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

Authors
  • Brunstein, Claudio G
  • Wagner, John E
  • Weisdorf, Daniel J
  • Cooley, Sarah
  • Noreen, Harriet
  • Barker, Juliet N
  • DeFor, Todd
  • Verneris, Michael R
  • Blazar, Bruce R
  • Miller, Jeffrey S
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
May 28, 2009
Volume
113
Issue
22
Pages
5628–5634
Identifiers
DOI: 10.1182/blood-2008-12-197467
PMID: 19329778
Source
Medline
License
Unknown

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.

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