title: Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplant depends on transplantation conditioning intensity.
abstract: We examined the clinical impact of killer-immunoglobulin receptor-ligand (KIR-L) mismatch in 257 recipients of single (n = 91) or double (n = 166) unit umbilical cord blood (UCB) grafts after myeloablative (n = 155) or reduced intensity (n = 102) conditioning regimens. Analyses of double unit grafts considered the KIR-L match status of the dominant engrafting unit. After myeloablative conditioning, KIR-L mismatch had no effect on grade III-IV acute graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse, and survival. In contrast, after reduced intensity conditioning, KIR-L mismatch between the engrafted unit and the recipient resulted in significantly higher rates of grade III-IV acute GVHD (42% [CI, 27-59] vs 13% [CI, 5-21], P < .01) and TRM (27% [CI, 12%-42%] vs 12% [CI, 5%-19%], P = .03) with inferior survival (32% [CI, 15%-59%] vs 52% [CI, 47%-67%], P = .03). Multivariate analysis identified KIR-L mismatch as the only predictive factor associated with the development of grade III-IV acute GVHD (RR, 1.8 [CI, 1.1-2.9]; P = .02) and demonstrated a significant association between KIR-L mismatch and increased risk of death (RR, 1.8; 95% CI, 1.0-3.1; P = .05). Our results do not support the selection of UCB units based on KIR-L status and suggest that KIR-L mismatching should be avoided in reduced intensity UCB transplantation.
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Claudio G
authors.initials: CG
authors.lastname: Brunstein
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.forename: Harriet
authors.initials: H
authors.lastname: Noreen
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Barker
authors.forename: Todd
authors.initials: T
authors.lastname: DeFor
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller