First do no harm

Can a physician caring for a patient who requires a transplant make an unbiased assessment of the suitability of that patient's relative to be the donor? In this issue of Blood, O'Donnell et al highlight this important question in their article reporting practice patterns for related donor care in the United States.¹ 

A real or potential conflict of interest exists when a transplant recipient and the intended donor are assessed by the same physician. This is important as trust among physician, donor, and/or patient could break down, and there is a possibility that medical and psychosocial risks to the donor may be underplayed or not objectively considered.

Both in solid organ transplantation and in unrelated donor hematopoietic cell transplantation (HCT), regulations state that the donor must be (medically) assessed by a physician who is not a member of the team caring for the recipient.^2,3  Conversely, regulations concerning related donors of hematopoietic stem cells (HSC) are sparse. Although the Foundation for the Accreditation of Cellular Therapy and the Joint Accreditation Committee of International Society for Cellular Therapy and European Group for Blood and Marrow Transplantation (FACT-JACIE) recommends that “an independent physician be utilized for evaluating donor suitability” for all donors, it does not have an explicit standard addressing all aspects of related donor management.⁴ 

In view of this absence of clear regulations for related donors, O'Donnell et al hypothesized that overlapping care teams may be a common practice. To address this, they performed a large survey of transplantation centers in the United States to assess practice patterns for evaluation and care of related donors.

The survey addresses 2 main questions: what type of health care provider is involved in the medical clearance, informed consent, and medical management of the related donor, and what is the relationship of that provider to the transplant recipient. The survey was sent to 222 transplantation teams with an overall response rate of 40%. Importantly, the majority of centers that did respond were FACT-accredited. In almost all cases (> 80%), a transplant physician performed the medical care and consent. The key finding in this study confirms the hypothesis, as more than 70% of centers replied that the same physician caring for the donor had (or might have) simultaneous responsibility for the care of the recipient. Interestingly, the larger the transplant, the less likely that the donor's and recipient's physicians would be the same—which may be as a result of staffing issues in smaller centers and the emphasis on the transplantation expertise in assessing the donors. Clare et al report very similar findings in a survey of practice patterns in related donor care in Europe.⁵  More than half of the donors were consented by the transplant physician and in only a quarter of centers was donor assessment performed by a physician not connected to the transplantation team.

Is it necessary that a transplant physician do the donor assessment? Non–transplant providers could easily be trained to understand relevant transplantation and donation issues. Independent assessors or advocates who may be geographically separate, and possibly part of a network associated with nearby centers, could be used. The need for an independent advocate may be especially important in the case of pediatric donors, where there may be an inherent conflict of interest be-cause of the requirement for a consenting parent/guardian.

This report is timely, especially with regard to pediatric donors. The American Academy of Pediatrics has this year published a policy statement for children as (related) hematopoietic cell donors in which it states that a donor advocate should be appointed and that the advocate must be independent of the team responsible for the direct care of the recipient.⁶  The requirement for an independent accredited assessor (guardian/advocate) distinct from the recipient's care team is already entrenched in European Union law (Tissues and Cells Directive 2004/23/EC; http://www.dh.gov.uk/en/Publichealth/Scientificdevelopmentgeneticsandbioethics/Tissue/Tissuegeneralinformation/DH_4136920. Accessed May 5, 2010).

There is strong justification for bringing related HCT donor care in line with that of unrelated donors and addressing additional issues, such as adverse events reporting and donor follow-up. Van Walraven et al⁷  on behalf of the World Marrow Donor Association, which regulates all aspects of unrelated HCT donor care and management,³  have recently published recommendations in this regard.

We need to recognize, however, that there are obvious differences between related and unrelated donors—for example, age and ethical and psychosocial concerns. The psychosocial risks and benefits to the donor are important and data in related donors are very limited and/or relatively outdated. The assumption that a related donor should be, or is, willing to accept a greater degree of risk in view of the his or her potential emotional benefit of helping a sick relative is unsubstantiated and controversial. In addition, it is not clear whether related donors feel that long-term follow-up is desirable, particularly if the donor's relative has died. Some European countries already have a legal requirement to perform regular follow-up of related donors, similar to that in unrelated donors. It is hoped that an ambitious study currently recruiting in the United States—RDSafe (related donor safety study): a Multi-Institutional Study of HSC Donor Safety and Quality Life by Pulsipher and Switzer (http://www.researchgrantdatabase.com/g/1R01HL085707) will answer some of these questions by comparing medical and psychological toxicities of related HSC donors with unrelated donors.

To conclude, the current widespread international practice of overlapping recipient and donor care teams raises serious concerns about possible conflicts of interest. O'Donnell et al, and others, highlight the lack of clear guidelines for related donors and strongly encourage existing regulatory frameworks to develop explicit standards to ensure uniformity of care. It behooves us as a transplantation community to protect and serve the needs of HCT recipients and their donors.