Donor natural killer cell allorecognition of missing self in haploidentical hernatopoietic transplantation for acute myeloid leukemia: challenging its predictive value
Donor natural killer cell allorecognition of missing self in haploidentical hernatopoietic transplantation for acute myeloid leukemia: challenging its predictive value
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DOI：
10.1182/blood-2006-07-038687
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发表时间：
2007-07-01
期刊：
影响因子：
20.3
通讯作者：
Velardi, Andrea
中科院分区：
文献类型：
--
作者：
Ruggeri, Loredana;Mancusi, Antonella;Velardi, Andrea
我们分析了112例高危急性髓系白血病患者，其中61例完全缓解(CR)，51例复发，接受了来自自然杀伤(NK)异基因反应供者(n=51)和非NK异基因反应供者(n=61)的人类白细胞抗原(HL A)半相合移植。NK同种异体反应供者具有受体缺失的HLA1类、杀伤细胞免疫球蛋白样受体(KIR)配体(S)、受体自身识别缺失的KIR基因(S)以及针对受体靶标的同种异体反应性NK克隆。NK同种异体反应性供者的移植与CR移植患者的复发率(3%比47%)显著降低(P>；.003)，在复发和缓解期移植的患者的无事件存活率(34%对6%，P=.04)和缓解期(67%对18%，P=0.02)，以及复发或死亡的风险降低(相对风险与非NK同种异体反应者，0.48；95%CI，0.29-0.78；P&gT；.001)。在所有患者中，我们测试了“缺失配体”模型，该模型汇集了来自拥有KIR的供者(S)的KIR配体不匹配的移植和来自供者和受者都没有HLAL的供者(S)的KIR配基匹配的移植。只有来自NK同种异体反应供者的移植才与生存优势相关。
We analyzed 112 patients with high-risk acute myeloid leukemia (61 in complete remission (CR]; 51 in relapse), who received human leukocyte-antigen (HLA)-haploidentical transplants from natural killer (NK) alloreactive (n = 51) or non-NK alloreactive donors (n = 61). NK alloreactive donors possessed HLA class 1, killer-cell immunoglobulin-like receptor (KIR) ligand(s) which were missing in the recipients, KIR gene(s) for missing self recognition on recipient targets, and alloreactive NK clones against recipient targets. Transplantation from NK-alloreactive donors was associated with a significantly lower relapse rate in patients transplanted in CR (3% versus 47%) (P > .003), better event-free survival in patients transplanted in relapse (34% versus 6%, P = .04) and in remission (67% versus 18%, P = .02), and reduced risk of relapse or death (relative risk versus non-NK-alloreactive donor, 0.48; 95% Cl, 0.29-0.78; P > .001). In all patients we tested the "missing ligand" model which pools KIR ligand mismatched transplants and KIR ligand-matched transplants from donors possessing KIR(s) for which neither donor nor recipient have HLA ligand(s). Only transplantation from NK-alloreactive donors is associated with a survival advantage.