CORD BLOOD History and Future

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• CORD BLOODHistory and Future
• Presented by Carolyn T. Young, M.D.
• Vice President and Chief Medical Officer
• Rhode Island Blood Center

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CORD BLOOD

• Stem cells generate various cell lines
• Sources of stem cells bone marrow, peripheral
  blood (after stimulation), and umbilical cord
  blood
• These sources can generate hematopoietic and
  mesenchymal cell lines
• Committed cells may generate other tissue
  specific cell lines

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CORD BLOOD

• Rich source of stem cells from all ethnic groups
• Readily available
• 1988 First successful cord blood sibling-sibling
  transplant was for Fanconis anemia
• May treat many diseases including leukemia,
  lymphoma, sickle cell anemia
• Estimates of the risk of needing stem cell
  transplant range from 11000-1200,000 per ACOG
  and AAP

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CORD BLOOD

• Current thoughts
• Indefinite storage frozen in liquid nitrogen
• Perfect HLA match is not needed unlike marrow
  transplants
• Increases the probability of finding an
  acceptable donor cord blood
• Less Graft vs Host Disease in transplanted
  recipients

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CORD BLOOD

• Best predictor of engraftment is the total
  nucleated cell count present in the original
  collection, i.e. cell dose
• The more donor cells per recipient weight the
  better chance of successful engraftment
• Limitation of size of recipient, lt40 kg, for
  single cord transplants
• Increases the probability of finding an
  acceptable donor for transplant since the HLA
  match does not need to be identical

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CORD BLOOD

• Future thoughts
• Many adult leukemia patients may be eligible for
  umbilical cord blood transplantation by using
  multiple cord bloods
• Research done combining two units, median dose 35
  million nucleated cells/kg, found 21/23
  transplants successfully engrafted
• Barker, NJ et al. Transplantation of two
  partially HLA-matched UCB units to enhance
  engraftment in adults with hematologic
  malignancy, Blood.2005105-1343-1347

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CORD BLOOD

• May be useful in Tissue Engineering (TE), a
  process controlling cell behavior to allow their
  implantation along with non-biologic scaffolds,
  in place of traditional synthetic prostheses, to
  repair and reconstruct tissue
• Examples Blood Vessels, Heart Valves, Muscle,
  Cornea

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CORD BLOOD

• Tissue Engineered Vascular Grafts
• Start with cell source of desired cell function,
  e.g. endothelial progenitor cells from bone
  marrow, blood or cord blood
• Construct cell-scaffold interaction to mimic
  natural environment, i.e. pulsatile blood flow
  and pressure
• Still 5-10 years from FDA approval
• Vascular Medicine 2002 7241-246
• TE Pulmonary Artery, Shinoka T, NEJM
  2001344532-3

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CORD BLOOD

• Stem Cell Transplantation in Myocardial
  Infarction (MI)
• Lee MS et al, Ann Int Med 2004 140729-37
• Staurer BE, et al. Circulation 20021061913-8
• Intracoronary transplantation of autologous,
  mononuclear bone marrow cells subsequent to an
  acute anterior MI showed improved myocardial
  perfusion
• Maybe cord blood could be a source for allogeneic
  repair research?

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CORD BLOOD

• Cord Blood Stem Cell Act of 2005 Introduced in
  Congress
• Tremendous potential to save lives

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Patricia Lang, MS, MT(ASCP)Director of Marrow
Donor ProgramRhode Island Blood Center
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Stem Cell Therapeutic Research Act of 2005

• Sen. Jack Reed one of key sponsors
• Reauthorizes National Marrow Donor Program with
  expanded scope

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Stem Cell Therapeutic Research Act of 2005
structure funding
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Stem CellSources Therapeutic Use

• Bone marrow
• Peripheral Blood
• Umbilical Cord Blood
• Treatment for 60 diseases (cancerous
  genetic)

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Challenges to Transplantation

• Matched stem cells needed
• Fewer minority patients have matches
• 45 of African-Americans find matched donors
  compared to
• 90 of caucasians

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Solutions

• Caucasians without matched adult donor can use
  double cord blood units
• Cord blood can close minority gap

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Cord Blood Banks (CBB)

• 20 NMDP public CBB
• 56,000 cords listed
• 60 cords distributed / month
• 15 of total NMDP transplants increasing
• 1 satellite in Worcester, MA
• Dana Farber soon to open
• 6 non-NMDP public CBB
• 15-20 private CBB

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Reimbursement for Cord Blood Unit(CBU)

• Transplant Center requests CBU from NMDP Cord
  Blood Bank (CBB)
• NMDP requests pays CBB
  (15,500 - 26,000)
• Transplant Center charges patient / insurance
  company for CBU

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State Legislation to

• Create public cord blood banks (NJ, TX,
  VA, CT, GA)
• Support stem cell research (NJ, CT,
  CA, VA, GA)
• Increase awareness of donation option (NJ, NM,
  WI, GA, IL)

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GA Senate Bill 148

• Creates CBB or network of banks
• Requires informing pregnant women of opportunity
  to donate
• Passed 1 committee but may get stuck in Rules
  Committee due to controversy over embryonic cells

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CT Legislation

• 4/06 Public Act 06-77 created commission
  to study report on CBB
• House Bill 7158 Senate Bill 311 proposed 1/07
  will fund CBB
• Cords will be provided to CT researchers at no
  charge

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NJ Legislation

• Publicly funded CBB
• 300,000 for education outreach
• 150 million to build research center
• 2 processing storage facilities
• Cords provided free to NJ researchers

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State Legislative Activity Increasing(2/2/07 AP
article by Vinnee Tong)

• 10 states have passed laws related to cord blood
  donation banking
• 12 states are expected to consider legislation in
  2007

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Public Cord Blood Banks

• Satisfy public desire to donate
• Provide cord blood for transplantation
• Give minority patients more options
• Provide cord blood for research

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Rhode Island Blood Center
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Rhode Island Blood Center

• 501c(3) not for profit
• Board of Trustees
• 11 hospital CEOs or designees
• 11 community representatives

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RIBC, by the numbers

• 5 Donor Centers
• 1,470 blood drives / year
• 100,000 blood donations
• 240,000 products manufactured
• 5 testing laboratories in Providence
• 1.3 million tests
• 365 employees

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RIBC Industry Leader

• Blood Collections
• National average 55/1000 pop.
• RIBC 95/1000 pop.
• 25 from automated technology
• Exceptional donor satisfaction

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RIBC Industry Leader

• Blood product manufacturing
• 100 leukoreduction, RBCs and platelets
• 100 bacterial testing of platelets
• HLA Antibody screening to minimize TRALI

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RIBC Industry Leader

• Laboratory Services on site
• Infectious disease testing Lab
• Nucleic Acid Amplification Lab (NAT)
• Human Leukocyte Antigen Lab (HLA)
• Red Cell Reference Lab
• DNA Lab

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RIBC Testing Capabilities

• Infectious Disease Testing
• High throughput automated testing platforms
• Hepatitis B Surface Antigen
• Hepatitis B Core Antibody
• HIV 1/2 Antibody
• Hepatitis C Antibody
• HTLV 1/2
• CMV Antibody
• Syphilis
• Nucleic Acid Amplification Testing
• HIV / HCV
• WNV
• Blood typing , ABO, Rh,

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Licensure and Accreditation

• FDA 878
• RI 150
• AABB member 936
• CLIA 41D0670559
• ASHI 01-1-RI-01-1
• NMDP

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Accreditations

• American Society for Histocompatibility and
  Immunogenetics (ASHI)
• Accredited Human Leukocyte Antigen (HLA) Lab
• Testing
• Serology Typing Class I
• DNA Typing Class I Low resolution SSP
• DNA Typing Class II Low resolution and High
  resolution SSP
• Antibody Screening/Identification Class I and
  II, CDC, microarray
• Crossmatching T cells- CDC, AHG
• B cells- CDC
• Luminex HLA antibody screening

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AABB Accreditation

• Blood Collection Activities
• Hematopoietic Progenitor Cell (HPC) collections
• Parentage Testing
• Reference Laboratory

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ASHI Accreditation

• HSC/BM Transplantation Related Donor
• Solid Organ Transplantation Live Donor
• Transfusion Support
• Histocompatibility testing for other clinical
  purposes.

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Other Programs

• Rhode Island Marrow Donor Program (MDP)
• 37,000 registered donors with 29 peripheral blood
  stem cell procedures performed by Rhode Island
  Blood Center staff in Fiscal Year 2006.
• The Rhode Island Blood Center MDP, is rated a
  "high performing" center in quality assurance
  indicators as measured against national standards
  by NMDP.

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Recent Research Collaborations

• HPV Vaccine
• Associate Investigator in phase I study of
  immunization with altering HPV E7 lipopeptide
  epitope vaccine and dendritic cells presenting
  the E7 epitope for the treatment of recurrent or
  persistent cervical cancer (NCI T98-0072)
• Dendritic Cell Research Collection
• NMDP-PBSC protocol

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RIBC Regional Cord Blood Program- Advantages

• In region location and management
• Use existing infrastructure
• Accelerate startup time
• Achieve greater diversity
• Committed product inventory
• research
• transplant

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RIBCs Interest in Cord Blood

• Future of transplant medicine
• Support research
• Consistent with Mission/Vision

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RIBC can offer

• Established relationship with hospitals
• Donor recruitment/ PR expertise
• Product collection standardization
• Training
• SOPs
• Medical/Technical/Testing expertise
• Complete
• In house

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RIBC can offer

• Processing / Inventory management
• On site
• cGMP environment
• Regional distribution
• Established systems
• 24/7
• Customer Service and Support
• Research and transplant

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Financial/Operational Estimates

• To Establish Viable Public Cord Blood Bank
• 10 million over 5 years
• Self sustaining gt 5years

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RIBC cannot offer

• Start up funding
• Ongoing financial subsidy
• Guarantee of financial success

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Challenges for the Commission

• Secure 5 year funding
• Private , foundations, corporations etc..
• Public , already strained healthcare s
• Secure commitment from hospitals