Allogeneic Hematopoietic Cell Donor Selection: Contemporary Guidelines from the NMDP/CIBMTR

Abstract

Allogeneic hematopoietic cell transplantation (HCT) remains a curative therapy for many patients with hematologic malignancies, bone marrow failure syndromes, inborn errors of immunity and metabolic disorders. Current donor selection strategies typically prioritize the selection of an HLA-matched donor over HLA mismatched ("alternative") donor sources, with a hierarchical approach to the donor search. More recent data challenge this rubric, particularly in the context of novel graft-versus-host disease (GVHD) prophylaxis strategies that demonstrate improved outcomes in alternative donor HCT recipients. In this setting, an increased emphasis on non-HLA factors (both donor characteristics and systemic factors) in determining donor selection is now feasible. In this guideline, we review recent evidence from prospective clinical trials as well as high-quality observational studies and provide expert panel recommendations on donor selection algorithms and prioritization in the era of novel GVHD prophylaxis. We then highlight important questions still to be answered in our field.

Keywords: Allogeneic; Donor selection; Guidelines; Search strategy; Transplantation.

Figure 1:

Trends in donor use (Panel A) demonstrate increasing use of HLA matched unrelated donors, haplo grafts, and more recently, HLA-mismatched unrelated donors. Differences in HLA haplotype diversity across global populations drives disparity in access to HLA matched unrelated donors (Panel B). Consideration of HLA mismatched donors, including more highly mismatched donors (<7/8 matched), improves access in racial/ethnically diverse populations.

Figure 2:

Search for an allogeneic HCT donor may proceed using a sequential (left), or concurrent (right) search strategy. In a concurrent search strategy, a search prognosis tool is used to determine the likelihood of an available HLA matched unrelated donor. Patients with a search prognosis score indicating there is a low likelihood that an HLA matched donor exists should undergo a search for alternative donors concurrent with sibling donor HLA typing.