Selecting a Favorable KIR Donor in Unrelated HCT for AML

KIR Genotyping for Unrelated Donor (URD) Selection Prior to Hematopoietic Cell Transplantation (HCT) for AML: Selecting a Favorable KIR Donor

Donors with favorable KIR B haplotype gene content have yielded reduced relapse risk and improved leukemia free survival (LFS) in retrospective analyses of unrelated donor (URD) hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML). Specifically, donors with more KIR B gene content and those who are homozygous for the centromeric (Cen) B haplotype genes (as opposed to the telomeric (Tel) genes confer the most protective effect. This study proposes to prospectively test and validate the utility and effectiveness of further informing URD identification and selection by KIR genotyping as a supplement to HLA matching and the other variables known or suspected to indicate the best URD for a patient. Hypotheses: Favorable KIR donors will improve protection against relapse and improve leukemia free survival (LFS) after URD HCT for AML. Directed study procedures for rapid KIR genotyping and reporting to searching Transplant Centers (TC) can inform donor search and selection without delay in donor availability for HCT.

Patients with acute myeloid leukemia who have received KIR genotype from an unrelated donor transplant.

To measure the impact of donor selection for KIR genotype in allogeneic URD HCT for AML on cumulative incidence of relapse. We will determine a quantitative estimate of the likelihood of better KIR donors identified with routine, non-directed donor selection along with KIR genotyping data. The observed incidence of success in a better KIR donor identified within 8 weeks will be compared to the original donor genotype expected frequencies identified in our retrospective genotyping of 1086 donors selected for AML transplants.

Inclusion Criteria: Patient with acute myeloid leukemia (AML) undergoing screening for potential URD HCT Potential URD undergoing screening to provide a HCT graft to a patient with acute myeloid leukemia (AML) at a participating institution Provides written consent Exclusion Criteria: Transplant Centers will select the best HLA matched, and as appropriate, preferred KIR donor. In situations where the preferred (best > better > neutral) KIR donor is not selected in favor of a less favorable KIR genotype donor, the center will report one or more defined reasons (donor age; gender; parity; CMV status; ABO status; availability/logistics; other) for the choice (among equivalently HLA matched donors).

Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Marsh SG, Spellman S, Haagenson MD, Saeturn K, Ladner M, Trachtenberg E, Parham P, Miller JS. Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia. J Immunol. 2014 May 15;192(10):4592-600. doi: 10.4049/jimmunol.1302517. Epub 2014 Apr 18.