Meet the Author: Dr. Antonio Jiménez Jiménez — ‘Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR’

Dr. Antonio Jiménez Jiménez is the first author of the highly-cited journal article, “Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR.” He shares in this Q&A background on how this research came about, lessons learned, and how these findings are guiding current and future initiatives.

Read on for this perspective, and then visit Transplantation and Cellular Therapy, the official journal of ASTCT, for the full article.

Nucleus: What prompted the need to revisit donor selection algorithms?

Dr. Antonio Jiménez Jiménez (AJJ): The traditional approach of prioritizing a matched sibling donor, followed by a matched unrelated donor, and only then considering alternative donors was developed largely in the calcineurin inhibitor era. Since then, better HLA typing, larger donor registries, improved supportive care, and especially post-transplant cyclophosphamide have narrowed many of the historical differences between donor types. At the same time, a prolonged search for a matched unrelated donor can delay transplant and disproportionately affect patients from underrepresented ancestry groups. Together, these changes made a more flexible and individualized donor-selection approach necessary.

Nucleus: How has post-transplant cyclophosphamide changed the role of alternative donors?

AJJ: Post-transplant cyclophosphamide has been the major driver behind improved outcomes with haploidentical and mismatched unrelated donors. Contemporary studies have shown low rates of severe acute and chronic GVHD, with survival in some analyses approaching that of matched unrelated donor transplantation. That said, this does not mean that all donor types are automatically equivalent. The donor and the GVHD prophylaxis platform need to be considered together, since the outcomes of a mismatched transplant depend heavily on the regimen used.

Nucleus: Which factors beyond HLA matching should clinicians prioritize?

AJJ: Donor age is one of the most consistently validated non-HLA factors, and younger donors should generally be prioritized when appropriate. Donor-specific antibodies should also be assessed early so that targeted donors can be excluded before significant time is invested in the search. Other relevant considerations include possible germline predisposition variants in related donors, donor-recipient size difference, donor availability, and how quickly the graft can be secured. Factors such as sex, parity, CMV status, and ABO may still matter in selected situations, but they should not outweigh stronger factors such as HLA compatibility, donor age, and the absence of DSAs.

Nucleus: How should centers balance HLA matching against the urgency of transplantation?

AJJ: HLA matching remains important, but donor searches should no longer be strictly sequential. If a patient has a high likelihood of identifying a suitable matched unrelated donor, that search can proceed while alternative donors are evaluated in parallel when timing is a concern. BMT CTN 1702 showed that patients with a very low likelihood of finding a matched unrelated donor could move directly to an alternative donor strategy without compromising survival. This approach helps avoid unnecessary delays and may improve access to transplant, particularly for patients from ancestry groups that are less represented in donor registries.

Nucleus: When might an alternative donor be equivalent or preferable?

AJJ: An alternative donor may be the better early option when the likelihood of finding a matched unrelated donor is low, when donor procurement would delay an urgent transplant, or when available related donors carry a shared germline predisposition variant. In selected patients receiving PTCy, a younger mismatched unrelated donor may also be preferable to a substantially older matched donor, although this still requires individualized judgment and further validation. These strategies are especially relevant for patients of non-European ancestry, who are less likely to identify a fully matched unrelated donor. 

Nucleus: What are the most important unanswered questions?

AJJ: We still need a better understanding of how completely PTCy overcomes the HLA barrier and whether certain mismatches can be selected to preserve graft-versus-tumor effects without adding toxicity. More work is also needed to determine whether GVHD prophylaxis should be tailored to donor type and whether traditional donor factors such as sex, parity, CMV status, and ABO compatibility remain important in the PTCy era. Pediatric patients and patients undergoing transplant for nonmalignant diseases remain particularly understudied.