 searches cancelled 24

25 Need for Additional Stem Cells US National Marrow Donor Program: AABB million donors on registry Adds 1 million per year to registry Rate of 8/8 match (HLA A B C DRB1) Caucasian 80% Asian 30 40% South Central American Black 15% Due to under representation in donor pool AND increased diversity in the minority groups 25

26 Need for Increased HLA Diversity Increasing donor number has less impact vs pre 2004 Duplication of common haplotypes Need to increase less common haplotypes even more so than common ones Eg assume equal registry size probability of match if African ancestry = 30% vs 60% in non Africans Due to HLA diversity WITHIN the population NMDP

27 Cords and Ethnic Diversity Higher likelihood of match as only 6/6 required HLA A B DR US NMDP data 150,000 CBU and add 25,000 per year Likelihood of 6/6 match European descent: 15% adult recipient, 35% child Likelihood of 4/6 match 75% in ALL adult populations Virtually all children in all ethnic groups 27

28 Need for a National Public Cord Blood Bank An increasing majority of all unrelated paediatric stem cell transplants in Canada are performed using cord blood and there has been and increase in the adoption of cord blood for adults (two cords used). Cord blood has distinct advantages over bone marrow or PBSCs: More lenient HLA matching requirements With current inventories 95% of children will have at least a 4/6 HLA antigen matched unit With adequate cell dose outcomes similar for 4/6 vs 6/6 HLA matches Banks can be adjusted to increased ethnic (HLA) diversity Units are available immediately (1 day 2wks vs 3 10 mos for adult stem cells) Lower risk of graft-vs.-host disease (GvHD) Minimal risk to donor (mother and baby) All cord blood units supplied by Canadian Blood Services for unrelated transplant are imported from international sources. The cost of importing cord blood units continues to increase $42,000 ea. Uncoordinated, multiple banks cannot meet the need for a HLA diverse inventory that is required for Canadian patients. 28

29 Official Announcement March 14, 2011 Ministers of Health announce Canada's first national, publicly-funded umbilical cord blood bank $48 million investment over eight years. Please note: $12.5M of the $48M will be raised over three years by Canadian Blood Services fundraising campaign. April 1, 2011 OneMatch Public Cord Blood Bank project began in Ottawa, as per approved model by the Ministers of Health April 2, 2013 Go-live in Ottawa Spring 2014 Go-live in Edmonton, Vancouver and Toronto 29

30 OneMatch Public Cord Blood Bank Model Includes at least four collection cities and two manufacturing facilities for processing, storage and distribution. Please note: We will also be working on cord blood collection kits that can be sent to targeted areas outside of cities listed below to reach Aboriginal communities, for e.g. Canadian Blood Services OneMatch National Public Cord Blood Bank (inventory of 20,000 units within 8 years*) Medical and Scientific Advisory Committee Searching, Matching OTTAWA Manufacturing Facility (April 2, 2013) EDMONTON Manufacturing Facility (2014) CBS Support HLA Testing Transmissible Disease Testing CBS Research Ethics Committee (units unsuitable for transfusion) Marketing & Recruitment *Optimal size of a national cord blood inventory is currently estimated to be approximately 20,000 units, which can be achieved within eight years using this Model. Canadian Transplant Programs International Registries OTTAWA Collection Hospital(s) (April 2, 2013) TORONTO Collection Hospital(s) (2014) EDMONTON Collection Hospital(s) (2014) VANCOUVER Collection Hospital(s) (2014) Canadian Research Scientists 30

31 Cord Blood and Research Approximately 20% to 40% of the cord blood units collected are of sufficient volume and/or cell count to be used for transplantation. Donors will have the option to designate their cord for research in Canada if it cannot be used for transplantation. Working with stakeholders to ensure a comprehensive system is in place for Canadian researchers to access cord units in a rational, fair and transparent manner CBS Research Ethics Board Canadian Stem Cell Network Canadian Blood and Marrow Transplant Group 31

32 Informed Consent Established a collaboration with Dr. Bartha Knoppers (McGill University) to: Develop an informed consent protocol for cord blood donation for research for the OMPCBB Develop content for an information pamphlet for potential UCB donors for research. June 2012 Stakeholders Workshop Gain an understanding of stakeholders perspectives around donor consent of UCB for research Inform stakeholders about the OMPCBB Establish relationships between stakeholders across Canada to build long-term trust and to strengthen the community of experts 32

33 Workshop In partnership with 20 experts including researchers and clinicians from across Canada and

34 Scope and Timelines The Canadian Blood Services OneMatch Public Cord Blood Bank will consist of collection sites (hospitals) in Ottawa, Toronto, Edmonton and Vancouver, with processing and storage sites at our two existing stem cell manufacturing facilities in Ottawa and Edmonton. The goal is to reach a minimum of 20,000 cord blood units in storage for transplantation by March 31, 2019 eight year period beginning April 1, Phase I of the cord blood bank will be operational in Ottawa in April 2, 2013, and in the remaining sites, Phase II, in FY 2011/12 FY 2012/13 FY 2013/14 FY 2014/15 Ottawa Collection & Manufacturing Edmonton Collection & Manufacturing Vancouver Collection Toronto Collection PHASE I PHASE II PHASE II PHASE II 34

35 Cord Blood Banking Process Seven key processes for cord blood will include capturing and centralizing data on a per unit basis for traceability, searching and matching, information management, ad-hoc queries, reporting, data export and modeling for optimization. Awareness Recruitment Collection Receiving, Assessing, Processing, Testing, Storage Searching, Matching Distribution Transplant, Follow-up Stem Cell Application Solution 35

36 Awareness Marketing Objectives 1. To develop strategy to raise awareness of the public cord blood bank among prospects to facilitate recruitment 2. To implement tactics to support recruitment 3. To develop strategy for donor recognition 36

37 Recruitment Our target group is specific and localized, i.e., healthy pregnant women who plan to deliver at the designated collection hospitals: Discussions begin during the antenatal period with their health care professional Education, information gathering, questions (becoming informed of process in advance of day of delivery) Arrive on special day with Permission to Collect form ready No advance registration 37

38 Maternal Information Booklet 38

39 Collection Three Collection Methods 1. Ex-utero: Fully supported by CBS OMPCBB designated staff 2. In-utero (supported): All aspects of collection, labelling, packing/shipping by hospital staff CBS OMPCBB Nurse Specialist for maternal interview 3. In-utero(non-supported): Entire process completed by hospital staff. This model is intended for future remote sites e.g. northern Canada. The Ottawa Hospital April 2, 2013 General Campus: Ex-utero Civic Campus: In-utero (supported) 39

40 Manufacturing Ottawa Stem Cell Manufacturing Facility (40 Concourse Gate): Peripheral Blood Apheresis / Bone Marrow: Processing, testing, storage, distribution New Manufacturing Area 2004 Four manufacturing areas 2000 sq. ft. FACT Accredited / GMP Guidelines Staffing: Charge Technologists and MLTs Manufacturing Equipment 40

41 Receiving & Assessing From collection site to manufacturing facility Process control / inventory control / tracking CBS Transport / selected courier Assessing: Acceptability criteria Volume, blood cell counts, visual inspection, pre- manufacturing sample Maternal blood samples: TD testing 41

42 Processing Sepax System Fully-automated, mobile, GMP compliant system for the efficient and reproducible processing of umbilical cord blood, bone marrow and peripheral blood Hands-free operation automated, closed, sterile system Quick, accurate data tracking Consistently high mononuclear cell recoveries 42

43 Quality Control Testing Blood cell counts (Pre and Post) Purity, Potency, Safety Purity: Microbiology Potency: Stem Cell Counts Flow Cytometer (CD34+ count) CFU Assay (stem cell culture) Safety: Genetic screening, infectious disease testing QC samples storage 43

44 Cryopreservation Volume reduced cord blood unit Cryo-protectant added (DMSO) Controlled rate freezing using ThermoGenesis BioArchive freezer Holds up to 3,636 units Liquid nitrogen storage (-196 C) Inventory controlled / tracked Must be stored within 48 hours of collection; can be stored indefinitely 44

45 Searching and Matching Listed on OneMatch Registry Banked inventory of cord blood units Cords listed, searched and requested Searched both nationally and internationally OneMatch Stem Cell National Systems Solution (IT system) Physicians / Clinical Transplant sites request OneMatch banked cord blood unit Build on current OneMatch process 45

46 Distribution Requested Cord Blood for Transplant Manufacturing selects, releases, packs and ships Transport courier 46

47 Transplant and Follow-up Transplant Follow-up: Outcome Measurement Build upon the current OneMatch process Infusion Reactions Engraftment Data 100 day follow-up Family History Genetic 47

48 The Selection and Acquisition of Unrelated Cord Blood Grafts Dr. Juliet Barker et al, Blood 2011; 117: Transplant centres want to know about factors that influence the graft potency (i.e. volume, TNC, CD 34 + ) They want to know IDM are negative They want to be ensure the unit is matched They want to know the unit comes from an accredited bank They want to know their patient will not acquire a genetic or serious disease 48

49 Canadian Datacord Data What are Canadian TC selecting? Adults 2010 average TNC per single cord recipient = 2.7 X 10 9 (range ) n = 7 average TNC per double cord recipient = 4.60 x 10 9 (range ) n = 3 Adults 2011 average TNC per single cord recipient = 2.70 x 10 9 (range ) n = 12 average TNC per double cord recipient= 2.70 x 10 9 (range ) n = 3 Pediatrics 2010 average TNC per single cord recipient = 1.77 x10 9 (range ) n = 7 average TNC per double cord recipient =3.20 x 10 9 (range ) n = 3 Pediatrics 2011 average TNC per single cord recipient = 1.88 x 10 9 (range ) n = 16 average TNC per double/triple cord recipient = 4.04 x 10 9 (range ) n = 6 Infants 2011 less than 2years average TNC per single cord recipient = 1.26 x10 9 (range ) n = 11 double cord recipient TNC = 2.35 x 10 9 n = 1 49

50 Double Cords: Still high TNC Adults 2010 average TNC per each CBU = 1.69 x 10 9 (range ) Adults 2011 average TNC per each CBU = 1.35 x 10 9 (range ) Pediatrics 2010 average TNC per each CBU = 1.21 x 10 9 (range ) Pediatrics 2011 average TNC per each CBU = 1.86 x 10 9 (range ) Infants 2011 TNC for each CBU = 1.27 x 10 9 and x

51 TNC threshold: International Perspective Center or Organization Minimum Volume* Minimum TNC* Plan to increase threshold* Different cutoff for ethnic non dominant* CD 34+* Houston MD Anderson 40 ml 0.9 X X New York 40 ml 1.4 X Florida Life Cord 40 ml 1.5 X X 10 9 Cleveland Switzerland X Spain X Geneva X X 10 9 Paris X 10 7 Anthony Dolan CBB # X X 10 9 Barcelona # 2.0 X x 10 6 if TNC x 10 9 Eurocord 1.0 X 10 9 Taiwan 80 ml 0.8 x

52 IDM s are Negative Standard IDM testing as per CBS blood donor and OneMatch donor testing Testing in line with Health Canada, FACT and FDA regulations HIV, Hep B, Hep C, WNV, 52

53 Ensure the Unit is Matched This is best done using an attached segment In theory, rapid HLA-typing can be performed on thawed unit Banks risk compromising the unit if testing needs to be repeated for each request and then the unit is not used 53

54 Does the Unit Come From an Accredited Bank? AABB NetCord-FACT Jacie Other issues: turnaround time Speed of responses Reliability of unit information Fees for unit testing 54

55 Want to Ensure that the Patient Will not Acquire a Serious or Genetic Disease Hemoglobinopathy screen Thalassemia Sickle Cell Newborn screening programs Medical history of mother and family Social, travel and medical history Follow-up information regarding babies health Voluntary and scheduled follow up 8 week and 1 year follow up letter 55

56 Current Activities: Collection Facility Readiness The Ottawa Hospital Civic & General Campuses June 27, 2012 TOH Civic renovations completed MOU signed by TOH July 12, 2012 First cord blood collection, in-utero, for the OneMatch Public Cord Blood Bank. Transported to Ottawa manufacturing site and put through entire process from receiving to storage. Over 51 collections completed to date. September 14, 2012 TOH General renovations completed Ex-utero collections to begin Left to right: Dr. John Lamensa, OBGYN; Dr. Aisling Clancy, PGY 2 OBGYN; Tiffany Lawless, Canadian Blood Services Nurse Specialist; Angie Gill, RPN (OR); Gail Cunningham, RN 56

57 Current CBU Metrics (note: small sample size; for directional, not definitive use) 51 CBUs collected since July 12, Civic campus: Ethnicity: 65% (33) Caucasian 19% (10) Mixed (eg., Chinese/Caucasian, Sri Lankin/Brazilian) 12% (6) Other (eg., Jamaican) 4% (2) Not listed 34 CBUs of the 51 (14 sent for Sterility Study; 3 insufficient data): TNC of 1.5x10 9, or above (pre-processing): 32% Average shipping temperature: 22 C (range = 21.1 to 23.7 note: must be within 15-25) Average volume: 107ml (range = 46 to 205) 57

58 Current CBU Metrics (note: small sample size; for directional, not definitive use) Chart: Correlation between ml collected and TNC Table: To date, lowest volume to achieve TNC of 1.5X 10 9 or greater is 89ml Collection CBU Volume (ml) Pre-TNC X ml Pre-TNC 58

59 Other Cord Blood Activities Edmonton Manufacturing Facility Facilities renovations and human resources Regulation/Accreditation Health Canada Registration FACT/NetCord Accreditation AABB Accreditation Documentation Processes Data Requirements Procedures (i.e., SOPs) Forms (i.e., Consent) Validation Collecting in Ottawa to validate/test all processes and equipment Hospital Selection RFP selection process to begin in Oct and hospitals to be notified by Dec 59

60 Cord Blood Project Team Sue Smith, Executive Director, Stem Cells Dr. Heidi Elmoazzen, Project Director Dr. David Allan, Medical Director Dr. Tanya Petraszko, Medical Director Karen Mostert, Manager, Recruitment & Collections Mike Halpenny, Manager, Stem Cell Manufacturing & Hospital Services Todd Campbell, Project Manager 60

61 Thank you 61