Ethics of using a bone marrow donor with Klinefelter syndrome.

For many patients who require an allogeneic stem cell transplant, a human leukocyte antigen (HLA)-matched sibling or an appropriate unrelated donor can be identified. However, there are some pediatric patients who require transplantation for whom the best outcome and/or the only option is the collection of umbilical cord blood following the birth of an HLA identical sibling. This scenario occurs most often in children from ethnic minority groups for whom banked samples are scarce and in patients affected with certain genetic disorders, such as the immune deficiency diseases. In the latter situation, preimplantation or prenatal genetic testing for the specific disorder and HLA typing can ensure that the pregnancy will result in an unaffectedmatched donor for the affected sibling. Indeed, over the past decade advances in preimplantation technology have allowed the reliable determination of HLA tissue matching and the status of the embryo with regard to the specific genetic disease. These advances permit families with a child in need of a stem cell transplant to conceive and deliver an HLAmatched donor for their existing child. This approach has generated substantial controversy among ethicists, the medical community, and the public. Some of the attention surrounding these situations has focused on concerns about the genuine desire of the family to have another child and the psychological impact on the donor conceived specifically for purpose of saving the sick child. Despite this attention, this approach continues to be used and programs for the creation of stem cell donors for children with non-malignant diseases in need of stem cell transplantation have arisen. In the article by Balsi et al. (1) in this issue, a three-yr-old boy with Wiskott–Aldrich syndrome (WAS) received HLA identical bone marrow and cord blood stem cells stored at birth from an 11month-old brother who was prenatally identified as unaffected with WAS. The authors do not state whether or not the brother was specifically conceived for the purposes of being a donor for the older brother but do note that the pregnancy had not been terminated after the prenatal identification of Klinefelter syndrome as the parents wanted to provide a donor for the other son who had no other transplant option. Thus, it would appear that the family elected to continue a pregnancy that they may have otherwise terminated based on the fact that the fetus was an HLA identical match and was unaffected with WAS. Klinefelter syndrome is a chromosomal abnormality that is most commonly due to a nondysjunction event that results in a 47, XXY karyotype. During childhood boys with Klinefelter syndrome may have learning disabilities and difficulty with speech and language development. At puberty, male sexual development does not occur normally and affected men typically have low levels of testosterone, gynecomastia, reduced facial and body hair, and primary infertility. Men with Klinefelter syndrome also have an increased risk of developing breast cancer and there have also been reports linking Klinefelter syndrome with an increased risk for hematologic malignancies. Balsi et al. comment that they had a discussion about the ethics of using a Klinefelter syndrome donor due to the theoretical risk of a hematologic malignancy arising in the recipient. Notably they did not address the ethical issue related to the parents’ decision not to terminate the Klinefelter syndrome pregnancy due their desire to provide a donor for the affected son. In reality the parents of the child with WAS had a very difficult choice to make. They could try to create another HLAmatched child to be a stem cell donor and possibly rescue their dying son from his fate. They could also accept the fact their son would die from the disease and try to have another child Pediatr Transplantation 2008: 12: 496–498 Copyright 2008 Blackwell Munksgaard