Impact of Graft-versus-Graft Natural Killer Cell Alloreactivity on Single Unit Dominance After Double Umbilical Cord Blood Transplantation.

Background: Natural Killer (NK) cell alloreactivity is favored after double umbilical cord blood transplantation (dUCBT) in which cord blood (UCB) units and patients are often Human Leucocyte Antigen (HLA) class I mismatched. Generally, only 1 UCB unit persists after dUCBT. We hypothesize, that NK cell alloreactivity mediated by Killer cell Immunoglobulin-like Receptor (KIR) - HLA interactions may explain the dominance of 1UCB unit over the other after dUCBT. Methods: We investigated the impact of KIR+ NK cell alloreactivities on the dominance of 1 full UCB unit in 50 dUCBT. We analyzed the effects of the KIR/HLA genetic incompatibilities and studied cord blood cells at both the phenotypic and functional levels. Results: The genetic combination of KIR3DL1+ loser UCB unit/Bw4- winner UCB unit determined both the dominance of 1 UCB unit (Hazard Ratio=2.88[1.32-6.27], p=.0077) and correlated with an increased incidence of relapse (Hazard Ratio=4.91[1.39-17.3], p=.0134). It is interesting to note that cord blood cells exhibited extremely low HLA class I expression. Moreover, resting cord blood KIR3DL1+ NK cells exhibited a basal alloreactivity against Bw4- target cells that increased upon activation, thus triggering death by apoptosis. Conclusions: Our unicentric study suggests, for the first time, the significant impact of KIR+ NK cell alloreactivity in the determination of which UCB unit will dominate in dUCBT. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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