Transcript PowerPoint-presentatie

The cord blood dispute
J.J. Nietfeld, Ph.D.
University Medical Center
Department of Pathology
Utrecht, The Netherlands
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Controversy
Private CB banking
Public CB banking
CB is stored for
family use
CB is donated for
allogeneic use
- autologous
- in an unrelated
ppatient.
- allogeneic (sibling)
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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
• Very low probability
– Incorrect
3
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
Probability of
autologous CB use:
1:1000 – 1:200000
ACOG ’08
ASBMT ’08
Eurocord ‘08
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Data Sources
14 references
– Johnson ‘97
1:2700 auto, 21 yrs.
– Annas ‘99
1:20000
– Kline ‘01
1:10000 & 1:200000 (NYBC, NHLBI)
auto + allo, 20 yrs. 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
Cumulative Probability (%)
auto
allo
auto/allo
limit
1
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
10
20
30
40
50
Age (years)
60
70
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Probability comparison
BBMT paper
Auto
1:400
Auto or allo
1:200
Upper limit
1:100
Johnson (auto, 21 yrs.)
1:2700
Opinions
Lowest probability
1:200000
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Transplant percentages
EBMT report 2007, data from 613 centers
Leukemias
Total
Allo Auto Total
7153 908 8061
28%
61%
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10072 15491 25563
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.
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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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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.
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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
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
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Cord blood procurement costs
(development at 3% inflation)
€ (thousands).
250
200
Public CB
150
Family CB
PBSC's
100
50
0
0
10
20
30
40
50
60
70
Time (years)
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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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2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
320
280
240
200
160
120
80
40
0
Auto CB units.
4000
3500
3000
2500
2000
1500
1000
500
0
1998
Allo CB units.
Autologous and allogeneic CB use
(cumulative)
Year
= Allogeneic Cord Blood
= linear growth
= Autologous Cord Blood
= exponential growth
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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:
Neurological
Diabetes
Heart / heart valves
C. Future:
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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Goals
1. Revision of outdated opinions.
2. 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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