KIR/HLA受配体模式对血液病患者单份非血缘脐血移植预后的影响  

Effect of KIR/HLA receptor-ligand mode on prognosis of single unrelated cord blood transplantation in patients with hematological malignancies

作　　者：方婷婷 朱小玉 汤宝林 刘会兰 皖湘 宋闿迪 姚雯 孙光宇 方欣臣 孙自敏 Fang Tingting;Zhu Xiaoyu;Tang Baolin;Liu Huilan;Wan Xiang;Song Kaidi;Yao Wen;Sun Guangyu;Fang Xinchen;Sun Zimin(Department of Hematology,Anhui Provincial Hospital of Anhui Medical University,Hefei 230001,China)

机构地区：[1]安徽医科大学附属省立医院血液科,合肥230001

出　　处：《中华血液学杂志》2020年第3期204-209,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金(81470350);中央高校基本科研业务费专项(WK9110000001).

摘　　要：目的探讨自然杀伤细胞免疫球蛋白样受体(KIR)与人类白细胞抗原(HLA)受配体模式对血液病患者单份非血缘脐血移植(sUCBT)预后的影响。方法回顾性分析2012年7月至2018年6月270例接受sUCBT的血液病患者。移植前脐血及患者均进行HLA12个位点高分辨配型,选择移植物(脐血)的KIR均同时表达2DL1和2DL2/2DL3抑制性基因,根据患者KIR配体情况分为缺失组(C1/C1或C2/C2)和无缺失组(C1/C2)。结果270例血液病患者中男146例(54.1%),女124例(45.9%),中位年龄13(1~62)岁;缺失组174例(64.4%),无缺失组96例(35.6%)。全部患者均采用不含抗胸腺细胞球蛋白(ATG)清髓性预处理方案。缺失组、无缺失组粒细胞植入率均为98.9%(172/174、95/96),中位植入时间分别为16(10~41)d、17(11~33)d(P=0.705);血小板植入率分别为88.5%(154/174)、87.5%(84/96),中位植入时间分别为35(11~113)d、38.5(13~96)d(P=0.317);缺失组、无缺失组Ⅱ~Ⅳ级急性GVHD发生率分别为38.7%(95%CI 31.4%~45.9%)、50.0%(95%CI 39.6%~59.6%)(P=0.075),多因素分析显示KIR配体缺失是影响Ⅱ~Ⅳ度急性GVHD发生的独立保护性因素(P=0.036)。移植后3年累积复发率分别为17.7%(95%CI 11.7%~24.9%)、22.7%(95%CI 14.4%~32.2%)(P=0.288)。中位随访时间742(335~2512)d,缺失组、无缺失组3年总生存率分别为72.1%(95%CI 64.1%~78.6%)、60.5%(95%CI 47.9%~69.2%)(χ^2=3.629,P=0.079),3年无病生存率分别为64.9%(95%CI 56.2%~72.3%)、55.4%(95%CI 44.4%~65.0%)(χ^2=3.027,P=0.082),移植后180 d非复发死亡率分别为12.1%(95%CI 7.7%~17.4%)、16.7%(95%CI 10.0%~24.8%)(P=0.328)。结论在不含ATG清髓性预处理sUCBT血液病治疗体系中,缺失抑制性KIR配体患者移植后急性GVHD发生率更低。Objective To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen(KIR/HLA)receptor-ligand model in single unrelated cord blood transplantation(sUCBT).Methods Between July 2012 and June 2018,270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups.Group 1(n=174)patients lacked a C-ligand for inhibitory KIR on UCB NK cells(patients homozygous C1/C1 or C2/C2).Group 2(n=96)patients expressed both C ligands for inhibitory KIR in the receptor(patients heterozygous C1/C2).Results A total of 270 patients(146 males,124 females)with a median age of 13 years(1-62)were included in this retrospective study.All patients received a myeloablative conditioning regimen(without ATG).The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%,the median time of neutrophil engraftment for group 1 and 2 was 16(10-41)days vs 17(11-33)days(P=0.705).The ratio of platelet engraftment was 88.5%for group 1 and 87.5%for group 2,the median time of platelet engraftment was 35(11-113)days vs 38.5(13-96)days(P=0.317).The cumulative incidence ofⅡ-Ⅳacute GVHD in 100 days was 38.7%(95%CI 31.4%-45.9%)for group 1 and 50.0%(95%CI 39.6%-59.6%)for group 2(P=0.075),but multivariate analysis showed that HLA-C ligand absence was an independent protective factor forⅡ-Ⅳacute GVHD after transplantation(P=0.036).Patients in absence of a C-ligand for inhibitory KIRs(Group 1)showed a lower relapse rate than patients with both C-ligands(group 2):17.7%(95%CI 11.7%-24.9%)vs 22.7%(95%CI 4.4%-32.2%)after 3 years(P=0.288).The median follow-up time was 742(335-2512)days.The 3-year OS was 72.1%for group 1 and 60.5%for group 2(P=0.079).There was no statistically significant difference between the two groups in 3-year disease-free survival[64.9%(95%CI 56.2%-72.3%)vs 55.4%(95%CI 44.4%-65.0%)(χ^2=3.027,P=0.082)].Non-relapse mortality for group 1 was 12.1%(95%CI 7.7%-17.4%)and for group 2 was 16.7%(95%CI 10.0%-24.8%)(P=0.328).Conclusion Patients lacking a KIR-liga

关 键 词：自然杀伤细胞免疫球蛋白样受体 人类白细胞抗原 非血缘脐血移植 iKIR配体缺失 

分 类 号：R4[医药卫生—临床医学] R5