Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplant depends on transplantation conditioning intensity

Claudio G. Brunstein, John E. Wagner, Daniel J. Weisdorf, Sarah Cooley, Harriet Noreen, Juliet N. Barker, Todd DeFor, Michael R. Verneris, Bruce R. Blazar, Jeffrey S. Miller

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5628-5634
Number of pages7
JournalBlood
Volume113
Issue number22
DOIs
StatePublished - 2009

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