KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation

Daniel Weisdorf, Sarah Cooley, Tao Wang, Elizabeth Trachtenberg, Cynthia Vierra-Green, Stephen Spellman, Jennifer A. Sees, Ashley Spahn, Jenny Vogel, Todd A. Fehniger, Ann E. Woolfrey, Steven M. Devine, Maureen Ross, Edmund K. Waller, Ronald M. Sobecks, Joseph McGuirk, Betul Oran, Sherif S. Farag, Tsiporah Shore, Koen Van BesienSteven G.E. Marsh, Lisbeth A. Guethlein, Peter Parham, Jeffrey S. Miller

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Natural killer (NK) cell recognition and killing of target cells are enhanced when inhibitory killer immunoglobulin-like receptors (KIR) are unable to engage their cognate HLA class I ligands. The genes of the KIR locus are organized into either KIR B haplotypes, containing 1 or more activating KIR genes or KIR A haplotypes, which lack those genes. Analysis of unrelated donor (URD) hematopoietic cell transplants (HCT), given to acute myeloid leukemia (AML) patients between 1988 and 2009, showed that KIR B haplotype donors were associated with better outcomes, primarily from relapse protection. Most of these transplants involved marrow grafts, fully myeloablative (MAC) preparative regimens, and significant HLA mismatch. Because the practice of HCT continues to evolve, with increasing use of reduced intensity conditioning (RIC), peripheral blood stem cell grafts, and better HLA match, we evaluated the impact of URD KIR genotype on HCT outcome for AML in the modern era (2010-2016). This analysis combined data from a prospective trial testing URD selection based on KIR genotypes (n 5 243) with that from a larger contemporaneous cohort of transplants (n 5 2419). We found that KIR B haplotype donors conferred a significantly reduced risk of leukemia relapse and improved disease-free survival after RIC, but not MAC HCT. All genes defining KIR B haplotypes were associated with relapse protection, which was significant only in transplant recipients expressing the C1 epitope of HLA-C. In the context of current HCT practice using RIC, selection of KIR B donors could reduce relapse and improve overall outcome for AML patients receiving an allogeneic HCT.

Original languageEnglish
Pages (from-to)740-754
Number of pages15
JournalBlood Advances
Volume4
Issue number4
DOIs
StatePublished - Feb 25 2020

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    Weisdorf, D., Cooley, S., Wang, T., Trachtenberg, E., Vierra-Green, C., Spellman, S., A. Sees, J., Spahn, A., Vogel, J., Fehniger, T. A., Woolfrey, A. E., Devine, S. M., Ross, M., Waller, E. K., Sobecks, R. M., McGuirk, J., Oran, B., Farag, S. S., Shore, T., ... Miller, J. S. (2020). KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation. Blood Advances, 4(4), 740-754. https://doi.org/10.1182/bloodadvances.2019001053