Lecture, leuven; november 2013

Cord Blood Banks between Therapy and Research: Ownership, Informed Consent and Solidarity

Elena Salvaterra, [email protected]

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Aims

• Give a picture of cord blood and cord blood banks

• Identify ethical principles and issues related to cord blood banks

• Look at the interaction of science, technique and ethics in cord blood banking

• Discuss the ELSI of cord blood banks

Erasmus Mundus Students -Leuven 2013

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Cord Blood….Banks


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… From the Newborn Cord Blood …


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… To Cord Blood Banks…


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Preliminary Questions

• Why is newborn cord blood important?

• Why should we collect and store it?

• How is the newborn cord blood linked to cord blood banks?


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… Newborn Cord Blood from Waste Material ..

In the past, newborn cord blood was usually destined to incinerators


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…to Source for Transplantations and Research…

• Since the 1988, CB life completely changed

• Proven standardised treatment for a number of diseases and pretious source of stem cells suitable for research


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Newborn Cord Blood History (1)

• The first CB transplant was performed in a 5-year old child with Fanconi Anemia (1988)

• It was a related CBT using the CB stem cells derived from the UC of the child sister


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Newborn Cord Blood History (2)

• In 1991, the first public cord blood bank was established at the New York Blood Center

• In 1993 the first allogenic unrelated CB transplant performed in a 4-year old child with laukaemia

• Since then, cord blood (CB) has been recognised standard practice treatment option in pediatric allogenic transplantation and a promising treatment in adults


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Cord Blood Characteristics and Uses (1)

• Like Bone Marrow (BM) and Perhiperhal Blood (PB), cord blood is rich of stem cells

• Stem Cells: «undifferentiated blank cells» (Fossett, 2009) able to produce either cells like themselves (self-renewal) or cells of one or several specific differentiated types


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• CB is rich of hematopoietic stem cells that can be used for the treatment of hereditary and/or haematological conditions, both malignant and non-malignant such as:– Laukaemia– Lymphoma– Myeloma– Selected Solid Tumours (e.g., retinoblastoma)

• Hematopoietic Stem Cells: Blood Forming


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• CB is rich of non hematopoietic stem cells whose potential is associated with future tissue repair and regeneration (neural, cardiac, epithelial, hepatocytic, and dermal tissue)

• Non hematopoietic stem cells: include mesenchymal stem/stromal cells (MSC), endothelial progenitor cells (EPC), and induced pluripotent stem cells (iPSC)


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Cord Blood«Ethically-Free» Stem Cell Source

• Stem cells cointained in the umbilical cord blood are adult stem cells

• Younger than stem cells included in BM and PB

• Older than stem cells derived from human embryos


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Cord Blood Advantages and Disadvantages

Compared to BMT and PBT, CBT Advantages• Absence of risks to donors (mother and newborn)• Reduced risk of transmitting infections• Greater histocompatibility/more access to patients• Immediate availability of cryopreserved cells

Disadvantages

• Longer patient recovery


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Cord Blood Banks and Transplants WorldwidePublic Vs Private (1)

• Since the first CB transplant in 1988, more

than 20,000 allogenic CB transplantations have been performed worldwide

• More than 600,000 cord blood units stored in public cord blood banks

• A number of international networks created (Netcord, Asiacord, Bone Marrow Donors Worldwide) and registries listing publicly banked CB units developed (Eurocord, Center for International Blood and Marrow Transplant Research)


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Cord Blood Banks and Transplants Worldwide Public Vs Private (2)

More than 100 public CB Banks created, mainly based in Australia, United Kingdom, USA, Belgium, Spain, Italy, France, Brasil, Israel


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• Over the last 15 years, 900,000 cord blood units have been stored in private banks for personal use

• About 100 autologous transplants have been performed worldwide

• There are about 200 private cord blood banks worldwide

(www.parentsguidecordblood.org)


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• Based on the Eurocord Registry, about 600 patients have been transplanted with allogenic related CB from 1988 to 2010 (family CB tranplants)

• Most recipients were children• Treated diseases were mostly non malignant

(e.g.,hemoglibonopathies, thalassemia)• In contrast to unrelated cord blood transplants, the

number of family CBTs has not increased year after year


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What Are Cord Blood Banks? (1)• Biobanks providing services of collection, processing,

storage and distribution of CB units for transplantation and research

• According to the origin of the collected source, CB banks fall into the broader category of pediatric biobanks

• CB banks represent a special model of pediatric biobank because of they provide CB units for clinical applications (transplants) and research

• Based on financial support, CB banks also represent a relevant model for public, private or hybrid biobanks


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What Are Cord Blood Banks? (2)

• Based on:financial supporttechnical aspectsoffered servicesunderlying values


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What Are Cord Blood Banks? (3)

• three broad categories of cord blood banks can be now identified:

Public Private Hybrid


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Public Cord Blood Banks (1)


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• Publicly funded (no fee for service)• Usually accreditated services of

collection, processing, storage, controls and distribution of CB units (AABB, Netcord, Asiacord…..)

• Structured process of information and consent


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• Dedicated to allogenic transplantation including:Related CB transplantation (sibling and relatives)Unrelated CB transplantation (all patients needed

a CBT worldwide)• Allogenic CBTs are recognised a standard practice

treatment option in pediatric allogenic transplantation, increasing in adult treatment

• Promote values as altruism, solidarity, justice →relationships of solidarity


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Private Cord Blood Banks (1)

• Fee for service (from 1000 to

2000 Euros per year + annual fee

for the storage)• CB units are stored for

autologous or family (related) use


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• Private CB banks for autologus use are not supported from clinical evidence based data

• In spite of the large number of stored CB units only three published reports of autologous CBTs

• Often they provide misleading information to parents


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• Chance that the CB stored privately will be used for autoloogus transplant is very low

• Although clinical trials are presently underway, regenerative medicine remains little more than a promising possibility and the value of CB in this field is also uncertain

• Benefits advertised from private CBBs are largely speculative


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• Private CBBs promote the private storage of the newborn CB as a «biological insurance»

• Private CBBs appeal to the sense of obligation of parents to store the newborn CB privately

• Often private CBBs sell false promises• Commercial relationship model


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• Make a distinction between: private CBBs for autologous use only

(like in Australia) or in addition to related use and

private CBBs for allogenic related (sibling or relative) transplantation (family CB banks)

and


Erasmus Mundus Students -Leuven 2013 32


• Family CBB services are clinically indicated and validated in families where the pregnant mother: has an existing child or has a known risk to have a child

affected by a disease treatable by related UC trasplantation• Family CBBs, like private CBBs in general, require

a fee for service ($ 1,500 for unit and $ 50 for storage)

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Hybrid Cord Blood Banks (1)

Fall into two broad categories:• Many offer both public and private services • So far, the only public bank offering both the

services is the Alberta Cord Blood Bank in Canada

• Other collect and store CB for private autologous or related use but make available the stored CB units to the public system, based on the choice of parents


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Other Paradigms• Turkish Model: according to the government

legislation, 25% of all privately stored CBUs is donated to the public system

• Virgin Model: 80% of the CBUs are donated to the public system and 20% is stored for private use. Profits are used to fund stem cell research


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• Spanish Model: CBUs privately stored are recorded on the Official Spanish Register of Bone Marrow Donors.

• Should a patient in need of a transplant find a matched donor, parents are obliged to donate the cord blood and the storage fee is reimbursed


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Cord Blood BanksELSI


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Cord Blood Banking and UseELSI Overview (1)

• Cord blood banking process and use raise a number of ethical, legal and social issues

Public CBBs are expression of:• Altruism• Solidarity• Cooperation• Justice as fair allocation of available CB units


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Private CBBs are expression of: • Competition• Speculation• Profit markets• Conflict with the principle of justice• Conflict with a model of social/individual trust

in science and technology


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Hybrid CBBs are expression of a combination of values underlying public and private CBBs

• Autonomy• Solidarity• Justice • Profit • “Solidarity market” Vs “Profit market”


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Cord Blood Banking and UseSpecial ELSI

• Ownership • Informed consent • Solidarity • With regard to ownership and informed

consent CBBs are a relevant model for ELSI of pediatric biobanks in general

• Solidarity is a basic principle of pediatric biobanks for research aims


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Ownership (1)

• Ownerhsip of body and body parts remains widely controversial either in common and continental legal system

• Personality Right Teory: The body and its parts are considered as corporeal components

of the personal identity Self-autonomy plays a crucial role

• Property Right Teory Body parts are considered as things which can be bought and

sold on a market place


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Ownership (2)

Within the realm of cord blood banks: • Owner of the cord blood and the cord itself is

the newborn• The mother/parents is/are legitimate to

exercise autonomy rights on behalf of the newborn until the age of the maturity


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Informed Consent General Issues (1)

• Informed consent for cord blood banking is expression of the broader issue of informed consent for pediatric biobanks

• Pediatric biobanks raise the issue to identify the subject legitimate to give the informed consent: parents/legal representative or child?

• Cord blood banks adds a third option to the model of pediatric biobanks: mother, parents or child?


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• According to the prevailing ethical and legal position, the informed consent for cord blood collection and banking should be given by the newborn mother

• The informed consent of both parents is not legally necessary


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• The child has the right to decide on the disposition of the stored cord blood (where available) once he/she becomes competent

• The age for reaching to capacity to make autonomous decisions (including informed consent) is very controversial in cord blood and broadly pediatric biobanks

• The mother informed consent principle is different from the both parents informed consent rule which is generally followed in pediatric biobanks


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Informed Consent Special Challanges (1)

The double faces of the timing• Timing of the maternal consent provision• Timing of the cord blood clamping


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• Working Group on ethical issues in umbilical cord blood banking and the American Academy of Pediatrics consider intrapartum and after-collection consent unethical

• They recommend written informed consent be obtained during prenatal care, before the onset of labor

• A confirmation of consent after delivery




…..Cord clamping timing………• Although there is no a scientific consensus on the

best time to clamping the newborn cord, it is known that clamping early allows to have the largest volume of neonatal blood, without serious effects on the newborn health (apart from pre-term infants)

• Timing of the cord clamping and risks/benefits associated with early or delayed clamping should be clarified in the informed consent process

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Informed Consent Content (1)

• Expectant mothers should be given clear and appropriate information about the options to donate cord blood for public or private or mixed use

• Expectant mothers should be informed on procedures for collecting, processing, testing, storing and using the cord blood and related risks and benefits


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• European Group on Ethics in Science and New Technologies – Opinion on “Ethical aspects of umbilical cord blood banking”, 2004

• European Recommendation Rec (2004) 8 of the Committee of Ministers on Autologous cord blood banks, 2004


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EGE Opinion“If the cord blood is to be stored by a private bank,

appropriate information should be given to the consumers (…) including the fact that the likelihood that the sample may be used to treat one’child is currently negligible, that the future therapeutic possibilities are of a very hypothetical nature and that up until now there is no indication that the present research will lead to specific therapeutic applications of one’s own cord blood cells. This information should be made clear on all media (…)”


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European Recommendation

“Where autologous cord blood banks are being established, the promotional material or information provided to families must be accurate and fully informed consent to cord blood storage must be obtained”


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• The analysis of information of the English websites of 148 private cord blood banks showed that “a pattern of confusing and potentially misleading information” were provided

• Often, private cord blood banks publish lists of disorders treatable through CB transplans without a clear distinction between diseases for whom the CBT is a proven treatment and those which could be treated in the future


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• Private cord blood banks often do not explain the difference between autologous and allogenic cord blood transplantation

• They leave expectant parents to suppose that indications for allogenic transplant also apply to autologous transplantations


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Solidarity and Justice in Cord Blood Banks (1)

• Altruism and solidarity are basic principles of cord blood banks for allogenic transplantations

• Altruism and solidarity have different applications based on their clinical use:

transplantations in sibling or relativestransplantations in unrelated patients


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• Altruism and solidarity meet the value of justice in public cord blood banks

• By making available CB units for any patient in need of stem cell CBT worldwide, public cord blood banks promote the principle of justice as fair allocation of available resources

• Respects for this principle has relevant implications for racial and ethnic minorities


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• Racial and ethnic minorities are usually underrepresented on the bone marrow registries worldwide


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• As reported in the literature, although a matched unrelated donor can be found for up to 75% of patients of Western European origin, for many ethnic groups the reverse is true with no more than 20-30% being matched

• Public CBBs contribute to overcome this problem allowing a great number of patients to benefit from a smaller pool of donors


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A Patchwork of Values (1)

• Combination of ethical values surrounding cord blood banking is not easy to understand in practice

• Public cord blood banks promote values of autonomy, solidarity and justice through allogenic CB transplantation

• They permit to a large number of patients to find an adequate donor worldwide beside the racial and ethnical differences

• They provide high quality services • They do not require a fee for service


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Patchwork of Values (2)

• Private and many hybrid cbbs support a for profit approach

• They promote services which are not based on well proven clinical data

• They provide often inaccurate and potentially misleading information to expectant parents

• They limit the access to CBT to a number of patients including racial and ethnic minorities

• They provide expensive services


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Conclusion (1)

• Which values (and consequently CBBs) should be supported?

• Should the parent choices be accepted regardless of the given information and the underlying values?

• Is better to give more chance of care to a large number of patients or to restrict them to a selected group?



Conclusion (2)

• What is critical in private cord blood banks, the false hopes they give to expectant parents or the fee for service they ask for?

• Is ethically acceptable the family cord blood bank model, asking for a fee for clinically proven services?

• Which risks are associated with a bio-market model?


Lecture, leuven; november 2013

Science

cord blood cb

cord blood units

cord blood characteristics

cord blood advantages

umbilical cord blood

cord blood banking

picture of cord blood

public cord blood banks