PMID- 34234295
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20220423
IS  - 1476-5365 (Electronic)
IS  - 0268-3369 (Linking)
VI  - 56
IP  - 11
DP  - 2021 Nov
TI  - Increased donor inhibitory KIR with known HLA interactions provide protection 
      from relapse following HLA matched unrelated donor HCT for AML.
PG  - 2714-2722
LID - 10.1038/s41409-021-01393-9 [doi]
AB  - Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play 
      an important role in natural killer cell-mediated graft versus leukemia effect 
      (GVL) after hematopoietic cell transplant (HCT) for AML. Accounting for known 
      KIR-KIRL interactions may identify donors with optimal NK cell-mediated 
      alloreactivity and GVL. A retrospective study of 2359 donor-recipient pairs (DRP) 
      who underwent unrelated donor (URD) HCT for AML was performed. KIR-KIRL 
      combinations were determined and associations with clinical outcomes examined. 
      Relapse risk was reduced in DRP with both higher inhibitory KIR-KIRL (iKIR) and 
      missing KIRL (mKIR) scores, with HR 0.86 (P = 0.01) & HR 0.84 (P = 0.02) 
      respectively. The iKIR and mKIR score components were summed to give a maximal 
      inhibitory KIR ligand (IM-KIR) score for each donor, which if it was 5, as 
      opposed to <5, was also associated with a lower relapse risk, SHR 0.8 
      (P = 0.004). All IM = 5 donors possess KIR Haplotype B/x. Transplant-related 
      mortality was increased among those with IM-KIR = 5, HR, 1.32 (P = 0.01). In a 
      subset analysis of those transplanted with 8/8 HLA-matched DRP, anti-thymocyte 
      globulin recipients with IM-KIR = 5, had a lower relapse rate HR, 0.61 
      (p = 0.001). This study demonstrates that HLA-matched unrelated donors with the 
      highest inhibitory KIR content confer relapse protection, albeit with increased 
      TRM. These donors all have KIR haplotype B. Clinical trials utilizing donors with 
      a higher iKIR content in conjunction with novel strategies to reduce TRM should 
      be considered for URD HCT in recipients with AML to optimize clinical outcomes.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Krieger, Elizabeth
AU  - Krieger E
AD  - Department of Pediatrics, Virginia Commonwealth University, Richmond, VA, USA.
FAU - Qayyum, Rehan
AU  - Qayyum R
AUID- ORCID: 0000-0003-3086-8014
AD  - Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, 
      USA.
FAU - Keating, Armand
AU  - Keating A
AD  - Princess Margaret Cancer Centre, Toronto, ON, Canada.
FAU - Toor, Amir
AU  - Toor A
AUID- ORCID: 0000-0001-5317-8433
AD  - Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 
      USA. amir.toor@vcuhealth.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20210707
PL  - England
TA  - Bone Marrow Transplant
JT  - Bone marrow transplantation
JID - 8702459
RN  - 0 (Receptors, KIR)
SB  - IM
EIN - Bone Marrow Transplant. 2021 Oct 15;:. PMID: 34654887
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - *Leukemia, Myeloid, Acute/therapy
MH  - Receptors, KIR
MH  - Recurrence
MH  - Retrospective Studies
MH  - Unrelated Donors
EDAT- 2021/07/09 06:00
MHDA- 2022/03/11 06:00
CRDT- 2021/07/08 06:31
PHST- 2020/12/22 00:00 [received]
PHST- 2021/06/23 00:00 [accepted]
PHST- 2021/06/14 00:00 [revised]
PHST- 2021/07/09 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/07/08 06:31 [entrez]
AID - 10.1038/s41409-021-01393-9 [pii]
AID - 10.1038/s41409-021-01393-9 [doi]
PST - ppublish
SO  - Bone Marrow Transplant. 2021 Nov;56(11):2714-2722. doi: 
      10.1038/s41409-021-01393-9. Epub 2021 Jul 7.