KIR Donor Selection: Feasibility in Identifying better Donors.

Area of Science:

• Immunogenetics
• Hematology
• Transplantation Immunology

Background:

• Previous research indicated that acute myelogenous leukemia (AML) transplants utilizing killer cell immunoglobulin-type receptor (KIR) B haplotype better or best unrelated donors (URDs) are associated with reduced relapse rates and improved survival.
• The clinical utility of KIR genotyping in donor selection for AML remains an area of active investigation, necessitating prospective evaluation.

Purpose of the Study:

• To prospectively evaluate the effectiveness of centralized donor KIR genotyping in selecting optimal donors for acute myelogenous leukemia (AML) searches.
• To determine the impact of KIR genotyping on donor selection success rates and transplantation timelines.
• To assess the feasibility of incorporating KIR genotyping into routine donor selection protocols.

Main Methods:

• Conducted a prospective trial involving 535 AML searches across 14 centers, with centralized donor KIR genotyping for donor selection.
• Collected data on the number of donors requested for KIR genotyping per search and the time to report KIR genotype results.
• Analyzed the proportion of KIR better or best donors identified and the impact of KIR genotyping on the time from search to transplant.

Main Results:

• A mean of 30% of KIR better or best donors were identified across the participating centers.
• Increasing the number of donors requested for KIR genotyping per search significantly improved the likelihood of identifying KIR better or best haplotype donors.
• KIR genotyping did not delay transplantation; the time from search to transplant was identical for KIR-genotyped and non-KIR-genotyped donors.

Conclusions:

• Prospective KIR genotyping can rapidly identify favorable genotype donors for AML transplantation.
• Selecting a greater number of donors for KIR genotyping per search substantially increases the probability of finding KIR best or better donors.
• Transplant centers and donor registries should collaborate to integrate KIR genotyping and other genetic factors into donor selection protocols beyond HLA, age, and parity.