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Title
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The Policy Statement of the American Academy of Pediatrics – Children as
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Hematopoietic Stem Cell Donors – a proposal of amendments for better
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protection of minors
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Authors’ names
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CHAN Tak Kwong
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Assistant Professor, Anatomy, University of Hong Kong
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Email: theo@hku.hk; Tel: 852-93863620; Fax: 852-28199205
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Postal Address: L1-59, Laboratory Block, 21 Sassoon Road, Hong Kong
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TIPOE George Lim
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Associate Professor, Department of Anatomy, University of Hong Kong,
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Hong Kong
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Postal Address: L1-59, Laboratory Block, 21 Sassoon Road, Hong Kong
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Correspondence to CHAN TK at theo@hku.hk
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Word count: 2085
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Keywords: policy, haematopoietic stem cell transplant, ethical concerns, donor
siblings
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Abstract:
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With a view to addressing the moral concerns about the use of donor siblings, the
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Policy Statement of the American Academy of Pediatrics - Children as Hematopoietic
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Stem Cell Donors (the Policy) has laid out the criteria upon which tissue harvest from
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a minor would be permissible.
Background
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Discussion
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Although tissue harvest serves the best interests of recipient siblings, parents are also
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obliged to act in the best interests of the donor sibling. Tissue harvest should proceed
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if and only if it serves the best interests of both the donor and recipient. Parents
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should be forbidden, and they are by law, to consent to tissue harvest unless there are
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substantial benefits for an incompetent minor that can outweigh the potential harm.
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There is no basis to subject a minor to the medical risks of tissue harvest if the
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recipient sibling can wait without significant risks of complications until the donor
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becomes Gillick competent. We also argue that the Policy fails to take into account
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recent advances in haematopoietic transplantation from haploidentical donors or
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related tissue-matched donors. As a proper ethical evaluation should have regard to
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the availability of different types of suitable donors, fulfilling the criteria specified in
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the Policy alone is not sufficient to justify tissue harvest from a donor sibling.
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Summary
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Unless a recipient sibling will suffer from serious complications or die without the
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transplantation and no other medically equivalent donors are available, there is no
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moral or legal basis to violate the donor sibling’s right to bodily integrity.
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Accordingly, we propose that the Policy should be revised in order to fully address
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our moral concerns in relation to tissue harvest from donor siblings.
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BACKGROUND
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In conjunction with preimplantation genetic diagnosis (PGD), assisted reproduction
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can be used to avoid inheritable diseases. After successful in-vitro fertilization, PGD
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can identify whether any of the embryos is affected by a genetic condition. Parents
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now can even request selection of embryos on the basis of tissue type in order to
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create a child to cure an existing sick child. In response to the moral concerns about
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the use of paediatric haematopoietic cell donor siblings (donor siblings), the Policy
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Statement of the American Academy of Pediatrics – Children as Hematopoietic Stem
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Cell Donors (the Policy) suggests that tissue harvest should only proceed upon
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satisfaction of all the following five criteria:
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‘(1) there is no medically equivalent histo-compatible adult relative who is willing
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and able to donate;
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(2) there is a strong personal and emotionally positive relationship between the donor
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and recipient;
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(3) there is some likelihood that the recipient will benefit from the transplantation;
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(4) the clinical, emotional, and psychosocial risks to the donor are minimized and are
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reasonable in relation to the benefits expected to accrue to the donor and to the
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recipient; and
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(5) parental permission and, where appropriate, child assent have been obtained.’1
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Except that the fourth criterion requires the physician to minimise the risks of medical
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procedures by, e.g. avoiding central venous catheter insertion and reducing
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psychological risk by proper communication skills and the fifth requires that child
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assent should be obtained where appropriate, the remaining criteria seem to merely
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state the facts common to most cases of tissue harvest rather than regulating the
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process. We contend that the Policy fails to sufficiently protect the interests of donor
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siblings without addressing the availability of other types of donors and the type of
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disease.
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DISCUSSION
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The legal and ethical principles
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One would not dispute that tissue harvest serves the best interests of recipient siblings.
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As one’s liberty cannot be allowed to such an extent that another person suffers
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harm,2 a donor sibling does not have an obligation to save the life of the recipient
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sibling given the medical risks of transplantation. A Gillick competent donor should
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be free to make an informed decision of whether to save the life of a recipient
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sibling.3 In case the donor sibling is an incompetent minor, a parent must proceed to
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assess the best interests of the donor. The assessment of best interests is a balance of
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the benefits and risks of transplantation for the donor. The procedures need not be risk
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free but parents should only consent to tissue harvest if the possible benefits for the
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donor outweigh the potential harm. Although parents have the rights to make
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decisions for incompetent minors, the Children Act 1989 in the United Kingdom
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empowers the court to intervene if parents fail to act in the best interests of both
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children.4, 5 In Birmingham City Council v H (a minor), Balcombe LJ said the
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question of welfare of both children should be approached ‘without giving one
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priority over the other.’6 Although the parents’ wishes should command very great
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respect, the court is to exercise an independent and objective judgment.7 The ethical
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principles of beneficence and non-maleficence also demand that parents should
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consent to tissue harvest only if it serves the best interests of both the donor and
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recipient.
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The best interests of donor siblings
Well-documented risks
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The most ethically sound basis to oppose tissue harvest is that it imposes risks of
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bodily injuries associated with the medical procedures of tissue harvest. The risks
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depend on the source of cells namely bone marrow, peripheral blood and umbilical
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cord blood, each with their own benefits and risks. It is known that harvest by
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umbilical cord blood carries no medical risks except in case of modified delivery.
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Therefore my analysis below focuses on bone marrow and peripheral blood
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transplantation only. Minor complications like pain at collection sites, fatigue and
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pain may occur in a small proportion of donors (6%-20%). Major and life-threatening
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complications following marrow donation like anesthesia-related events, injuries to
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bones, sacroiliac joint and sciatic nerve were estimated to occur in 0.1%-0.3% of
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cases.8 Major risks of peripheral blood transplantation are mainly associated with
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sedation, general anaesthesia and central venous catheter insertion, estimated to be
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about 1.1% of cases.9 In light of one’s inviolable right to bodily integrity, minors
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should not be exposed to the medical risks unless there are well-established benefits
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of a significant magnitude that they can accrue from tissue harvest.
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Potential benefits
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The possible benefits for donor siblings are merely psychosocial. In an American case
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Curran v. Bosze, Calvo J said that ‘the psychological benefit is grounded firmly in the
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fact that the donor and the recipient are known to each other in a family. There may be
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a psychological benefit to the child from donating bone marrow to a sibling.’10 We
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consider that tissue harvest can have short-term and long-term psychosocial effects
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for donor siblings. When presented with the idea of donation, younger donors were
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found to focus more on the immediate pain and the frightening experience of the
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procedure,12 whereas older children might feel pressure from family members or
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medical staff to become a donor.11 MacLeod and others found that about a third of the
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siblings donors thought that doctors and family members limited their opportunity to
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say no, making them perceive they had a ‘forced no choice’.12 And donor siblings
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reported higher levels of anxiety and lower self-esteem than non-donor siblings,13
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which may be attributed to the lack of choice in the decision to donate. It follows that
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a donor sibling is more likely to have short-term psychosocial burdens rather than
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benefits.
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Long term positive effects for the donor siblings include greater sensitivity to the
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needs of others14, enhanced self-sufficiency and independence15, increased family
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closeness16, and most important of all, the possible companion of a healthy recipient
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sibling. On the other hand, negative emotions were reported when their recipient
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siblings developed long-lasting complications from the procedure. Furthermore,
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anger, guilt, and blame were common amongst donor siblings with unsuccessful
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transplant.12 While the Policy cited the findings of three studies that all donor siblings
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agreed that the psychosocial benefits and harm of serving as a donor outweighed the
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physical harms, Macleod,Wieners and others found that only 66.6% and 67% of
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donor siblings reported a predominantly positive psychosocial experience.12, 17
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Importantly, all reporting predominantly positive psychosocial experience had
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successful transplant and only donors with unsuccessful transplant reported a
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predominantly negative experience in Macleod’s study.12 As the psychosocial
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experience is highly associated with the outcome for the recipient, we contend that the
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long-term benefits for donor siblings mainly derive from the survival of the recipient
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sibling rather than from process of tissue harvest per se.
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Balance of benefits and risks
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Whereas the advantages of tissue harvest for donor siblings are long-term and merely
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psychosocial, the other side of balance sheet consists of short-term psychological
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burden and life-threatening physical harm. One should bear in mind that the notion of
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benefits and risks are both relative concepts. To consider the potential gains or losses
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for donor siblings, we ought to consider what would likely happen to the donors and
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recipients without tissue harvest. It cannot be said that tissue harvest can offer any
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significant long-term benefits for the donor sibling if other available source of
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transplant can offer a similar chance of success or if the sick sibling can survive
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without serious complications even without transplantation. Those who do not agree
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may argue that a donor sibling may in the future relish and take pride in being a donor
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and therefore still want to donate even if other donors are available. Parents may
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legitimately consider this factor when making decisions for incompetent minors. But
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the remoteness of this benefit should take its edge off from the evaluation. The sense
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of pride may not materialize if the grown-up donor sibling does not accept the filial or
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social responsibility to save the recipient sibling, is disinterested in altruistic donation,
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or does not relish in living in the shadows of the recipient sibling. In any event, it is
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only for a competent individual to decide whether they want to take the risks in
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exchange for just the goodwill and the pride of being ‘a donor and a saviour’. For
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minors, we hold that the benefits of this alone are too remote and small in magnitude
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to justify the medical risks of life-threatening bodily intrusion. In short, the only
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circumstance where tissue harvest would serve the best interests of a minor donor is
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that without the proposed transplantation taking place, the sick sibling will more
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likely suffer serious complications or die.
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Availability of other donors
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In light of foregoing discussion, to determine whether tissue harvest is in a donor
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sibling’s best interests, one should assess first whether the recipient sibling would
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likely die or suffer from serious complications without a transplantation. If the answer
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is affirmative, then one should see if donation from any mentally competent donors
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can offer a similar chance of successful transplantation.
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In the past, tissue-matched related donors were considered to be the best sources of
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donation. But now, many drawbacks of unrelated or haplo-identical transplants such
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as graft failure and significant graft-versus-host diseases have been overcome due to
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the development of new extensive T-cell depletion techniques with mega dose stem
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cell administration over the last two decades. New approaches such as alloreactive T
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cell depletion and post-transplant cell therapy have also improved immune
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reconstitution in tissue-matched unrelated or haplo-identical transplants. Using haplo-
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identical donors are now considered to be equally safe and effective transplant
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strategies as tissue-matched donors for advanced leukemia.18 Leung and others
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showed that the five year survival rates of recipient siblings with high risk leukemia
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are promising regardless of donor types (68% for donor siblings, 74% for unrelated
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donors and 77% for haplo-identical donors), and that the risks of death from graft-
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versus-host diseases at five years is not significantly associated with the types of
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donors (6.6% for donor siblings, 7.0% for unrelated donors, and 3.4% for haplo-
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identical donors).19 Therefore, a search for competent family members, local and even
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international bone marrow donor registry should be undertaken before parents are
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permitted to consent to tissue harvest from donor siblings for recipients suffering
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from advanced lymphoma or leukemia. For other diseases, Sodani and others reported
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that haplo-identical transplant in thalassemia has 93% chance of survival and only 7%
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mortality using new conditioning regimen.20 Bolaños-Meade and others showed that
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the use of haplo-identical transplant for patients with sickle cell disease is highly
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effective and safe despite the fact that graft failure still remains an obstacle.21
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Proposed amendments of the Policy
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It is already well established that the use of haplo-identical transplant is equally safe
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and effective for advanced lymphoma or leukemia, whereas studies are still underway
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to evaluate the results with non-malignant diseases like aplastic anemia, lupus and
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sickle cell diseases. The above literature search by no means suggests that haplo-
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identical transplant can replace tissue-matched transplant but, given the success of
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new regimens of transplantation, doctors should look beyond the availability of
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tissue-matched related donors for certain types of diseases. Parents and doctors should
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make sure, if the medical conditions of the sick sibling permit a search, that no other
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sources of equally or similarly effective transplant are available before subjecting a
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minor to the physical risks and short-term psychological harm of tissue harvest.
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In the circumstances, I propose that the following should replace the original first and
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third criteria in the Policy:
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1. If the medical conditions of the recipient permit a search, there is no medically
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equivalent haplo-identical/histo-compatible adult who is willing and able to
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donate;
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3. The recipient sibling will likely suffer from serious complications or die
without transplantation before the donor sibling becomes Gillick competent,
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CONCLUSIONS
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The parental choice to harvest tissues from donor siblings reflects the immense
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‘emotive desire to do something to help the recipient sibling’.22 However, donor
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siblings may not necessarily reap any benefits in light of the risks of serious injuries
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arising from bone marrow or peripheral blood transplantation. Fulfilling the criteria
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specified in the Policy of the Academy alone is not sufficient to justify tissue harvest
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from minors. Unless a recipient sibling will likely suffer from serious complications
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or die without the transplantation and no tissue-matched unrelated donors or related
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haploidentical donors are available, there is no moral or legal basis to violate the
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donor sibling’s right to bodily integrity. In short, the Policy should be revised to fully
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address our moral concerns in relation to tissue harvest from minor donor siblings.
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Competing interests
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1
The authors declare that they have no competing interests.
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Author’s Contributions
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Corresponding and first author Chan TK is the main researcher, writer and editor
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responsible for the legal research and ethical analysis.
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The co-author Tipoe GL, was responsible for identifying ethical issues, overseeing the
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research and giving expert input into the ethical analysis and review. Both authors
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read and approved the final manuscript.
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Authors’ Information
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CHAN TK, MBChB, MRCS, LLM(Medical Law and Ethics)
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Assistant Professor
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Anatomy
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University of Hong Kong
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L1-59 Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong
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Kong
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TIPOE GL, MD, PhD
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Asscoiate Professor
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Anatomy
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University of Hong Kong
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1/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong
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26
Acknowledgements
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We would like to thank the reviewers Dr Wendy Rogers, Dr Joerg Halter, Dr Elaine
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Morgan and Dr Heidi Mertes for their invaluable comment in revision of the
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manuscript.
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Funding
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Funding not required
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Ethical Approval
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Ethical approval not required.
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8
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