Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplant depends on transplantation conditioning intensity
Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplant depends on transplantation conditioning intensity
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DOI：
10.1182/blood-2008-12-197467
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发表时间：
2009-05-28
期刊：
影响因子：
20.3
通讯作者：
Miller, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Brunstein, Claudio G.;Wagner, John E.;Miller, Jeffrey S.
我们研究了257例接受清髓性（n = 155）或降低强度（n = 102）预处理方案后单（n = 91）或双（n = 166）单位脐带血（UCB）移植的受者中标记物-免疫球蛋白受体-配体（KIR-L）不匹配的临床影响。双单位移植物的分析考虑了显性移植单位的KIR-L匹配状态。清髓性预处理后，KIR-L错配对III-IV级急性移植物抗宿主病（GVHD）、移植相关死亡率（TRM）、复发和生存率无影响。相反，在降低强度预处理后，移植单位和受体之间的KIR-L错配导致III-IV级急性GVHD的发生率显著升高（42% [CI，27-59] vs 13% [CI，5-21]，P < .01）和TRM（27% [CI，12%-42%] vs 12% [CI，5%-19%]，P = .03），生存率较低（32% [CI，15%-59%] vs 52% [CI，47%-67%]，P = .03）。多变量分析确定KIR-L错配是与发生III-IV级急性GVHD相关的唯一预测因素（RR，1.8 [CI，1.1-2.9]; P = .02），并证明KIR-L错配与死亡风险增加之间存在显著相关性（RR，1.8; 95%CI，1.0-3.1; P = .05）。我们的研究结果不支持基于KIR-L状态选择UCB单位，并建议在降低强度的UCB移植中应避免KIR-L错配。（血。2009; 113：5628-5634）
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. (Blood. 2009; 113: 5628-5634)