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

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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

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.