Ethical considerations of using a single minor donor for three bone marrow harvests for three HLA-matched siblings with primary immunodeficiency.

Allogeneic hematopoietic stem cell transplantation is curative for primary immunodeficiencies. Bone marrow from an unaffected human leukocyte antigen (HLA)-identical sibling donor is the ideal graft source. For minor donors, meaningful consent or assent may not be feasible, and permission from parents or legal guardians is considered acceptable. Adverse events, albeit extremely small, can be associated with bone marrow harvest in pediatric donors. Donor safety concerns potentially increase with multiple bone marrow harvests. Very little is known about multiple bone marrow harvests from pediatric donors. We describe the ethical considerations and clinical decision-making in an unusual clinical situation where three patients with the same primary immunodeficiency were HLA identical to one another and their younger sibling, who underwent bone marrow harvests three times between 1.3 and 4 years of age, resulting in successful transplantation for all three patients. We hope that this experience will provide guidance to providers and families in a similar situation.

[General and ethical considerations for the informed consent process: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Considérations générales et éthiques pour le recueil d'un consentement éclairé : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Informed consent is not restricted to clinical research and must be applied to high-risk care such as hematopoietic stem cell transplantation. If standardized informed consent might improve inequalities in medical practices between different transplantation centers, it is strongly recommended that it be adapted with an honest dialogue between physicians and patients and physicians and donors. In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. The purpose of this paper is to highlight the French law concerning patients' rights and ethical practices for an informed consent process to be applied to care or research.

The Interfamilial Principle and the Harvest Festival.

It is widely accepted that younger children can act as saviour siblings by donating cord blood or bone marrow to their gravely-ill brothers or sisters. However, it is under dispute whether these procedures are in the best interests of the child. This article suggests that parents may be relying on a thinly-veiled interfamilial approach, where the wider benefit to the whole family is used to justify the procedure to the Human Tissue Authority in the United Kingdom. This article suggests that the merging of familial interests to validate a non-therapeutic bone marrow harvest on a child forces altruism in a patient too young to understand, rendering the harvests unlawful under current law.

Pressure placed on paediatric haematopoietic stem cell donors: Views from health professionals.

AIM: Paediatric haematopoietic stem cell donors undergo non-therapeutic procedures and endure known and unknown physical and psychosocial risks for the benefit of a family member. One ethical concern is the risk that they may be pressured by parents or health professionals to act as a donor. This paper adds to what is known about this topic by presenting the views of health professionals. METHODS: This qualitative study involved semi-structured interviews with 14 health professionals in Australasia experienced in dealing with paediatric donors. Transcripts were analysed using established qualitative methodologies. RESULTS: Health professionals considered that some paediatric donors experience pressure to donate. Situations that were likely to increase the risk of pressure being placed on donors were identified, and views were expressed about the ethical 'appropriateness' of these practices within the family setting. CONCLUSIONS: Children may be subject to pressure from family and health professionals to be tested and act as donors, Therefore, our ethical obligation to these children extends to implementing donor-focused processes - including independent health professionals and the appointment of a donor advocate - to assist in detecting and addressing instances of inappropriate pressure being placed on a child.

Savior siblings, parenting and the moral valorization of children.

Philosophy has long been concerned with 'moral status'. Discussions about the moral status of children, however, seem often to promote confusion rather than clarity. Using the creation of 'savior siblings' as an example, this paper provides a philosophical critique of the moral status of children and the moral relevance of parenting and the role that formative experience, regret and relational autonomy play in parental decisions. We suggest that parents make moral decisions that are guided by the moral significance they attach to children, to sick children and most importantly, to a specific sick child (theirs). This moral valorization is rarely made explicit and has generally been ignored by both philosophers and clinicians in previous critiques. Recognizing this, however, may transform not only the focus of bioethical discourse but also the policies and practices surrounding the care of children requiring bone marrow or cord blood transplantation by better understanding the values at stake behind parental decision making.

Acesso aos transplantes de medula óssea no Brasil: uma questão de justiça / Access to bone marrow transplants in Brazil: a question of justice

Este trabalho investiga a questão da distribuição dos transplantes de medula óssea abordada a partir do princípio da justiça, entendido como equidade no acesso a esse benefício terapêutico no contexto brasileiro. O trabalho se inicia contextualizando os problemas éticos levantados pelo desenvolvimento das pesquisas com células tronco e as perspectivas terapêuticas promissoras associadas a tais pesquisas. A questão da justiça enquanto oportunidade de acesso a todos aos benefícios terapêuticos resultantes dessas pesquisas é considerada, nesse contexto, uma questão moral crucial. O transplante de medula óssea é um caso concreto de aplicação terapêutica bem-sucedida resultante das pesquisas com células-tronco. Esta é uma terapia eficaz para o tratamento de dezenas de doenças do sangue, bem estabelecida em âmbito global, inclusive no Brasil. No entanto, garantir o acesso de todos a ela não é tarefa fácil de realizar em contextos como o latinoamericano, incluindo o brasileiro, nos quais os recursos escassos conflitam com as imensas demandas na área da Saúde. O objetivo geral da investigação foi examinara prática do transplante de medula óssea no contexto brasileiro, a fim de saber se esta preenche os requerimentos do princípio da justiça como equidade, garantindo oportunidade de acesso a esse benefício a todos os que dele necessitarem, segundo a medida deste princípio. Metodologicamente trata-se de uma discussão teórica e crítica secundada por elementos qualitativos de um estudo de caso sobre os transplantes de medula óssea no Brasil. Discutimos inicialmente o conceito de justiça como equidade, investigando os fundamentos teóricos da ética dos direitos humanos e os fundamentos da concepção de justiça de Amartya Sen. Completamos esse referencial teórico com o exame da contribuição proposta pela bioética da proteção...

Com isso, pretendemos ter alcançado um adequado conceito de justiça como equidade. Passamos então à análise do contexto brasileiro, visando a saber das condições de possibilidade que tal contexto oferece para a prática da justiça no campo sanitário. Nesse sentido, analisamos o direito formal à saúde inscrito no Sistema Único de Saúde, em contraste com as imensas desigualdades que predominam no país e as iniquidades em saúde. Exploramos as diversas incongruências do sistema público de saúde, o papel do Estado e a importância da participação social. Examinamos, por fim, o sistema de transplantes de medula óssea no Brasil e as diversas espécies de dificuldades que o desafiam na tentativa de agir com justiça. A conclusão é que, embora o sistema seja sensível aos problemas bioéticos que cercam essa atividade e considere os requerimentos da justiça na distribuição dos transplantes, a equidade no acesso a esse benefício terapêutico ainda é uma exigência difícil de ser realizada em razão das características do contexto brasileiro...

The present study uses the justice theory principles to investigate how bone marrowtransplant is allocated in the Brazilian health context and how equitable is theBrazilian population access to this therapy. The first part of the study is dedicated toidentify the ethical issues brought up by the development of stem-cell researches andits outcomes. Justice theory brings a compelling moral issue to this scenario. Bonemarrow transplant is a successful application of stem cell researches and has beenstablished as an efficient therapy for several blood diseases. However, it has beendifficult to guarantee universal access to this therapy in Latin America, where limitedresources are constantly challenged by huge health care needs. The objective of thisstudy is to evaluate if equity parameters are taken into consideration in thedistribution of bone marrow transplant procedures in Brazil, according to justicetheory principles. Amartya Sen’s ideas of human rights ethics and justice are thebasis for our discussion of justice as equity. Theoretical approach is complementedby the conceptual framework of the protection bioethics so as to achieve a broaderconcept of justice as equity that could be applied to the Brazilian health context. Howuniversal access to health care in Brazil is actually operationalized in view of themassive inequalities of the country. Health care system characteristics andcontradictions, the rule of the state and the importance of social control are alsoanalysed in the study. The difficulties faced in access of bone marrow transplants arealso examined in view of the bioethic challenges to regulate state actions and rightswith justice principles. Conclusions show that the health care system considersjustice and bioethics arguments in the managing of bone marrow transplants,however equity in access of such therapy is hardly achieved...

Subsequent donation requests among 2472 unrelated hematopoietic progenitor cell donors are associated with bone marrow harvest.

Approximately 1 in 20 unrelated donors are asked to make a second donation of hematopoietic progenitor cells, the majority for the same patient. Anthony Nolan undertook a study of subsequent hematopoietic progenitor cell donations made by its donors from 2005 to 2011, with the aims of predicting those donors more likely to be called for a second donation, assessing rates of serious adverse reactions and examining harvest yields. This was not a study of factors predictive of second allografts. During the study period 2591 donations were made, of which 120 (4.6%) were subsequent donations. The median time between donations was 179 days (range, 21-4016). Indications for a second allogeneic transplant included primary graft failure (11.7%), secondary graft failure (53.2%), relapse (30.6%) and others (1.8%). On multivariate analysis, bone marrow harvest at first donation was associated with subsequent donation requests (odds ratio 2.00, P=0.001). The rate of serious adverse reactions in donors making a subsequent donation appeared greater than the rate in those making a first donation (relative risk=3.29, P=0.005). Harvest yields per kilogram recipient body weight were equivalent between donations, although females appeared to have a lower yield at the subsequent donation. Knowledge of these factors will help unrelated donor registries to counsel their donors.

Trouble in the gap: a bioethical and sociological analysis of informed consent for high-risk medical procedures.

Concerns are frequently raised about the extent to which formal consent procedures actually lead to "informed" consent. As part of a study of consent to high-risk medical procedures, we analyzed in-depth interviews with 16 health care professionals working in bone-marrow transplantation in Sydney, Australia. We find that these professionals recognize and act on their responsibility to inform and educate patients and that they expect patients to reciprocate these efforts by demonstrably engaging in the education process. This expectation is largely implicit, however, and when it is not met, this can give rise to trouble that can have adverse consequences for patients, physicians, and relationships within the clinic. We revisit the concept of the sick role to formalize this new role expectation, and we argue that "informed" consent is a process that is usually incomplete, despite trappings and assumptions that help to create the illusion of completeness.

Ethical issues in bone marrow transplantation in children.

In the 50 years since the first successful human bone marrow transplant (BMT) was performed in 1959, BMT has become the optimal therapy for a wide variety of life-threatening paediatric haematological, immunological and genetic disorders. Unfortunately, while BMT generally provides the only possibility of cure for such afflicted children, few (25%) have a matched sibling available, and suitably matched unrelated donors are often not identified for many children in need of BMT. And even where BMT is possible, treatment is complex and arduous and associated with significant mortality and morbidity. The issues raised when either or both the donor and recipient are children and lack the capacity to make informed and rational decisions relating to BMT pose great challenges for all involved. This paper examines some of the ethical dilemmas that confront patients, families and medical practitioners when considering bone marrow transplantation in a child.

Saviour-sibling and the psychological, ethical and judicial issues that it creates: should English and French legislators close the Pandora's Box?

Since the advent of test-tube babies, advances in the biomedical field have risen steadily. In parallel, the scientific body has never since ceased to debate the ethical issues that they arise. This is particularly the case regarding saviour-sibling. Saviour-sibling refers to a child who is conceived to cure an older brother or sister suffering from a serious family genetic disease. Therefore, it is meant to give birth to a child who will provide stem-cells taken from the umbilical cord or bone marrow afterwards, to treat an elder sick sibling. In England, this practice has been explicitly allowed by the new Human Fertilisation and Embryology Act 2008 under some strict conditions. In France, this practice, authorized by the Bioethics Law of August 2004 and confirmed by its decree of implementation published in the Official Journal on 23 December 2006, is also strictly regulated. This technique opens up new perspectives and enormous hope. Its legalisation is certainly justified by the suffering of the parents and to avoid that they travel to other States where it is permitted. However, it raises serious psychological ethical and judicial issues. Following an analysis of the English and French laws on saviour siblings, its controversial side will be highlighted, before concluding whether or not this new Pandora's box which is saviour-sibling, should be closed and other alternative methods encouraged.

Bone marrow transplantation in the prevention of intellectual disability due to inherited metabolic disease: ethical issues.

Many inherited metabolic diseases may lead to varying degrees of brain damage and thus also to intellectual disability. Bone marrow transplantation (BMT) has been used for over two decades as a form of secondary prevention to stop or reverse the progress of the disease process in some of these conditions. At the population level the impact of BMT on the prevalence of intellectual disability is minute, but at the individual level its impact on the prognosis of the disease and the well-being of the patient can be substantial. The dark side of BMT use is the burden of side effects, complications and transplantation-related mortality in less successful cases. The ethical issues involved in this therapy are discussed in this review.

Experimental animal models of myocardial damage in regenerative medicine studies involving adult bone marrow derived stem cells: ethical and methodological implications.

Cardiac performance after myocardial infarction is compromised by ventricular remodeling, which represents a major cause of late infarct-related chronic heart failure and death. In recent years, the scientists' interest has focused on the hypothesis that the administration of bone marrow progenitors, following myocardial infarction, could ameliorate left ventricular remodeling by continuing to differentiate along the haematopoietic lineage. This approach has been developed minding to the consolidated use of transfusions to restore lost or depleted blood components and, therefore, as an enriched dose of various progenitors, generally autologous, injected peripherally or directly in the infarcted area. Since the safety of this therapy was not yet established, for ethical reasons pioneering researchers involved in these studies used animal models as surrogate of the human biologic system. Herein this hypothesis of therapy resulted in an increased use of living animals and in the reappraisal of models of myocardial damage with limited discussion on the theoretical basis of animal models applied to cell-based therapies. Recently, the European Union and its commission for surveillance of laboratory animals advanced a new proposal to restrict the use of living animals. This review will focus on the history of models utilization in biomedicine, with particular attention to animal models, and delineate an operative comparison between the two best known models of myocardial injury, namely coronary ligation and cryodamage, in the perspective of adult stem cell research applied to cardiovascular regenerative medicine.

Ethical reasoning about patient eligibility in allogeneic BMT based on psychosocial criteria.

Chairpersons of the hospital ethics committees (HECs) and BMT clinicians were compared with regard to their willingness to proceed with allogeneic BMT given select psychosocial risk factors. A self-administered questionnaire was sent to 62 HEC chairpersons at hospitals with an accredited BMT program; the response rate was 37%. Items included background information, followed by six case vignettes from a 2006 national survey on which BMT physicians, nurses and social workers agreed not to proceed with allogeneic BMT on the basis of the following risk factors: suicidal ideation; use of addictive, illicit drugs; history of non-compliance; absence of a caregiver; alcoholism; and mild dementia from early onset of Alzheimer's disease. Opinions regarding transplant differed in one case only, in a patient with mild dementia; 27% of HEC chairpersons recommended not proceeding with BMT, which was significantly lower than that of nurses (68%, P<0.001), physicians (63.5%, P<0.001) and social workers (51.9%, P=0.05). Qualitative data show patterns of informal reasoning, linking transplant decisions to patient's responsibility for their psychosocial risk factor(s), as well as to medical benefit and outcome.