Review Transplant of Bone Marrow and Cord Blood Hematopoietic Stem Cells in Pediatric Practice, Revisited According to the Fundamental Principles of Bioethics
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Bone Marrow Transplantation, (1997) 19, 1163–1168 1997 Stockton Press All rights reserved 0268–3369/97 $12.00 Review Transplant of bone marrow and cord blood hematopoietic stem cells in pediatric practice, revisited according to the fundamental principles of bioethics GR Burgio and F Locatelli Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy Summary: cells. This comes as no surprise, since the ethical problems related to bone marrow transplantation (BMT) in pediatrics, The two most widely used sources of hematopoietic stem first applied successfully almost 30 years ago,1,2 have not cells for allogeneic transplants in pediatric practice are been entirely settled. It must also be emphasized that, in bone marrow (BM) and cord blood (CB). While bone children, the use of peripheral blood stem cells mobilized marrow transplantation (BMT) is reaching its 30th year through hematopoietic growth factors is not accepted rou- of application, human umbilical cord blood transplan- tinely, as the possibility of long-term adverse effects from tation (HUCBT) is approaching its 10th. Although these this practice has not yet been ruled out and it is approved procedures have basically the same purpose, a number occasionally for specific indications, such as second trans- of biological differences distinguish them. In particular, plant after a first rejection of donor marrow. the intrinsically limited quantity of CB stem cells and Although well-grounded consensus on application3–7 pre- their immunological naivete´ confer peculiar character- vails for marrow transplantation over what are now merely istics to these hematopoietic progenitors. From a bio- occasional reservations,8 it seems relevant to compare the ethical point of view, the problems which have repeat- prerogatives of the two practices (BMT and HUCBT) and edly been raised when the BM donor is a child are well- their bioethical profile in pediatrics, revisiting them as known. Different but no less important ethical problems plainly as possible in the light of the four now traditional are raised when one considers HUCBT; in this regard and basic guiding principles of bioethics, namely autonomy, the most important issues are the easier propensity of nonmaleficence, beneficence, and justice. programming a CB donor in comparison with a BM A concise review, dedicated separately to each donor (clearly due to the shorter time interval needed procedure, is basically inspired by a comparison of the two, to collect the hematopoietic progenitors); the in utero ultimately allowing an approach to their respective HLA-typing; the implication of employing ‘blood prerogatives. belonging to a neonate’ for a third party; the need to perform a number of investigations both on the CB of the donor and on the mother and the implications that Bone marrow transplantation as a traditional the discovery of disease may have for them, but also the approach for transplanting hematopoietic stem cells need to establish banks for storing CB, with the accompanying administration and management prob- As in all choices and decisions that concern the child, with lems. All these different aspects of UCBT will be dis- its intrinsic lack of autonomy or with its limitations (also cussed in the light of the four fundamental and tra- applicable to the adolescent), in BMT too any decision can ditional principles of bioethics, namely autonomy, only be validated by the informed consent of the parents nonmaleficence, beneficence and justice. (or guardians). The information made available to them Keywords: bioethics; bone marrow transplantation; cord must be as accurate and objective as possible and must blood transplantation; informed consent; cost/benefit ratio always be the groundwork for any autonomy in decision; otherwise this autonomy is not valid. Actually, there are far more serious problems for organ donations from children,9 while the usually harmless nature Since 1988, the year of its first successful application, of the harvesting of bone marrow (a tissue which regener- excellent articles have been published concerning the ates in approximately 3 weeks) still causes some reser- bioethical problems of human umbilical cord blood trans- vations,8 although not on a dramatic level. plantation (HUCBT) as a source of hematopoietic stem This finding and the potentially life-saving value of BMT are the grounds for considerations about nonmaleficence. Correspondence: Prof G Burgio, Clinica Pediatrica, Universita` di Pavia, Fundamentally, for BMT and for any medical practice bur- IRCCS Policlinico San Matteo, P le Golgi 2, I-27100 Pavia, Italy dened by bioethical doubt, it is important to revisit the Received 30 December 1996; accepted 5 March 1997 ancient concept of primum non nocere (‘do not harm’), now Bioethics of BMT and CBT in childhood GR Burgio and F Locatelli 1164 23 centuries old, as well as the need to rephrase it10 as ‘do Transplant of cord blood progenitor cells as little harm as possible’ or ‘do no harm unless that harm is necessarily associated with a compensating benefit’. This transplant, used clinically only in recent times (the If, in the risk/benefit (or cost/benefit or cost-detriment/ first use was in 1988),19,20 has now been put to the test by benefit) balance, the minimal risks affecting the donor are approximately 300 procedures. It covers areas which used compensated, according to a reasonable prediction, by sig- to be within the scope of BMT, but its bioethical profile is nificant potential benefits for the recipient-patient, as occurs significantly different. for allogeneic BMT from an HLA-compatible sibling or The placenta and the umbilical cord are temporary, short- unrelated volunteer, compliance with nonmaleficence lived structures whose physiological function is important becomes immediately evident. though limited in time. Apart from use for research (which The cost/benefit evaluation is also based on this issue. also entails careful ethical thought),21 the placenta has not The fact that compliance with beneficence is achieved been used in practice except in the last 8 years; indeed, it almost as a consequence seems indeed a corollary, at least used to be routinely disposed of at the end of the delivery. as regards the recipient-patient; but some thought has been Their temporary and disposable nature have placed the rightfully given to the role of the donor, since the existential placenta and the cord among ‘discarded tissues’: a classi- reward related to ‘having donated one’s own in order to fication which is certainly significant also from an ethical save someone’11–13 abundantly repays the donor of any viewpoint concerning the value of using these tissues,22,23 risks and costs caused by possible suffering. including the possibility of not having to obtain the ‘con- On the other hand, one cannot rule out a possible sense sent’ of the donor (of the pregnant woman and possibly of 22 of guilt as a consequence of a refusal to donate.14,15 A very her partner). young child donor may experience gratification or, vice However, this simplification has been promptly neg- 24 versa, a sense of guilt later on and include them in his or lected. Parents may make decisions as guardians for their her life experience. child and their actions should be measured in terms of the 25 Obviously, even such a globally favorable assessment of benefit of their decision to the child. Indeed, the consent BMT does not implicitly comply with the principle of jus- of the parents (especially of the mother) to use cord blood tice, since this principle involves at least evaluations con- (CB) is considered standard practice. In particular, infor- cerning the context; for example, the financial resources med consent to donate should appropriately be obtained available, which must be taken into account, especially for from the woman before she is emotionally involved in populations having a modest per capita income level. Other delivery (ie during the last 3 months of pregnancy). However, one must still ask oneself, with regard to these context-related evaluations, which might induce problems considerations, who would ever have claimed ‘ownership’ regarding justice, could also arise within the family or from of the placenta and the cord before today? Yet today the considerations related to particular circumstances. Hence, placenta has acquired immense dignity, since the hemato- for example, the intense debate in Europe and in the United poietic stem cells that its blood contains have been recog- States on the problem of transplants from a sibling con- nized as a precious ‘life-saving’ capital. Therefore, the pre- ceived with the hope of producing a compatible donor for viously mentioned question, which was irrelevant a previous child requiring BMT: ‘programming a bone mar- historically, now takes on an increasingly important sig- row donor’;16 ‘conceiving a child to save a child’;17 ‘the 18 nificance. child conceived to give life’. ‘Ownership’ of the placenta, which is well-known to Our experience with a child with chronic myelogenous 4,16 ‘belong’ to the neonate, becomes important because of the leukemia is now over 10 years old and has been extra- destination of its blood, which might be needed by another ordinarily rewarding for the family who experienced it. Of ‘recipient’ (for an allotransplant) within the family or out- course, any decision to conceive a child for the sole purpose side it, or in theory by the very child who had been nour- of making it become a bone marrow donor (or a cord blood ished by it during prenatal life, in other words by the donor) entails belittling the value of the individual to be ‘donor’, with the prospect of an autotransplant. Manage- born, viewed as a human being having a dignity of its own. ment of cord blood therefore assumes a very specific mean- However, it cannot be ignored that it is extremely difficult ing: avoiding the elimination of a ‘life-saving’ capital can to separate the reasons that lead to the conception of a child be important, to the point of raising commercial interests, solely for the joy of procreating from those linked to the with the risk of severe ethical failures.