Ruling of the Bioethics Commission at the Federal Chancellery 19th May Report of the Bioethics Commission regarding Umbilical Cord Blood Banking

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1 BIOETHICS COMMISSION Ruling of the Bioethics Commission at the Federal Chancellery 19th May 2008 Report of the Bioethics Commission regarding Umbilical Cord Blood Banking Collecting Stem Cells from Umbilical Cord Blood Umbilical cord blood, which is usually collected immediately after a newborn baby s umbilical cord has been cut or from in utero placenta, contains a relatively large number of immature stem cells. They have the potential to develop into blood and immune cells as well as many other types of cell tissue. The harvesting of umbilical cord blood presupposes that the personnel who carry out the procedure have the experience necessary to collect an adequate number of cells under sterile conditions without adversely affecting either the mother or child. 1 The blood must then be taken to a cord blood bank within 24 hours for the separation and storage of the cells. Before the cells are isolated from the cord blood, information is collected concerning hereditary diseases, pregnancy complications, blood group, course of birth and any possible diseases from which the newborn baby is suffering particularly blood borne illnesses such as Hepatitis B and C, and HIV. Furthermore, HLA tissue typing is carried out. This typing 2 is necessary if the cells are not only to be used by the donor, but are to be transplanted into other recipients. HLA typing is used to identify the markers which are of crucial importance in determining whether tissue will be rejected or not and which must be compatible in both the donor and the recipient if rejection of a transplant is to be avoided. Using suitable techniques the stem cells are then isolated from the cord blood, frozen under precisely controlled conditions so that they are not damaged and then stored in liquid nitrogen at a temperature of minus 196 C. It is currently assumed that stored cord blood stem cells have the same properties as freshly isolated cells. However, so far, prospective data is only available for cells which have been stored for approximately 10 years. At present, statements regarding the functional properties of cells which are older than 10 years are not corroborated by prospective studies. 3 1 According to the European Group on Ethics in Science and New Technologies (EGE) Opinion 19, 16 March the number of cells to be transplanted should be measured so that a concentration of 2.0 x 10 7 /kg of body weight before freezing can be achieved. 2 HLA Typing: Human leukocyte antigens are proteins which express on the surface of the leukocytes and characterise an individual s cells. During typing, the proteins are identified. Identical or closely matching types of HLA are vital for the success of a transplant. 3 Expert reports on storage times vary between 9.2 years (American Society of Haematology Meeting, December 2007) and 15 years (EGE Opinion 19, 16 March 2004). Umbilical Cord Blood Banking, 19 May

2 Use of Cord Blood When using cord blood stem cells for transplants a distinction is made between allogeneic and autologous transplants. In the case of an allogeneic stem cell transplant, the cells are taken from a donor and given to another person. Allogeneic transplants are used to treat leukaemias, lymphomas, aplastic anaemia and genetic diseases of the blood and immune system. After the transplant, the haematopoietic stem cells can repopulate the patient's bone marrow and serve as the basis for the production of blood cells. 4 To date countless transplants worldwide have been carried out using cord blood from siblings and unrelated donors. 5 In Europe, cells for approximately 2% of allogeneic stem cell transplants are harvested from cord blood. In the past, it was believed that the quantity of stem cells in cord blood was only sufficient to achieve the lasting formation of blood in children with a body weight of less than 40 kg. 6 However, recent experience shows that it is possible to pool several cord blood samples in order to treat adults. 7 By combining six to eight units of cord blood it is now possible to obtain a quantity of cells that can be transplanted into men with a body weight of up to 100 kg. 8 The term autologous transplant refers to transplants where the donor and the recipient of the cells are one and the same person. Autologous transplants are currently only carried out following chemotherapy or radiotherapy. The aim of the transplantation is to repopulate the patient s bone marrow with his or her own haematopoietic stem cells which will then provide a source of blood cells. This type of autologous transplantation does not require the patient s own cord blood stem cells to have been obtained and stored at birth. Such transplants can be performed by harvesting stem cells from the patient before the therapy after stimulation by a growth factor. It is not possible to use autologous transplants with cord blood stem cells to treat genetic diseases of the blood and the immune system because the stem cells will carry the same genetic defects. Other therapies are also preferred for the treatment of leukaemia s and lymphomas. 4 See also, EGE Opinion 19, 16 March 2004 and Kryokonservierung von Nabelschnurstammzellen bei Neugeborenen zur eventuellen späteren Eigennutzung, Report of the Austrian Society for Haematology and Oncology, the Austrian Society for Blood Group Serology and Transfusion Medicine, Working Group for Haemotology/Oncology of the Austrian Society for Pediatrics and Adolescent Medicine (no date stated). 5 See also E Jäger, Geschichte und Zukunft der Transplantation von Nabelschnurstammzellen, February 2008, E. Gluckman (2001) Hematopoietic stem-cell transplants using umbilical-cord blood. N Engl, J Med 344: See, Kryokonservierung von Nabelschnurstammzellen bei Neugeborenen zur eventuellen späteren Eigennutzung, Report of the Austrian Society for Haematology and Oncology, the Austrian Society for Blood Group Serology and Transfusion Medicine, Working Group for Haemotology/Oncology of the Austrian Society for Pediatrics and Adolescent Medicine (no date stated). 7 See also., EGE Opinion 19, 16 March W Linkesch and C Gabriel in Junges Blut in Reserve, Der Standard, 4 February Umbilical Cord Blood Banking, 19 May

3 In 1988 it was discovered that the haematopoietic stem cells contained in cord blood can be used for allogeneic transplants to treat a number of hereditary diseases, serious blood diseases and immune system deficiencies. 9 However, the use of a patient's own cord blood stem cells for regenerative medicine is currently only a hypothetical possibility. Consequently, there are no indications to store cord blood at birth for future autologous transplant. In order to ensure a supply of stem cells from cord blood for transplantation purposes, cell banks operated by hospitals or non-profit organisations have been set up throughout the world. However, there are also privately-run commercial blood banks. Recently private companies have started offering, for a fee, to preserve the cord blood of newborn babies for potential future use by the same child or a family member. There are ethical objections to this, as there is currently no scientific data to support the effectiveness of an autologous transplantation with cord blood stem cells. The banking of cord blood cells can only be considered useful for intra-familial allogeneic grafts. 10 Intra-familial allogeneic transplants are only of interest in the case of rare HLA types or for families with an increased risk of specific forms of cancer or tumours. In these cases, it may be appropriate to bank the cord blood of newborn children in order to have cells available if they are needed for a member of the family (allogeneic transplantation). 11 In addition to their use for therapeutic purposes, cord blood stem cells are also used for research purposes and offer an additional valuable opportunity to research adult stem cells. This research is an important addition and possible alternative to the ethically controversial use of human embryonic stem cells and induced pluripotent stem cells which have recently become possible to generate. 9 For information regarding allogeneic transplants, see below: Use of umbilical cord blood. 10 See also NM. Fisk et al. Can Routine Commercial Cord Blood Banking Be Scientifically and Ethically Justified? PLoS Medicine, February 2005, Volume 2, Issue 2, e Guidelines of the Ministry of Health, Family and Youth: Diseases for which Umbilical Cord Blood of Siblings may be Frozen for Possible Allogeneic Stem Cell Transplant: acute and chronic leukemias, myelodysplastic syndrome, juvenile myelomonocytic leukaemia (JMML), haemophagocytic lymphohistiocytosis virus related or familial (HLH, FHL), severe combined immunodeficency disorder (SCID), combined immunodeficiency disorder (CID), Wiskott Aldrich Syndrome, Omenn Syndrome, Septic Granulomatosis/M.Kostmann, X-linked lymphoproliferative syndrome (XLP), severe aplastic anaemia (SAA), Fanconi anaemia, paroxysmal nocturnal hemoglobinuria (PNH), dyserythropoietic anaemia, Blackfan Diamond Anaemia, Thalassaemia major, sickle-cell anaemia; Accumulation diseases, metabolic disorders: adrenoleukodystrophy (ADL), late onset globoid cell leukodystrophy (GLD), juvenile metachromatic leukodystrophy ( MLD), mucopolysaccharidosis (MPS) Type I, VI, VII, osteopetrosis with the exception of the neuronopathic form, treatment-resistent auto-immune diseases. Umbilical Cord Blood Banking, 19 May

4 Advantages of Cord Blood Stem Cells for Allogeneic Transplants The advantages of stem cells harvested from umbilical cord blood compared to stem cells taken from adult donors is that cord blood stem cells are less immunologically mature and chronic infectious diseases are transmitted less frequently. This immunological immaturity means that stem cells from cord blood are less likely to induce immunological reactions, increasing the likelihood of a successful transplantation. Moreover, the collection of cord blood is non-invasive for the donor and therefore the number of potential donors is higher. The cells from cord blood are harvested and stored in advance and are therefore immediately available when needed for a transplant. Umbilical Cord Blood Banks At present there are approximately 100 cord blood banks worldwide. Seventy-five percent of the cord blood banks are public or private non-profit banks, which offer public service. They also store cord blood stem cells for intra-family use in the case of known risks in families with rare HLA types. 12 Twenty-five percent of cord blood banks are commercial operations which conserve cord blood cells for a potential future autologous use of their customers. In Austria there is currently only one bank for allogeneic grafts. It is run by the blood bank in Linz. Worldwide there are a large number of well-managed cord blood banks which hold cyropreserved cord blood stem cells for allogeneic transplantation in patients suffering from blood diseases and tumours. These blood banks must meet high technical, medical and logistic standards in order to supply high-quality products. 13 The international register for cord blood stem cells currently contains approximately 300,000 samples. 14 In Austria there are commercial cord blood banks for autologous use. 15 Other commercial banks operate in Germany, the Netherlands, Poland and the United Kingdom. Commercial cord blood banks are prohibited in Italy and Belgium. 12 See also, EGE Opinion 19, 16 March Allogene Nabelschnurblutbanken in Österreich, Report of the Austrian Society for Haematology and Oncology, the Austrian Society for Blood Group Serology and Transfusion Medicine, Working Group for Haematology/Oncology of the Austrian Society for Pediatrics and Adolescent Medicine (no date stated). 14 E Jäger, Geschichte und Zukunft der Transplantation von Nabelschnurstammzellen, February 2008, E Gluckman (2001) Hematopoietic stem-cell transplants using umbilical-cord blood. N Engl, J Med 344: See also, EGE Opinion 19, 16 March Umbilical Cord Blood Banking, 19 May

5 Legal Aspects There are no provisions in international law pertaining to cord blood banking. However, Article 21 of the Convention on Human Rights and Biomedicine can impact the operation of cord blood stem cell banks and the collection of the blood, as it stipulates that the human body and its parts shall not, as such, give rise to financial gain. In the case of allogeneic transplants, the Second Additional Protocol to the same Convention concerning the transplantation of organs and tissue of human origin applies, as according to Article 2 para. 2, the provisions of the Protocol applicable to tissues also apply to cells, including haematopoietic stem cells." However, as Austria is not a signatory to the biomedicine convention, these provisions are not legally binding in Austria. However, reference can be made to a recommendation of the European Health Committee of the Council of Europe, REC (2004)8 of 19 May It recommends to its member states that: - If cord blood banks are established, they shall be from altruistic and voluntary cord blood donation and used for allogeneic transplantation and related research. - The promotion of donation for autologous use and the establishment of cord blood banks for autologous use should not be supported by member states or their health services. - Accurate information should be provided to the population about the advantages and disadvantages of cord blood banks. - Where autologous cord blood banks are being established, the promotion material or information provided to families must be accurate, and fully informed consent to cord blood storage must be obtained. - Autologous cord blood banks that are being established must meet the quality and safety standards set out in the Council of Europe s Guide to safety and quality assurance for organs, tissues and cells. Within the European Union, the Directive setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (Directive 2004/23/EC 16 ) must be observed. In Austria this is implemented in national law in the Tissue Safety Act (Gewebesicherheitsgesetz - GSG), Federal Law Gazette I 2008/49. While this Directive like the Tissue Safety Act excludes blood and blood products from its 16 In addition the following directives also apply: Commission Directive 2006/17/EC implementing Directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells; Commission Directive 2006/86/EC implementing Directive 2004/23/EC of the European Parliament and of the Council as regards traceability requirements, notification of serious adverse reactions and events and certain technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells. Umbilical Cord Blood Banking, 19 May

6 scope of application, haematopoietic progenitor cells are subject to both the European Tissue Directive (see also Recital 8) and the Tissue Safety Act. In the past, the legal framework for collecting umbilical cord blood was essentially provided by the Pharmaceuticals Act (Arzneimittelgesetz AMG). Blood could only be collected by hospitals which possessed an operating permit pursuant to Article 65 in conjunction with Article 63 of the Pharmaceuticals Act. The prerequisite for collection was that the cord blood would be handed over to an organisation which was in possession of a licence to process and store the cells and that the consent of the mother/parents had been obtained. Following the enactment of the Tissue Safety Act on 30 March 2008, the extensive provisions of this law apply to the collection, processing, storage and distribution of cord blood stem cells. In future, blood may only be taken at collection facilities which are required to report to the Austrian Agency for Health and Food Safety. Existing collection facilities (hospitals) must file a report within six months of the Tissue Safety Act coming into force (Article 37 GSG). In addition to this, under Article 22 of the Act, cord blood banks are required to have an official permit. However, a permit for tissue banks (and arguably for collection facilities) pursuant to pharmaceutical law is no longer necessary (Article 62 para. 2. line 4, Pharmaceuticals Act). Among other things, the Tissue Safety Act lays down detailed requirements regarding the duty to obtain the fully informed consent of the patient (Article 4 para. 3 Tissue Safety Act) for both the collection and further use of the cells. Article 4 para. 6 of the Tissue Safety Act explicitly prohibits the granting or promising of financial gain or a comparable advantage to donors of cells or tissues or third persons in exchange for a donation. However, the granting of appropriate compensation for loss of earnings and other justifiable expenses caused by the removal and by the related medical measures, and the award of compensation for injury suffered as a result of the removal and the other related medical measures is permissible (Article 4 para. 7 Tissue Safety Act). In accordance with the recommendations of the Supreme Health Council that aggressive advertising in hospitals by commercial cord blood banks should be prohibited, that no financial compensation may be offered for customer acquisition, gynaecological and obstetric departments have been instructed, among other things, to: 17 - Prohibit all forms of advertising for the collection of umbilical cord blood for autologous use at the hospitals. - To restrict the opportunities for contact between commercial cord blood banks and personnel who are authorised to take blood to necessary training sessions. - Ensure that a doctor from the respective gynaecological and obstetric department informs the mother with regard to the collection and storage of cord blood. 17 Resolution of the 10th Full Assembly of the Supreme Health Council on 24 May Umbilical Cord Blood Banking, 19 May

7 - Leave the decision regarding the possibility of collecting blood solely to the attending physician (due to the medical situation). - To lay out only brochures published by the Ministry of Health, Family and Youth as information material. Critical Ethical Evaluation Since it became possible to separate cord blood stem cells and use them for research and medical purposes, Austria too finds itself facing the challenge of having to respond to the national and international debate concerning an ethical judgement of the opportunities generated by the collection and storage of cord blood stem cells. The benchmark for the ethical evaluation of the collection, storage and use of stem cells from cord blood is provided by internationally recognised fundamental medical and ethical principles. These are: - The principle of respect for human dignity; - The right to physical and mental integrity; - The principle not to exploit the human body and its parts for obtaining financial gain; - The principle of autonomy or the right to self-determination, specifically: voluntary consent on the basis of full and complete information (informed consent); - The principle of beneficence, which refers to using medical measures for the well-being of the patient; - The obligation not to do harm; - The principle of justice; - The principle of proportionality, which implies a balance between the means and the objectives. Due to the fact that cord blood is collected in a non-invasive procedure performed by experienced personnel and involves no danger to the mother or child, the right to physical and mental integrity is satisfied. As it can be assumed that the existing standards relating to the prohibition of financial benefits in exchange for a human tissue donation will also apply to donations of cord blood, the principle that the human body and its parts may not be used to obtain financial gain is satisfied (principle of non-commercialisation or noncommoditisation). The principle of autonomy and the right to self-determination is satisfied by the requirement for the written consent of the mother / parents for the collection of cord blood and its use. Furthermore, the criterion of autonomy is satisfied as in hospitals only information brochures compiled by the Ministry of Health, Family and Youth may be laid out, thus ensuring that only correct and precise information is given to families before they consent to the collection of cord blood for autologous use. Umbilical Cord Blood Banking, 19 May

8 The principle of beneficence, i.e. the use of medical measures for the well-being of the patient, is satisfied in the case of the collection of cord blood for later use if a genuine medical benefit can be derived for the party concerned. This is true in the case of intra-familial allogeneic transplants for rare HLA types, for families with an increased risk of certain tumours or where scientific knowledge will be advanced for the benefit of future patients. In Austria, the provisions of the Tissue Safety Act and the approvals required under the terms of the Act adequately guarantee the reliability of cord blood banks in terms of quality and safety standards, so that the obligation to do no harm is fulfilled. Furthermore, the principle of non-maleficence is brought to bear by the firm requirement that ultimate responsibility in connection with the collection of cord blood rests with the attending gynaecologist. This guarantees that the collection of cord blood will not impair the birthing process. With regard to the principle of justice, a distinction has to be drawn between a number of concepts: Distributive justice, fair exchange and community welfare justice as well as, in particular, participatory and enabling justice, which ensure equitable health care system access for all and create the conditions which enable individuals effectively to assume the personal responsibility for their own health which is increasingly expected today. When discussing the allocation of resources in the health services, these various concepts of justice have to be applied. Thus, the discussion in respect of the profit orientation of cord blood banks must also be viewed within the context of debates about the public health care service, its funding on the basis of social insurance contributions and the trend toward a privately funded health care system. Recommendations Based on the principle of justice and solidarity with regard to equal access to health care, the Bioethics Commission recommends that in the context of allogeneic transplants, greater support should be given to public and private non-commercial cord blood banks which contribute to public welfare. The Bioethics Commission recommends that in consideration of the principle of community welfare justice, potential donors should be informed of the possibility to donate cord blood for the purposes of allogeneic transplantation and that, in consideration of the principle of community welfare justice, potential donors should also be informed of the possibility of donating cord blood for research purposes. However, the Bioethics Commission does not recommend the storage of cord blood stem cells for autologous transplantation at present. Umbilical Cord Blood Banking, 19 May