TY - JOUR
T1 - Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation
AU - Sekine, Takuya
AU - Marin, David
AU - Cao, Kai
AU - Li, Li
AU - Mehta, Pramod
AU - Shaim, Hila
AU - Sobieski, Catherine
AU - Jones, Roy
AU - Oran, Betul
AU - Hosing, Chitra
AU - Rondon, Gabriela
AU - Alsuliman, Abdullah
AU - Paust, Silke
AU - Andersson, Borje
AU - Popat, Uday
AU - Kebriaei, Partow
AU - Muftuoglu, Muharrem
AU - Basar, Rafet
AU - Kondo, Kayo
AU - Nieto, Yago
AU - Shah, Nina
AU - Olson, Amanda
AU - Alousi, Amin
AU - Liu, Enli
AU - Sarvaria, Anushruti
AU - Parmar, Simrit
AU - Armstrong-James, Darius
AU - Imahashi, Nobuhiko
AU - Molldrem, Jeffrey
AU - Champlin, Richard
AU - Shpall, Elizabeth J.
AU - Rezvani, Katayoun
N1 - Publisher Copyright:
© 2016 by The American Society of Hematology.
PY - 2016/7/14
Y1 - 2016/7/14
N2 - 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, KIRandHLA genotypes, and NK-cell reconstitution inCBTpatients (n5110).Resultswerevalidatedinanindependentcohort (n594).HLA-KIR genotypingof recipientgermlineandtransplantedcordblood(CB)graftspredictedfor 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 atCBT, recipient HLA-C2/C2 genotype, and donor HLA-KIR genotype were independent predictors of outcome. Thus, wepropose the inclusion of KIRgenotyping in graft selection criteria forCBT. 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.
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, KIRandHLA genotypes, and NK-cell reconstitution inCBTpatients (n5110).Resultswerevalidatedinanindependentcohort (n594).HLA-KIR genotypingof recipientgermlineandtransplantedcordblood(CB)graftspredictedfor 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 atCBT, recipient HLA-C2/C2 genotype, and donor HLA-KIR genotype were independent predictors of outcome. Thus, wepropose the inclusion of KIRgenotyping in graft selection criteria forCBT. 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.
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U2 - 10.1182/blood-2016-03-706317
DO - 10.1182/blood-2016-03-706317
M3 - Article
C2 - 27247137
AN - SCOPUS:84978375312
SN - 0006-4971
VL - 128
SP - 297
EP - 312
JO - Blood
JF - Blood
IS - 2
ER -