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