KIR Ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy
KIR Ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy
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DOI：
10.1016/j.bbmt.2006.04.008
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发表时间：
2006-08-01
影响因子：
4.3
通讯作者：
Petersdorf, Effie
中科院分区：
文献类型：
--
作者：
Hsu, Katharine C.;Gooley, Ted;Petersdorf, Effie
恶性肿瘤复发仍然是异基因造血细胞移植（HCT）后的一个重要并发症。减少复发的努力包括供体淋巴细胞输注以刺激供体抗受体T细胞同种异体识别主要和次要组织相容性差异。最近，已经描述了供体自然杀伤细胞介导的抑制性杀伤免疫球蛋白样受体（KIR）识别受体HLA-C和-B配体的同种异体反应性效应。我们研究了KIR配体对1770例患者复发风险的影响，这些患者接受了来自HLA匹配或不匹配的无关供体的清髓性T细胞造血干细胞移植（HCT），用于治疗髓系和淋巴系白血病。由HLA-B和-C基因型定义的KIR配体用于确定供体-受体配体不相容性或受体缺乏KIR配体。在HLA不匹配的移植中，受体HLA-B或-C KIR表位纯合性预示着缺乏KIR配体，并与复发风险降低相关（风险比，0.61; 95%置信区间，0.043 -0.85; P = 0.004）。缺乏HLA-C组2或HLA-Bw 4 KIR配体与较低的复发风险相关（风险比，0.47; 95%置信区间，0.28-0.79，P = 0.004;风险比，0.56; 95%置信区间，0.33-0.97; P = 0.04）。急性髓性白血病患者复发风险的降低与慢性髓性白血病和急性淋巴细胞白血病患者相似（P = 0.95）。定义KIR配体的HLA-B或-C表位的纯合性可能是HLA错配无关供者的清髓性HCT后白血病复发的预测因素。这种效应在HLA相同的无关移植中没有观察到。(C)2006年美国血液和骨髓移植学会。
Recurrent malignancy remains a significant complication after allogeneic hematopoietic cell transplantation (HCT). Efforts to decrease relapse have included donor lymphocyte infusion to stimulate donor anti-recipient T-cell allorecognition of major and minor histocompatibility differences. Recently, alloreactive effects of donor natural killer cell-mediated inhibitory killer immunoglobulin-like receptor (KIR) recognition of recipient HLA-C and -B ligands have been described. We examined KIR ligand effects on risk of relapse in 1770 patients undergoing myeloablative T-replete HCT from HLA-matched or -mismatched unrelated donors for the treatment of myeloid and lymphoid leukemias. KIR ligands defined by HLA-B and -C genotypes were used to determine donor-recipient ligand incompatibility or recipient lack of KIR ligand. Among HLA-mismatched transplantations, recipient homozygosity for HLA-B or -C KIR epitopes predicted lack of KIR ligand and was associated with a decreased hazard of relapse (hazard ratio, 0.61; 95% confidence interval,.043-0.85; P =.004). Absence of HLA-C group 2 or HLA-Bw4 KIR ligands was associated with lower hazards of relapse (hazard ratio, 0.47; 95% confidence interval, 0.28-0.79, P =.004; hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; P =.04, respectively). The decrease in hazard of relapse in patients with acute myelogenous leukemia was similar to that in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia (P =.95). Recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse after myeloablative HCT from HLA-mismatched unrelated donors. This effect was not observed in HLA-identical unrelated transplants. (C) 2006 American Society for Blood and Marrow Transplantation.