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.

Abstract

Killer cell Ig-like receptors (KIRs) interact with HLA class I ligands to regulate NK cell development and function. These interactions affect the outcome of unrelated donor hematopoietic cell transplantation (HCT). We have shown previously that donors with KIR B versus KIR A haplotypes improve the clinical outcome for patients with acute myelogenous leukemia by reducing the incidence of leukemic relapse and improving leukemia-free survival (LFS). Both centromeric and telomeric KIR B genes contribute to the effect, but the centromeric genes are dominant. They include the genes encoding inhibitory KIRs that are specific for the C1 and C2 epitopes of HLA-C. We used an expanded cohort of 1532 T cell-replete transplants to examine the interaction between donor KIR B genes and recipient class I HLA KIR ligands. The relapse protection associated with donor KIR B is enhanced in recipients who have one or two C1-bearing HLA-C allotypes, compared with C2 homozygous recipients, with no effect due to donor HLA. The protective interaction between donors with two or more, versus none or one, KIR B motifs and recipient C1 was specific to transplants with class I mismatch at HLA-C (RR of leukemia-free survival, 0.57 [0.40-0.79]; p = 0.001) irrespective of the KIR ligand mismatch status of the transplant. The survival advantage and relapse protection in C1/x recipients compared with C2/C2 recipients was similar irrespective of the particular donor KIR B genes. Understanding the interactions between donor KIR and recipient HLA class I can be used to inform donor selection to improve outcome of unrelated donor hematopoietic cell transplantation for acute myelogenous leukemia.

• Authors: Sarah Cooley, Daniel J Weisdorf, Lisbeth A Guethlein, John P Klein, Tao Wang, Steven G E Marsh, Stephen Spellman, Michael D Haagenson, Koy Saeturn, Martha Ladner, Elizabeth Trachtenberg, Peter Parham, Jeffrey S Miller
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 192 Issue 10 Pg. 4592-600 (May 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 24748496 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• HLA-C Antigens
• Receptors, KIR

Topics

• Allografts
• Disease-Free Survival
• Female
• HLA-C Antigens (genetics, immunology)
• Haplotypes (immunology)
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia, Myeloid, Acute (genetics, immunology, mortality, therapy)
• Male
• Receptors, KIR (genetics, immunology)
• Retrospective Studies
• Survival Rate
• Unrelated Donors