- Email: [email protected]
Ethics of cord blood banking
Current Obstetrics & Gynaecology (2002) 12, 175^177
c 2002 Elsevier Science Ltd doi:10.1054/cuog.2001.0255 available online at http://www.idealibrary.com on
Ethics of cord blood banking Ruth Warwick and Deirdre Fehily London Cord Blood Bank, North London Blood Centre, Colindale Avenue, London NW9 5BG, UK
KEYWORDS cord blood; stem cells; cord blood banking
Summary Cord blood can be used instead of bone marrow for transplantation to reconstitute the haemopoietic and immune systems. Additional claims have been made by commercial cord blood banks for the use of cord blood as a treatment for a variety of other conditions thatcurrently have little practical foundation.Thisis one of a number of ethical issues relating to cord blood banking that requires consideration.There is a need to assess whether non-haemopoietic stem cells are present in cord blood in su⁄cient quantity to make them a useful source for tissue or organ ‘engineering’.
c 2002 Elsevier Science Ltd
INTRODUCTION Prior to its ¢rst use in 1989 for transplantation, cord blood (CB) was discarded. The demonstration that haemopoietic and immunological reconstitution was possible using CB instead of bone marrow led to the establishment of unrelated CB banking. Over 65 000 unrelated CB units have been banked and over 1500 of these units have been used for the equivalent of bone marrow transplantation. CB is mostly used if a matching bone marrow donor cannot be found. Some centres use a half-matched parent as an alternative to CB. There are numerous ethical issues that arise from the banking and transplantation of CB, which have been discussed widely in the literature. Some of the issues are discussed here.
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Recipients could try to trace their matched donor for additional donations, e.g. for immuno-therapy or as an extreme example, as a matching kidney donor. Donors could be informed of newly discovered genetic disease susceptibility information of relevance to their own health. It has not yet been tested whether the mother, infant or the CB bank owns CB. With linkage, ownership might be easier to establish although tracking could also be undertaken using molecular tissue typing or ¢ngerprinting techniques. Banks could recall, or re-sample and re-test the donor for newly recognized infectious agents, to check for previously unrecognized genetic abnormalities or for look-back exercises if the recipient developed a transmissible disease.
ETHNIC TARGETING CB can be collected from donors in those ethnic groups that are not adequately represented in bone marrow donor panels. The London CB Bank has collected 40% of 5000 units of CB from these groups. This helps address reduced access to transplant health care for these minorities and is an example of positive discrimination. Some might criticize this as disadvantaging the majority.
CONSENT ISSUES There are numerous issues in this area relating to ensuring that consent for altruistic donation is genuine and informed. PRACTICE POINTS K
OWNERSHIP OF CB There are concerns relating to patents, ownership, con¢dentiality and privacy. For example, maintaining linkage between donor and donation may result in a number of consequences:
Correspondence to: RW. Address as above. Fax: +44 (0)208 732 5404; E-mail: [email protected].
K
Optimal time for procedures: When is it best to ethically harvest CB or to seek consent? For example, is the mother able to give genuine consent if she is approached during labour or under the e¡ect of recent analgesia? Collection of CB: This must not compromise care of the donor or other patients in the delivery suite; there must be no con£ict of interest between the CB collection and clamping of the umbilical cord. Collection techniques that interfere with the
176
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CURRENT OBSTETRICS & GYNAECOLOGY
normal care given to the mother and infant or to their privacy can compromise ethical standards of care. For example, if altruistic collection is undertaken with the placenta in utero, then the mother might feel coerced to give her consent for collection for fear of alienating healthcare professionals. Some banks obtain written consent for donation once a successful collection has been made albeit with plentiful information given in the antenatal period. This approach is di⁄cult to justify if the collection is obtained with the placenta in utero Maternal consent: This is required for all uses of CB and procedures. For example, the mother must give consent for testing, including for HIV and to be informed of test results relevant to her health and the health of the infant donor; should include provision of medical and behavioural histories and post-donation information from the mother and obtain information from other relevant sources Units unsuitable for transplantation: If these are to be supplied for research, especially for commercial purposes and for cell lines, then speci¢c detailed consent should be obtained
Families who have read persuasive promotional information from commercial banks are now approaching many obstetric and midwifery sta¡ in the UK. Many obstetric patients know that CB can be banked for autologous or family use on the remote chance that a family member might require a haemopoietic transplant in the future. However, autologous CB may not be the ideal source of stem cells for a variety of conditions such as leukaemia. This is because the may have diseased cells in it or have the same genetic predisposition to the disease that requires transplantation. Unrelated CB banking relies on the well-established ethos of altruism. The establishment of commercial CB banks, for family use only, challenges this principle. Autologous CB banking has a commercial if not a current scienti¢c application and CB banking has been the subject of patent applications in the US and Europe. Mesenchymal stem cells have been demonstrated to be present, albeit in very small numbers, in CB and have been shown to be capable of di¡erentiation into chondrocytes, adiposites and osteocytes.However, the translation from demonstrating the presence of stem cells in CB, into a useful therapy remains to be achieved. PRACTICE POINTS K
DIRECTED CB COLLECTION FOR HIGH-RISK FAMILIES Some CB banks provide a service to clinicians for highrisk families. This is most usual where an existing child has acute lymphoblastic leukaemia or a genetic disorder of the bone marrow or immune system. Even in these families, few of the banked units are transplanted, but they can provide a life-saving resource. Any matching sibling CB donor will also be a match for marrow. At the London CB bank where over 90 directed units have been collected only ¢ve have been transplanted since 1996. More will probably be used in time, but childhood leukaemia is mostly treated with chemotherapy and only a minority with bone marrow transplantation. For those cases where there is a very low chance of the donation ever being used, it could be argued that the resources allocated to the provision of this service could be better utilized for other aspects of patient care. The question of the cost of long-term storage and the funding provision for directed services are not fully resolved.
K
K
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Commercial donations have rarely been used despite large numbers being banked; commercial banking may threaten the availability of matches which would only be available from donors who could not a¡ord to bank for their own use Persuasive commercial marketing techniques are used when mothers are emotionally vulnerable but are di⁄cult to justify scienti¢cally Indications for conditions amenable to stem cell therapy may be claimed by commercial banks but for which CB has not yet been used Commercial CB banking within the National Health Service: There may be potential legal liability carried by NHS sta¡ supporting or assisting in CB collection on behalf of a commercial bank. Also, objective assurance that commercial banks have appropriate standards of safety and quality is needed. The Royal College of Obstetricians has provided guidance for NHS Trusts in this area Altruistic donors need to be aware that commercial banking is available if they are to give genuine consent for CB collection to a public bank
COMMERCIAL CB BANKING Commercial cord banking originated in the United States and the ethical issues associated with this have been well documented. However, these have not been considered in the UK before now, because commercial banks have only started to show an interest in the UKvery recently.
CONCLUSION The ethics of CB banking have been debated since the 1990s and dialogue in this area will continue as long as biotechnology provides new therapeutic options.
ETHICS OF CORD BLOOD BANKING
RESEARCH DIRECTIONS K
K
Compare transplant outcomes between matching CB and parental single haplotype-matched (halfmatched) bone marrow or peripheral blood stem cells Investigate whether CB is a feasible source of nonhaemopoietic stem cells for tissue engineering
FURTHER READING Burgio GR, Locatelli F. Transplant of bone marrow and cord blood hematopoietic stem cells in pediatric practice, revisited according to the fundamental principles of bioethics. Bone Marrow Transplantation 1997; 19:1163^1168. Campagnoli vCJD, Roberts AGI, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identi¢cation of mesenchymal stem/progenitor cells in hu-
177
man ¢rst trimester fetal blood, liver and bone marrow. Blood 2001; 98: 2396^2402. Cohen SBA, Gluckman E, Rubinstein P, Madrigal JA, (eds). Cord Blood Characteristics: Role in Stem Cell Transplantation. London, UK: M. Dunitz, 2000. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 2000; 1: 235^242. Gluckman E. Hematopoietic stem-cell transplants using umbilical-cord blood. N Engl J Med 2001; 24: 1860 ^1861. Haley R, Harvath L, Sugarman J. Ethical issues in cord blood banking: summary of a workshop.Transfusion 1998; 38: 867^ 873. Lind SE. Ethical considerations related to the collection and distribution of cord blood stem cells for transplantation to reconstitute hematopoietic function.Transfusion1994; 9: 828 ^ 834 Royal College of Obstetricians and Gynaecologists: Scienti¢c Advisory Committee Opinion Paper, 2 October 2001. Sugarman J, Reisner EG, Kurtzberg J. Ethical aspects of banking placental blood for transplantation. JAMA1995; 274: 1783^1785. Titmus R. The Gift Relationship: From Blood to Social Policy. London; Allen and Unwin,1971.
c 2002 Elsevier Science Ltd doi:10.1054/cuog.2001.0255 available online at http://www.idealibrary.com on
Ethics of cord blood banking Ruth Warwick and Deirdre Fehily London Cord Blood Bank, North London Blood Centre, Colindale Avenue, London NW9 5BG, UK
KEYWORDS cord blood; stem cells; cord blood banking
Summary Cord blood can be used instead of bone marrow for transplantation to reconstitute the haemopoietic and immune systems. Additional claims have been made by commercial cord blood banks for the use of cord blood as a treatment for a variety of other conditions thatcurrently have little practical foundation.Thisis one of a number of ethical issues relating to cord blood banking that requires consideration.There is a need to assess whether non-haemopoietic stem cells are present in cord blood in su⁄cient quantity to make them a useful source for tissue or organ ‘engineering’.
c 2002 Elsevier Science Ltd
INTRODUCTION Prior to its ¢rst use in 1989 for transplantation, cord blood (CB) was discarded. The demonstration that haemopoietic and immunological reconstitution was possible using CB instead of bone marrow led to the establishment of unrelated CB banking. Over 65 000 unrelated CB units have been banked and over 1500 of these units have been used for the equivalent of bone marrow transplantation. CB is mostly used if a matching bone marrow donor cannot be found. Some centres use a half-matched parent as an alternative to CB. There are numerous ethical issues that arise from the banking and transplantation of CB, which have been discussed widely in the literature. Some of the issues are discussed here.
K
K
K
K
Recipients could try to trace their matched donor for additional donations, e.g. for immuno-therapy or as an extreme example, as a matching kidney donor. Donors could be informed of newly discovered genetic disease susceptibility information of relevance to their own health. It has not yet been tested whether the mother, infant or the CB bank owns CB. With linkage, ownership might be easier to establish although tracking could also be undertaken using molecular tissue typing or ¢ngerprinting techniques. Banks could recall, or re-sample and re-test the donor for newly recognized infectious agents, to check for previously unrecognized genetic abnormalities or for look-back exercises if the recipient developed a transmissible disease.
ETHNIC TARGETING CB can be collected from donors in those ethnic groups that are not adequately represented in bone marrow donor panels. The London CB Bank has collected 40% of 5000 units of CB from these groups. This helps address reduced access to transplant health care for these minorities and is an example of positive discrimination. Some might criticize this as disadvantaging the majority.
CONSENT ISSUES There are numerous issues in this area relating to ensuring that consent for altruistic donation is genuine and informed. PRACTICE POINTS K
OWNERSHIP OF CB There are concerns relating to patents, ownership, con¢dentiality and privacy. For example, maintaining linkage between donor and donation may result in a number of consequences:
Correspondence to: RW. Address as above. Fax: +44 (0)208 732 5404; E-mail: [email protected].
K
Optimal time for procedures: When is it best to ethically harvest CB or to seek consent? For example, is the mother able to give genuine consent if she is approached during labour or under the e¡ect of recent analgesia? Collection of CB: This must not compromise care of the donor or other patients in the delivery suite; there must be no con£ict of interest between the CB collection and clamping of the umbilical cord. Collection techniques that interfere with the
176
K
K
CURRENT OBSTETRICS & GYNAECOLOGY
normal care given to the mother and infant or to their privacy can compromise ethical standards of care. For example, if altruistic collection is undertaken with the placenta in utero, then the mother might feel coerced to give her consent for collection for fear of alienating healthcare professionals. Some banks obtain written consent for donation once a successful collection has been made albeit with plentiful information given in the antenatal period. This approach is di⁄cult to justify if the collection is obtained with the placenta in utero Maternal consent: This is required for all uses of CB and procedures. For example, the mother must give consent for testing, including for HIV and to be informed of test results relevant to her health and the health of the infant donor; should include provision of medical and behavioural histories and post-donation information from the mother and obtain information from other relevant sources Units unsuitable for transplantation: If these are to be supplied for research, especially for commercial purposes and for cell lines, then speci¢c detailed consent should be obtained
Families who have read persuasive promotional information from commercial banks are now approaching many obstetric and midwifery sta¡ in the UK. Many obstetric patients know that CB can be banked for autologous or family use on the remote chance that a family member might require a haemopoietic transplant in the future. However, autologous CB may not be the ideal source of stem cells for a variety of conditions such as leukaemia. This is because the may have diseased cells in it or have the same genetic predisposition to the disease that requires transplantation. Unrelated CB banking relies on the well-established ethos of altruism. The establishment of commercial CB banks, for family use only, challenges this principle. Autologous CB banking has a commercial if not a current scienti¢c application and CB banking has been the subject of patent applications in the US and Europe. Mesenchymal stem cells have been demonstrated to be present, albeit in very small numbers, in CB and have been shown to be capable of di¡erentiation into chondrocytes, adiposites and osteocytes.However, the translation from demonstrating the presence of stem cells in CB, into a useful therapy remains to be achieved. PRACTICE POINTS K
DIRECTED CB COLLECTION FOR HIGH-RISK FAMILIES Some CB banks provide a service to clinicians for highrisk families. This is most usual where an existing child has acute lymphoblastic leukaemia or a genetic disorder of the bone marrow or immune system. Even in these families, few of the banked units are transplanted, but they can provide a life-saving resource. Any matching sibling CB donor will also be a match for marrow. At the London CB bank where over 90 directed units have been collected only ¢ve have been transplanted since 1996. More will probably be used in time, but childhood leukaemia is mostly treated with chemotherapy and only a minority with bone marrow transplantation. For those cases where there is a very low chance of the donation ever being used, it could be argued that the resources allocated to the provision of this service could be better utilized for other aspects of patient care. The question of the cost of long-term storage and the funding provision for directed services are not fully resolved.
K
K
K
K
Commercial donations have rarely been used despite large numbers being banked; commercial banking may threaten the availability of matches which would only be available from donors who could not a¡ord to bank for their own use Persuasive commercial marketing techniques are used when mothers are emotionally vulnerable but are di⁄cult to justify scienti¢cally Indications for conditions amenable to stem cell therapy may be claimed by commercial banks but for which CB has not yet been used Commercial CB banking within the National Health Service: There may be potential legal liability carried by NHS sta¡ supporting or assisting in CB collection on behalf of a commercial bank. Also, objective assurance that commercial banks have appropriate standards of safety and quality is needed. The Royal College of Obstetricians has provided guidance for NHS Trusts in this area Altruistic donors need to be aware that commercial banking is available if they are to give genuine consent for CB collection to a public bank
COMMERCIAL CB BANKING Commercial cord banking originated in the United States and the ethical issues associated with this have been well documented. However, these have not been considered in the UK before now, because commercial banks have only started to show an interest in the UKvery recently.
CONCLUSION The ethics of CB banking have been debated since the 1990s and dialogue in this area will continue as long as biotechnology provides new therapeutic options.
ETHICS OF CORD BLOOD BANKING
RESEARCH DIRECTIONS K
K
Compare transplant outcomes between matching CB and parental single haplotype-matched (halfmatched) bone marrow or peripheral blood stem cells Investigate whether CB is a feasible source of nonhaemopoietic stem cells for tissue engineering
FURTHER READING Burgio GR, Locatelli F. Transplant of bone marrow and cord blood hematopoietic stem cells in pediatric practice, revisited according to the fundamental principles of bioethics. Bone Marrow Transplantation 1997; 19:1163^1168. Campagnoli vCJD, Roberts AGI, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identi¢cation of mesenchymal stem/progenitor cells in hu-
177
man ¢rst trimester fetal blood, liver and bone marrow. Blood 2001; 98: 2396^2402. Cohen SBA, Gluckman E, Rubinstein P, Madrigal JA, (eds). Cord Blood Characteristics: Role in Stem Cell Transplantation. London, UK: M. Dunitz, 2000. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 2000; 1: 235^242. Gluckman E. Hematopoietic stem-cell transplants using umbilical-cord blood. N Engl J Med 2001; 24: 1860 ^1861. Haley R, Harvath L, Sugarman J. Ethical issues in cord blood banking: summary of a workshop.Transfusion 1998; 38: 867^ 873. Lind SE. Ethical considerations related to the collection and distribution of cord blood stem cells for transplantation to reconstitute hematopoietic function.Transfusion1994; 9: 828 ^ 834 Royal College of Obstetricians and Gynaecologists: Scienti¢c Advisory Committee Opinion Paper, 2 October 2001. Sugarman J, Reisner EG, Kurtzberg J. Ethical aspects of banking placental blood for transplantation. JAMA1995; 274: 1783^1785. Titmus R. The Gift Relationship: From Blood to Social Policy. London; Allen and Unwin,1971.