J.J. Nietfeld, Ph.D.
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Transcript of J.J. Nietfeld, Ph.D.
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J.J. Nietfeld, Ph.D.
University Medical Center
Department of Pathology
Utrecht, The Netherlands
The cord blood dispute
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Controversy
Public CB bankingPrivate CB banking
CB is donated for allogeneic use
- in an unrelated ppatient.
CB is stored for family use
- autologous
- allogeneic (sibling)
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Arguments
• Unethical (promise, deny) – Less than 5%
- Counterarguments
– Incorrect
• Quality standards
• Leukemia
• Genetic disease
• No GVH effect
• No adults (cell number)
• No long storage
• BM / PBSC later available
• Very low probability
– Limitations
– Many other diseases
– Acquired, Gene therapy
– More ‘auto’ than ‘allo’
– Big / Double CB, Expansion
– Cryobiology, Veterinary
– Ageing, disease
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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.
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“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
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Probability in opinions/statements
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
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Data Sources
– Johnson ‘97 1:2700 auto, 21 yrs.
– Annas ‘99 1:20000 auto + allo, 20 yrs.
– Kline ‘01 1:10000 & 1:200000 (NYBC, NHLBI)
14 references
void
unsubstantiated
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New data
Nietfeld, JJ et al.
Lifetime probabilities of hematopoietic stem cell transplantation in the U.S.
BBMT 2008; 14: 316-322.
Nietfeld, JJ et al.
On the probability of using cord blood.
BBMT 2008; 14: 724-725.
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Data sources
1. Annual transplants (CIBMTR).
2. Annual diagnoses (SEER).
3. Demographic data (US Census).
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4 HSCT Scenario’s
1. Autologous transplant.
2. Allogeneic transplant.
3. Autologous or allogeneic transplant.
4. Upper limit.
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Lifetime HSCT probabilities
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
10 20 30 40 50 60 70
Age (years)
Cu
mu
lati
ve
Pro
ba
bili
ty (
%)
auto allo auto/allo limit
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Probability comparison
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
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Leukemias
Transplant percentages
Allo Auto Total
10072 15491 25563
7153 908 8061
Total
28%
EBMT report 2007, data from 613 centers
61%
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Long term CB storage
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.
CB quality maintained after 15 yrs. cryogenic storage.
(Broxmeyer, H. E. et al. PNAS 2003; 100; 645–650)
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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.
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• AAP NEWS, April 2009
Only 18-19% of pediatricians indicate to have sufficient knowledge on cord blood banking.
• Pediatrics, 2009;123;1011-17. Thornley et al.
- Transplanters do not endorse private CB banking
- Data are from 2004
Lack of up to date information
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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
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
Remarks
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Cord blood procurement costs(development at 3% inflation)
0
50
100
150
200
250
0 10 20 30 40 50 60 70
Time (years)
€ (t
ho
usa
nd
s). Public CB
Family CB
PBSC's
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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
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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
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04080120160200240280320
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Year
Au
to C
B u
nits.
Autologous and allogeneic CB use (cumulative)
0500
1000150020002500300035004000
Allo
CB
un
its.
= linear growth = exponential growth= Allogeneic Cord Blood = Autologous Cord Blood
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More CB stem cell possibilities
A. Hematopoietic stem cells (HSC)
B. Mesenchymal stem cells
C. MAPC’s (Multipotent Adult Progenitor Cells)
D. USCC’s (Unrestricted Somatic Stem Cells)
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Applications
A. Established: HSCT
B. Experimental:
C. Future:
Neurological
Diabetes
Heart / heart valves
Bone / cartilage repair
Tumor immunotherapy
Blood transfusion (fetal Hb)
Radiation damage
HIV / AIDS
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Conclusions
Negative opinions on
private (family) cord blood banking
are based on:
• Void / unsubstantiated data
• Outdated data
• Ignoring literature
• Misconceptions
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1. Revision of outdated opinions.
2. Disappearance of the controversy.
Goals
• 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.