Author ORCID Identifier

https://orcid.org/0000-0002-8728-3327

Document Type

Basic Science Research

Date of Poster

2020

Date of Submission

June 2020

Abstract

Introduction/Background

Hematopoietic cell transplantation (HCT) provides

a cure for patients with acute myeloid leukemia.

Natural killer cells (NK) play an important role

in graft versus leukemia (GVL) effect after HCT,

through killer immunoglobulin-like receptor (KIR)

interaction with HLA ligands. This study is

undertaken to validate our previously published

mathematical model accounting for the KIR-KIRL

interactions in a post HCT setting.

Methods

Retrospective data were obtained from the Center

for International Blood and Marrow Transplant

Registry for 2317 donor recipient pairs (DRP) who

underwent 7/8 or 8/8 HLA allelic matched

unrelated donor (URD) HCT for AML. KIR-HLA

interaction scores were calculated by summing

interaction values as previously described

(Krieger et. Al BBMT 2019).

Results

Relapse risk was significantly reduced with

donor-recipient pairs (DRP) with the higher

inhibitory KIR-KIRL interaction and missing KIRL

scores, Cox prop hazard, HR=0.86 (P=0.01) &

HR=0.84 (P=0.02) respectively. The inhibitory

KIR-KIRL interaction score components were then

summed to give an IM-KIR score; IM KIR score =5

was also associated with a lower relapse risk, HR

0.8 (P=0.003). Subset analysis of 8/8 HLA

matched patients showed further relapse

reduction HR 0.75 (P=0.001); those patients with

IM-KIR=5 donors who received ATG for in vivo T

cell depletion (N=730) showed a 39% relapse

reduction (HR 0.61, P=0.001) with a trend toward

improved RFS, HR 0.84 (p=0.11). The use of ATG

was shown to modify the effect of IM KIR score in

interaction analysis (p=0.049), suggesting higher

NK cell magnitude of KIR-KIRL interaction

compensates for the general increase of relapse

who receive in vivo T cell depletion.

Conclusion

This large international study confirms that

unrelated DRPs with high iKIR and mKIR scores, as

well as a combined IM-KIR scores confer

significant relapse protection after MUD HCT,

indicating that donors with a higher iKIR content

may be considered optimal for URD HCT recipients

with AML.

Rights

© The Author

Is Part Of

VCU School of Medicine GME Resident and Fellow Research Day Posters

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