World Marrow Donor Association

Timing of allogeneic hematopoietic cell transplantation (HCT) is a crucial factor that can significantly impact transplant outcome with delay potentially leading to disease progression or patient condition deterioration. While availability of unrelated donors is a key performance indicator of the World Marrow Donor Association (WMDA), registries often struggle to meet benchmark thresholds established to ensure that patients have timely access to transplant. At workup (WU), if the donor is unable to proceed due to unanticipated personal or medical reasons, the impact to patient care can be catastrophic; the transplant centre (TC) must urgently identify another suitable candidate for donation whose requisite testing and preparation can significantly extend the timeline to transplant. In 2024, global organisations indicated that 16% of all WU were canceled due to donor-related reasons, although unavailability rates varied substantially between participating registries. Despite initial rebound post-pandemic, donor unavailability at WU has increased steadily since 2021, now exceeding that experienced at the height of the pandemic in 2020 where it peaked at 15.2%.2 These findings underscore the need for patient registries and TC to define backup donor (BUD) strategies to mitigate patient risk. However, differences in national practices have resulted in variability in the search strategies, policies, and procedures currently used by organisations to ensure that various donor and treatment options are available for patients to minimise the risk of delayed transplant if a primary donor becomes unavailable. Reciprocally, these inconsistencies, combined with insufficient TC communication, can cause confusion for donor registries and donor centers (DC), potentially resulting in misinformed donors, unnecessary WU and/or product collection, and increased resource burden. The WMDA believes it is imperative that both donor and patient registries define policies for the proactive identification and management of BUD to minimise patient risk and to increase transparency and safety for BUD. Management of BUD at WU is a complex issue in which patient access to timely transplant must be balanced with the impact on prospective donors, DC and collection centre (CC) resources, and potential costs incurred by TC and their respective registries. Lack of standardisation in practice, including the definition of a BUD, has prompted the WMDA to provide the following guidance toward BUD policy and introduce a common language for describing BUD activities and emerging practices in donor management. We encourage organisations to define their policy in observation of the recommendations set forward herein.

Manufacturing cell and gene therapy (CGT) products derived from donor cells may involve genetic and other testing that identifies unexpected findings of potential donor origin. Testing may be done to assess the safety of the product or manufacturing process and to assess gene transduction efficiency or aspects of cell expansion, and also may be performed in recipients of CGT products following infusion to monitor the effects of treatment. Tests that may identify unexpected findings in donor cells include chromosomal karyotyping, targeted tests for specific gene mutations or rearrangements, and large gene panels or whole genome sequencing to detect mutations or cytogenetic abnormalities of relevance to donors. Deciphering whether variants are of donor origin as opposed to introduced via manufacturing processes is key, as is having a framework for protecting donors that includes procedures for ensuring robust donor consent and appropriate pathways for disclosure of clinically relevant and actionable results. Building on recent recommendations from the World Marrow Donor Association regarding unexpected findings of potential donor origin following allogeneic hematopoietic cell transplantation, an expert group was assembled to review available evidence and develop a framework to apply to healthy volunteer donors who provide cells for the manufacturing of allogeneic CGT products. These guidelines aim to provide recommendations for predonation consenting, as well as a framework for informing and managing the care of donors when findings of potential donor origin are identified. Since many cellular therapies remain under development, donors who provide cells for any aspect of research and development of CGT products require special consideration. Realizing that cellular therapy may involve commercial entities and donors that are recruited within conventional stem cell registries or through other mechanisms, we provide suggestions on how recommendations can be adapted.

The cell and gene therapy (CGT) sector has witnessed significant advancement over the past decade, the inception of advanced therapy medicinal products (ATMPs) being one of the most transformational. ATMPs treat serious medical conditions, in some cases providing curative therapy for seriously ill patients. There is interest in pivoting the ATMP development from autologous based treatments to allogenic, to offer faster and greater patient access that should ultimately reduce treatment costs. Consequently, starting material from allogenic donors is required, igniting ethical issues associated with financial gains and donor remuneration within CGT. The World Marrow Donor Association (WMDA) established the Cellular Therapy Committee to identify the role WMDA can play in safeguarding donors and patients in the CGT field. Here we review key ethical principles in relation to donating cellular material for the CGT field. We present the updated statement from WMDA on donor remuneration, which supports non-remuneration as the best way to ensure the safety and well-being of donors and patients alike. This is in line with the fundamental objective of the WMDA to maintain the health and safety of volunteer donors while ensuring high-quality stem cell products are available for all patients. We acknowledge that the CGT field is evolving at a rapid pace and there will be a need to review this position as new practices and applications come to pass.