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WMDA recommendations on genetic testing post-HCT and the implications of findings for donors

Feb 2024

The World Marrow Donor Association (WMDA) has established guidelines on genetic testing after allogeneic hematopoietic cell transplant (alloHCT). The study explores the implications of post-transplant genetic testing, specifically focusing on the detection of genetic and molecular abnormalities potentially originating from donors. This research is critical due to the growing routine use of extensive genetic testing post-transplant, raising challenges in distinguishing the origins and significance of detected variants and necessitating guidelines for consent, testing, and donor notification to maintain donor safety and autonomy.

Download a PDF of the study highlights and citation here.

Background

The increasing detection of genetic variants in post-transplant recipients poses a challenge, whether they are disease-causing or incidental findings. These variants might originate from the donor or arise de novo in donor cells post-engraftment. Certain germline variants are known to elevate the risk of hematologic malignancies and other cancers. However, there is limited guidance on managing these findings, which can have significant implications for donor health.

A recent scoping review revealed a lack of consensus recommendations for donor follow-up, testing, interpretation, and disclosure of genetic findings. This study aimed to establish guidelines for handling genetic findings of potential donor origin, providing a framework for decision-making and donor communication.

Methods

The research was conducted by the Medical Working Group of the WMDA, which brought together a group of international experts to develop these guidelines. The guidelines focus on volunteer unrelated donors who have donated bone marrow, peripheral blood stem cells, or mononuclear cells for patients undergoing alloHCT. Although some information may apply to related donors and other contexts, these are beyond the scope of the current guidelines.

Results

Key recommendations are noted in the paper and in the Figure below. Routine genetic screening of all unrelated stem cell donors before donation is not recommended. Post-donation testing should be performed only when necessary, avoiding undirected blanket testing. Transplant centers should be mindful of the implications for donors and follow a structured process for reporting and handling findings. Use the term "donor-derived" only after confirmation through appropriate testing; otherwise, use "genetic findings of potential donor origin." The paper outlines the following step-by-step guidelines:

  • Evaluate Test Validity and Likelihood: Ensure registries receive necessary information from transplant centers to determine if an abnormality is donor-derived.
  • Clinical Significance and Actionability: Assess if findings are clinically significant or actionable.
  • Ethical and Legal Considerations: Ensure donors are informed about potential post-transplant genetic testing.
  • Genetic Counseling and Testing Referral: Provide recommendations for counseling and referrals.
  • Follow-Up Considerations: Establish follow-up protocols.
  • Sharing Practice Recommendations: Promote consistent practice recommendations.

Key Takeaways

The growing prevalence and complexity of post-transplant genetic testing underscore the need for robust guidelines and processes for consenting and disclosing findings. These guidelines support registries and transplant centers in ensuring safe and effective transplants while protecting donor health and rights. These findings emphasize the importance of donor safety and ethical considerations in genetic testing and transplantation processes.

The WMDA and NMDP play vital roles in providing life-saving cells while ensuring the care and safety of both recipients and donors. NMDP has developed and implemented a thorough process for consenting and reporting genetic findings of potential donor origin aligned to these guidelines to support donors through this process. These guidelines offer critical recommendations for managing genetic findings of potential donor origin, protecting donor health and rights, and supporting effective transplantation practices.

Figure

This figure displays the recommended process for variant classification, donor disclosure, and genetic counseling as needed.

This figure displays the recommended process for variant classification, donor disclosure, and genetic counseling as needed
Pryce A, et al., published in Transplantation and Cellular Therapy