J.J. Nietfeld, Ph.D.
-
Upload
azalia-lawrence -
Category
Documents
-
view
45 -
download
1
description
Transcript of J.J. Nietfeld, Ph.D.
1
J.J. Nietfeld, Ph.D.
University Medical Center
Department of Pathology
Utrecht, The Netherlands
The cord blood dispute
2
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)
3
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
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
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
7
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
8
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.
9
Data sources
1. Annual transplants (CIBMTR).
2. Annual diagnoses (SEER).
3. Demographic data (US Census).
10
4 HSCT Scenario’s
1. Autologous transplant.
2. Allogeneic transplant.
3. Autologous or allogeneic transplant.
4. Upper limit.
11
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
12
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
13
Leukemias
Transplant percentages
Allo Auto Total
10072 15491 25563
7153 908 8061
Total
28%
EBMT report 2007, data from 613 centers
61%
14
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)
15
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.
16
• 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
17
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
18
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
19
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
20
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
21
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
22
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)
23
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
24
Conclusions
Negative opinions on
private (family) cord blood banking
are based on:
• Void / unsubstantiated data
• Outdated data
• Ignoring literature
• Misconceptions
25
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.