PMID- 29549412
OWN - NLM
STAT- MEDLINE
DCOM- 20180427
LR  - 20180427
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 97
IP  - 6
DP  - 2018 Jun
TI  - Donor-recipient killer immunoglobulin like receptor (KIR) genotype matching has a 
      protective effect on chronic graft versus host disease and relapse incidence 
      following HLA-identical sibling hematopoietic stem cell transplantation.
PG  - 1027-1039
LID - 10.1007/s00277-018-3274-0 [doi]
AB  - Impact of donor-recipient killer immunoglobulin-like receptor (KIR) gene-gene 
      matching on transplant outcomes is still inconclusive. Recent data suggest that 
      killer cell immunoglobulin-like receptor (KIR) regulated natural killer cell (NK 
      cell) activity may contribute to graft versus leukemia (GvL) effects and graft 
      versus host disease (GvHD) after allogeneic hematopoietic stem cell 
      transplantation (allo-HSCT). This case-control study aims to evaluate the effects 
      of both aKIR and iKIR donor-recipient genotype matching on the outcomes of T cell 
      replete HLA-identical sibling allo-HSCTs in a homogenous young patient population 
      with myeloid leukemias. Five transplant outcomes including relapse rate (RR), 
      disease-free survival (DFS), overall survival (OS), cumulative incidences of 
      acute GvHD (aGvHD), and chronic GvHD (cGvHD) are investigated. Out of 96 
      HLA-identical sibling donor-recipient pairs, 34 were matched for activating KIR 
      (aKIR), 38 for inhibitory KIR (iKIR), and 20 for both aKIR and iKIR. Fourty-four 
      pairs were mismatched for both iKIR and aKIR. In univariate analysis, 
      aKIR-matching resulted with a decrease in relapse rate (RR) (hazard ratio [HR]: 
      0.4; p = 0.04) and an increase in disease-free survival (DFS) (HR: 0.5; 
      p = 0.03). In addition, cGvHD ocurred less frequently in the aKIR-matched (odds 
      ratio [OR]: 0.4; p = 0.04) or iKIR-matched (OR: 0.3; p = 0.009) cohorts. Matching 
      for both aKIR and iKIR was also associated with a decrease in cGvHD incidence 
      (OR: 0.3; p = 0.02). iKIR-matching had no effects on RR, OS, or DFS. Analysis of 
      donor haplotype effects showed haplotype-BB to have a tendency towards reduced 
      relapse rate (HR: 0.4; p = 0.08) and better OS (HR: 0.4; p = 0.04); haplotype-Bx 
      to increase the incidence of cGvHD (OR: 4.1; p = 0.03). In multivariate analysis, 
      DFS advantage remained significant for aKIR-matching (HR: 0.5; p = 0.04); cGvHD 
      incidence was reduced in the presence of iKIR-match (OR: 0.3; p = 0.02) and 
      increased in the presence of haplotype-AB and -BB donors (OR: 7.9; p = 0.02; OR: 
      5.1; p = 0.03, respectively). In an attempt to investigate the pathogenesis 
      underlying KIR-matching, we searched for residual NK/T cells on day 0 peripheral 
      blood samples of six additional recipients and noted the presence of CD3(+) 
      (7.0-91.4 x 10(6)/L) and CD56(+)57(+) (0.8-12.7 x 10(6)/L) cells. In conclusion, 
      conditioning regimen surviving recipient NK/T cells potentially influenced by 
      KIR-matching may contribute to GvL/GvH reactions.
FAU - Sahin, Ugur
AU  - Sahin U
AD  - Department of Hematology, Cebeci Hospital, Ankara University Faculty of Medicine, 
      06220, Ankara, Turkey.
FAU - Dalva, Klara
AU  - Dalva K
AD  - Department of Hematology, Cebeci Hospital, Ankara University Faculty of Medicine, 
      06220, Ankara, Turkey.
FAU - Gungor, Funda
AU  - Gungor F
AD  - Department of Hematology, Cebeci Hospital, Ankara University Faculty of Medicine, 
      06220, Ankara, Turkey.
FAU - Ustun, Celalettin
AU  - Ustun C
AD  - Department of Medicine, Division of Hematology, Oncology and Transplantation, 
      University of Minnesota, Minneapolis, MN, USA.
FAU - Beksac, Meral
AU  - Beksac M
AD  - Department of Hematology, Cebeci Hospital, Ankara University Faculty of Medicine, 
      06220, Ankara, Turkey. Meral.Beksac@medicine.ankara.edu.tr.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20180316
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - *Donor Selection
MH  - Female
MH  - *Genotype
MH  - Graft vs Host Disease/epidemiology/genetics/immunology/*prevention & control
MH  - Hematopoietic Stem Cell Transplantation/*adverse effects
MH  - Humans
MH  - Incidence
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL 
      Positive/epidemiology/immunology/prevention & control/*therapy
MH  - Leukemia, Myeloid, Acute/immunology/*therapy
MH  - Male
MH  - Middle Aged
MH  - Proportional Hazards Models
MH  - Receptors, KIR/*genetics
MH  - Retrospective Studies
MH  - Secondary Prevention
MH  - Siblings
MH  - Survival Analysis
MH  - Turkey/epidemiology
OTO - NOTNLM
OT  - GvHD
OT  - KIR
OT  - Myeloid leukemia
OT  - Relapse
OT  - Stem cell transplantation
EDAT- 2018/03/20 06:00
MHDA- 2018/04/28 06:00
CRDT- 2018/03/18 06:00
PHST- 2017/03/27 00:00 [received]
PHST- 2018/02/02 00:00 [accepted]
PHST- 2018/03/20 06:00 [pubmed]
PHST- 2018/04/28 06:00 [medline]
PHST- 2018/03/18 06:00 [entrez]
AID - 10.1007/s00277-018-3274-0 [pii]
AID - 10.1007/s00277-018-3274-0 [doi]
PST - ppublish
SO  - Ann Hematol. 2018 Jun;97(6):1027-1039. doi: 10.1007/s00277-018-3274-0. Epub 2018 
      Mar 16.