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J.J. Nietfeld, Ph.D.

The cord blood dispute. J.J. Nietfeld, Ph.D. University Medical Center Department of Pathology Utrecht, The Netherlands. Controversy. Private CB banking. Public CB banking. CB is stored for family use - autologous - allogeneic (sibling). CB is donated for allogeneic use

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J.J. Nietfeld, Ph.D.

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  1. The cord blood dispute J.J. Nietfeld, Ph.D. University Medical Center Department of Pathology Utrecht, The Netherlands

  2. Controversy Private CB banking Public CB banking CB is stored for family use - autologous - allogeneic (sibling) CB is donated for allogeneic use - in an unrelated ppatient.

  3. Very low probability • Incorrect Arguments - Counterarguments • Unethical (promise, deny) • Less than 5% • Quality standards • Limitations • Leukemia • Many other diseases • Genetic disease • Acquired, Gene therapy • No GVH effect • More ‘auto’ than ‘allo’ • No adults (cell number) • Big / Double CB, Expansion • No long storage • Cryobiology, Veterinary • BM / PBSC later available • Ageing, disease

  4. Cord blood use For ~ 20 years articles have been published, claiming that the probability of autologous CB use is almost non-existent or very low. Most of these articles were based on unsubstantiated or even “invented” data.

  5. “Invented” data AAP ‘07: Likelihood of autologous CB transplant is 1:1000 to < 1:200000 Reference: Johnson ’97 Johnson ’97: Likelihood of autologous CB transplant till age 21 is 1:2700

  6. EGE ’04 RCOG ’06 WMDA ’06 AAP ’07 AMA ’07 ACOG ’08 ASBMT ’08 Eurocord ‘08 Probability of autologous CB use: 1:1000 – 1:200000 Probability in opinions/statements

  7. Data Sources 14 references • Johnson ‘97 1:2700 auto, 21 yrs. • Annas ‘99 1:20000 auto + allo, 20 yrs. • Kline ‘01 1:10000 & 1:200000 (NYBC, NHLBI) void unsubstantiated

  8. New data Nietfeld, JJ et al. Lifetime probabilities of hematopoietic stem cell transplantation in the U.S. BBMT 2008; 14: 316-322. NEW ! Nietfeld, JJ et al. On the probability of using cord blood. BBMT 2008; 14: 724-725.

  9. Data sources • Annual transplants (CIBMTR). • Annual diagnoses (SEER). • Demographic data (US Census).

  10. 4 HSCT Scenario’s • Autologous transplant. • Allogeneic transplant. • Autologous or allogeneic transplant. • Upper limit.

  11. Auto 1:400 Auto or allo 1:200 Upper limit 1:100 BBMT paper Johnson (auto, 21 yrs.) 1:2700 Lowest probability 1:200000 Opinions Probability comparison

  12. Transplant percentages EBMT report 2007, data from 613 centers Allo Auto Total Leukemias 7153 908 8061 28% 61% Total 10072 15491 25563

  13. Long term CB storage CB quality maintained after 15 yrs. cryogenic storage. (Broxmeyer, H. E. et al. PNAS 2003; 100; 645–650) Cryogenic temp. -196 °C (liquid N2) Vitrification -135 °C (no biochemistry) Entropy threshold -160°C (no chemistry) Cosmic radiation + background radiation cause only significant damage after 2000 years.

  14. Old opinions sustained Sullivan, MJ Banking on cord blood stem cells Nature Reviews Cancer 2008; 8: 555–563. 16 references against private CB banking ! Numerous flaws / errors.

  15. Lack of up to date information • Pediatrics, 2009;123;1011-17. Thornley et al. • - Transplanters do not endorse private CB banking • - Data are from 2004 • AAP NEWS, April 2009 • Only 18-19% of pediatricians indicate to have sufficient knowledge on cord blood banking.

  16. Auto CB storage not cost-effective? • Kaimal et al. O&G, Oct. 2009 • ‘Additional costs’ of $ 3,620 for 20 years storage • Probability to need an auto TX in 20 years is 0.04% • 0.0026 life-year gained, means $ 1,374,246 /life-year Remarks • Life-year is NOT a year of life expectancy • Lifetime probability to receive an auto TX is 0.23% • Costs: PBSC/BM = $ 10,000, allo CB unit > $ 30,000

  17. Present cord blood situation • Stored CB: ~ 1,500,000 U* • public: ~ 500,000 U* • family (private) ~ 1,000,000 U* • Used CB: > 15,000 U* • public ~ 15,000 U* • family (private) > 200 U* * U = units

  18. CB use for autologous transplantation > 200 auto CB transplants in 1998-2009 73% in 2008-2009 89% regenerative medicine 60% cerebral palsy 16% other brain disorders 11% type-1 diabetes 2% other PGCB

  19. = Allogeneic Cord Blood = Autologous Cord Blood = exponential growth = linear growth Autologous and allogeneic CB use (cumulative) NMDP PGCB

  20. More CB stem cell possibilities • Hematopoietic stem cells (HSC) • Mesenchymal stem cells • C. MAPC’s (Multipotent Adult Progenitor Cells) • USCC’s (Unrestricted Somatic Stem Cells)

  21. Applications • Established: HSCT B. Experimental: Neurological Diabetes Heart / heart valves C. Future: Bone / cartilage repair Tumor immunotherapy Blood transfusion (fetal Hb) Radiation damage HIV / AIDS

  22. Conclusions Negative opinions on private (family) cord blood banking are based on: • Void / unsubstantiated data • Outdated data • Ignoring literature • Misconceptions

  23. Goals Revision of outdated opinions. Disappearance of the controversy. • Public and private CB banks both have a function. • Ideally, a CB bank would collect for: private use + public use + research. 3. Clearer choices for expecting parents.

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