Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis

Minimal residual disease prior to allogeneic hematopoietic cell transplantation has been associated with increased risk of relapse and death in patients with acute myeloid leukemia, but detection methodologies and results vary widely. We performed a systematic review and meta-analysis evaluating the prognostic role of minimal residual disease detected by polymerase chain reaction or multiparametric flow cytometry before transplant. We identified 19 articles published between January 2005 and June 2016 and extracted hazard ratios for leukemia-free survival, overall survival, and cumulative incidences of relapse and non-relapse mortality. Pre-transplant minimal residual disease was associated with worse leukemia-free survival (HR=2.76 [1.90-4.00]), overall survival (HR=2.36 [1.73-3.22]), and cumulative incidence of relapse (HR=3.65 [2.53-5.27]), but not non-relapse mortality (HR=1.12 [0.81-1.55]). These associations held regardless of detection method, conditioning intensity, and patient age. Adverse cytogenetics was not an independent risk factor for death or relapse. There was more heterogeneity among studies using flow cytometry-based than WT1 polymerase chain reaction-based detection (I(2)=75.1% vs. <0.1% for leukemia-free survival, 67.8% vs. <0.1% for overall survival, and 22.1% vs. <0.1% for cumulative incidence of relapse). These results demonstrate a strong relationship between pre-transplant minimal residual disease and post-transplant relapse and survival. Outcome heterogeneity among studies using flow-based methods may underscore site-specific methodological differences or differences in test performance and interpretation

Significant Improvements in the Practice Patterns of Adult Related Donor Care in US Transplantation Centers

Recent investigations have found a higher incidence of adverse events associated with hematopoietic cell donation in related donors (RDs) who have morbidities that if present in an unrelated donor (UD) would preclude donation. In the UD setting, regulatory standards ensure independent assessment of donors, one of several crucial measures to safeguard donor health and safety. A survey conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR) Donor Health and Safety Working Committee in 2007 reported a potential conflict of interest in >70% US centers, where physicians had simultaneous responsibility for RDs and their recipients. Consequently, several international organizations have endeavored to improve practice through regulations and consensus recommendations. We hypothesized that the changes in the 2012 FACT-JACIE Standards, resulting from the CIBMTR study, will have significantly impacted practice. Accordingly, a follow-up survey of US transplant centers was conducted to assess practice changes since 2007, and investigate additional areas where RD care was predicted to differ from UD care. 73 centers (53%), performing 79% of US RD transplants responded. Significant improvements were observed since the earlier survey; 62% centers now ensure separation of RD and recipient care (P<0.0001). However, this study identifies several areas where RD management does not meet international donor care standards. Particular concerns include counseling and assessment of donors before HLA typing, with 61% centers first disclosing donor HLA results to an individual other than the donor, the use of unlicensed mobilization agents, and the absence of long-term donor follow-up. Recommendations for improvement are described

How do we forecast tomorrow's transfusion:The future of hematopoietic stem cell donation

Over the past three decades, the field of stem cell research and development (R&D) has witnessed extraordinary progress, allowing us to envisage a future where cell therapies can be used for the treatment of diseases currently considered incurable. Contemplating such a future also requires reflecting on donors and exploring their readiness to donate hematopoietic stem cells (HSCs) for these purposes. In 2019, seven focus groups took place with members of the public, prospective donors, and donors as part of a project launched by Anthony Nolan (AN), a UK not-for-profit organization and stem cell donor registry. The aim of the project was to assess prospective donors’ and donors’ attitudes towards donating cells for novel treatments R&D. Participants were asked about their donation being used for the treatment of multiple recipients and quality-of-life (QoL) conditions. Some participants viewed donating for multiple recipients as beneficial and could act as a “pull factor” to encourage more donors. Others were keen to position the idea of helping multiple recipients as an “added bonus”. Some expressed worry that such donations might diminish the connection between donors and recipients and drew upon the influential power of “success stories” to encourage and motivate future donors. Most participants considered it acceptable to donate HSCs for QoL conditions. A hierarchy of illnesses formed during the focus groups, as some donors were concerned they might be asked to donate stem cells to enhance and improve the lives of ‘healthy’ people. Responses suggest that the donor-recipient relationship plays a significant role in influencing donation decisions, and that underlying the portrayal of this relationship is a power dynamic. Donors’ agreeableness to donate for QoL conditions is crucial to expand our understanding of stem cell-based therapies. Nevertheless, we must also consider how such donations might impact donor recruitment for transplant patients

Exploring the perceived benefits of ethics education for laboratory professionals

Background: Clinical laboratories face ethical challenges on a daily basis. The ethics training provided for clinical laboratory staff is variable, with some receiving no training. We aimed to explore the perceived benefits of ethics education for laboratory professionals. Methods: Ethics training was provided to approximately 60 laboratory professionals in a UK not-for-profit blood cancer organisation, with group discussions incorporated into the session. The session covered dominant ethical theories and principles, the defining moments in medical research ethics and the ethical aspects of laboratory practices. At the end of the session a short optional paper survey was distributed to the participants to obtain feedback on the training. The feedback was anonymous and thematically coded. Results: Attendees reported to be more aware of the existence and importance of ‘everyday’ ethics in their workplace. Responses also showed that the training session had provided participants with an opportunity for ethical reflection in themselves and in discussion with their colleagues. Conclusions: Despite clinical laboratory professionals being faced with ethical challenges daily, there is comparatively little ethics education provided. Ethics training is believed to improve the ethical attitude of laboratory staff and help them when making decisions in their work. We have shown that ethics education is important for laboratory professionals to develop and retain ethical awareness, and ethical reflection. By gaining insight into the ethical aspects of their practices, laboratory professionals can apply this understanding when faced with making challenging decisions in their workplace, in order to act in the best interests of their patients

Prospective donors’ perspectives on hematopoietic cell donation for cell and gene therapy research and development

Aims: To explore prospective donors’ attitudes and perceptions towards donating hematopoietic stem cells (HSCs) for novel treatments research and development (R&D). Methods: A survey was launched by Anthony Nolan (AN) to assess prospective donors’ willingness to donate HSCs for novel therapies R&D, and their degree of comfort with the AN collaborating with and receiving payment from external organizations. Results: Most participants (87%) were willing to donate for novel treatment R&D and were comfortable with AN collaborating with external organizations and receiving payment (91% and 80%, respectively). Conclusion: Results reveal an overall positive response towards donating HSCs for R&D. These findings can support stakeholders and policymakers in outlining donation practices that uphold donors’ safety and welfare