Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia
Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia
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DOI：
10.1182/blood-2008-07-171926
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发表时间：
2009-01-15
期刊：
影响因子：
20.3
通讯作者：
Weisdorf, Daniel J.
中科院分区：
文献类型：
--
作者：
Cooley, Sarah;Trachtenberg, Elizabeth;Weisdorf, Daniel J.
急性髓系白血病(AML)患者的生存受到治疗相关死亡率(TRM)和非血缘关系供者(URD)造血细胞移植(HCT)后复发的限制。自然杀伤细胞(NK)细胞同种异体反应性由供者杀伤细胞免疫球蛋白样受体(KIRS)和受者人类白细胞抗原(HLA)决定，与AML成功的HCT相关。假设供者KIR基因型(A/A：2个A-KIR单倍型；B/x：至少1个B单倍型)会影响预后，我们对209例HLA相合和239例不相合T细胞全系URD移植的AML供者和受者进行了基因分型。从KIR B/x供者移植后的三年总存活率显著较高(31%[95%可信区间：26-36]对20%[95%可信区间：13-27]；P=0.007)。多变量分析显示，与A/A供者相比，B/x供者无复发生存的相对风险提高了30%(RR：0.70[95%CI：0.55-0.88]；P=0.002)。B/x供者与慢性移植物抗宿主病(GVHD；RR：1.51[95%CI：1.01-2.18]；P=0.03)相关，但与急性GVHD、复发或TRM无关。这一分析表明，具有KIR B单倍型的无关供者为AML接受T全血细胞移植的患者提供了显著的生存益处。对潜在供者进行KIR基因分型，除进行HLA分型外，还应识别具有B KIR单倍型的供者。(血。2009；113：726-732)
Survival for patients with acute myeloid leukemia (AML) is limited by treatment-related mortality (TRM) and relapse after unrelated donor (URD) hematopoietic cell transplantation (HCT). Natural killer (NK) cell alloreactivity, determined by donor killer-cell immunoglobulin-like receptors (KIRs) and recipient HLA, correlates with successful HCT for AML. Hypothesizing that donor KIR genotype (A/A: 2 A KIR haplotypes; B/x: at least 1 B haplotype) would affect outcomes, we genotyped donors and recipients from 209 HLA-matched and 239 mismatched T-replete URD transplantations for AML. Three-year overall survival was significantly higher after transplantation from a KIR B/x donor (31% [95% CI:26-36] vs 20% [95% CI: 13-27]; P = .007). Multivariate analysis demonstrated a 30% improvement in the relative risk of relapse-free survival with B/x donors compared with A/A donors (RR:0.70 [95% CI: 0.55-0.88]; P = .002). B/x donors were associated with a higher incidence of chronic graft-versus-host disease (GVHD; RR: 1.51 [95% CI: 1.01-2.18]; P = .03), but not of acute GVHD, relapse, or TRM. This analysis demonstrates that unrelated donors with KIR B haplotypes confer significant survival benefit to patients undergoing T-replete HCT for AML. KIR genotyping of prospective donors, in addition to HLA typing, should be performed to identify HLA-matched donors with B KIR haplotypes. (Blood. 2009; 113: 726-732)