Imperial College London
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ProfessorDariusArmstrong-James

Faculty of Medicine, Department of Infectious Disease

Professor of Infectious Diseases and Medical Mycology
 
 
 
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d.armstrong

 
 
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Location

 

Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sekine:2016:10.1182/blood-2016-03-706317,
author = {Sekine, T and Marin, D and Cao, K and Li, L and Mehta, P and Shaim, H and Sobieski, C and Jones, R and Oran, B and Hosing, C and Rondon, G and Alsuliman, A and Paust, S and Andersson, B and Popat, U and Kebriaei, P and Muftuoglu, M and Basar, R and Kondo, K and Nieto, Y and Shah, N and Olson, A and Alousi, A and Liu, E and Sarvaria, A and Parmar, S and Armstrong-James, DPH and Imahashi, N and Molldrem, J and Champlin, R and Shpall, EJ and Rezvani, K},
doi = {10.1182/blood-2016-03-706317},
journal = {Blood},
pages = {297--312},
title = {Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation},
url = {http://dx.doi.org/10.1182/blood-2016-03-706317},
volume = {128},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The ability of cord blood transplantation (CBT) to prevent relapse depends partly on donor natural killer (NK) cell alloreactivity. NK effector function depends on specific killer-cell immunoglobulin-like receptors (KIR) and HLA interactions. Thus, it is important to identify optimal combinations of KIR-HLA genotypes in donors and recipients that could improve CBT outcome. We studied clinical data, KIR and HLA genotypes, and NK-cell reconstitution in CBT patients (n = 110). Results were validated in an independent cohort (n = 94). HLA-KIR genotyping of recipient germline and transplanted cord blood (CB) grafts predicted for large differences in outcome. Patients homozygous for HLA-C2 group alleles had higher 1-year relapse rate and worse survival after CBT than did HLA-C1/C1 or HLA-C1/C2 (HLA-C1/x) patients: 67.8% vs 26.0% and 15.0% vs 52.9%, respectively. This inferior outcome was associated with delayed posttransplant recovery of NK cells expressing the HLA-C2-specific KIR2DL1/S1 receptors. HLA-C1/x patients receiving a CB graft with the combined HLA-C1-KIR2DL2/L3/S2 genotype had lower 1-year relapse rate (6.7% vs 40.1%) and superior survival (74.2% vs 41.3%) compared with recipients of grafts lacking KIR2DS2 or HLA-C1. HLA-C2/C2 patients had lower relapse rate (44.7% vs 93.4%) and better survival (30.1% vs 0%) if they received a graft with the combined HLA-C2-KIR2DL1/S1 genotype. Relapsed/refractory disease at CBT, recipient HLA-C2/C2 genotype, and donor HLA-KIR genotype were independent predictors of outcome. Thus, we propose the inclusion of KIR genotyping in graft selection criteria for CBT. HLA-C1/x patients should receive an HLA-C1-KIR2DL2/L3/S2 CB graft, while HLA-C2/C2 patients may benefit from an HLA-C2-KIR2DL1/S1 graft.
AU  - Sekine,T
AU  - Marin,D
AU  - Cao,K
AU  - Li,L
AU  - Mehta,P
AU  - Shaim,H
AU  - Sobieski,C
AU  - Jones,R
AU  - Oran,B
AU  - Hosing,C
AU  - Rondon,G
AU  - Alsuliman,A
AU  - Paust,S
AU  - Andersson,B
AU  - Popat,U
AU  - Kebriaei,P
AU  - Muftuoglu,M
AU  - Basar,R
AU  - Kondo,K
AU  - Nieto,Y
AU  - Shah,N
AU  - Olson,A
AU  - Alousi,A
AU  - Liu,E
AU  - Sarvaria,A
AU  - Parmar,S
AU  - Armstrong-James,DPH
AU  - Imahashi,N
AU  - Molldrem,J
AU  - Champlin,R
AU  - Shpall,EJ
AU  - Rezvani,K
DO  - 10.1182/blood-2016-03-706317
EP  - 312
PY  - 2016///
SN  - 0006-4971
SP  - 297
TI  - Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood-2016-03-706317
UR  - http://hdl.handle.net/10044/1/41021
VL  - 128
ER  -
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