移植后 DSA 和 NDSA 影响血液系统恶性肿瘤患者无预先存在 HLA 抗体的单倍体 HSCT 后 GvHD、OS 和 DFS。
Posttransplant DSA and NDSA affect GvHD, OS, and DFS after haplo-HSCT in patients without pre-existing HLA antibodies of hematological malignancies.
机构信息
HLA Laboratory of Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Hematology, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
出版信息
Front Immunol. 2022 Dec 1;13:1047200. doi: 10.3389/fimmu.2022.1047200. eCollection 2022.
To examine the production time, type, and MFI of post-transplantation HLA antibodies, and their effects on haplo-HSCT outcomes, we retrospectively included 116 patients who were negative for pre-existing HLA antibodies. In total, 322 serum samples from pre-transplantation to post-transplantation were dynamically tested by Luminex and single-antigen bead reagents. Patients were divided into: HLA antibody persistently negative group (group 1), the HLA antibody transiently positive group (group 2), the HLA antibody non-persistently positive group (group 3), and the HLA antibody persistently positive group (group 4). Group 4 included DSA+non-DSA (NDSA) (group 4a) and NDSA (group 4b) groups. The detection rate of HLA antibodies was 75.9% (88/116). The median MFI for HLA antibodies was 2439 (1033-20162). The incidence of II-IV aGvHD was higher in group 2 than in group 1 (52.6% vs 17.9%, P < 0.01); in group 4a than in group 1 (87.5% vs 17.9%, P < 0.001); and in group 4a than in group 4b (87.5% vs 40.0%, P = 0.001). The DFS (37.5% vs 85.7%, P < 0.01) and OS (37.5% vs 85.7%, P < 0.01) of group 4a were lower than those of group 1. The DFS (48.0% vs 85.7%, P < 0.01) and OS (56.0% vs 85.7%, P = 0.03) of group 4b were lower than those of group 1. Multivariate analysis showed that HLA antibody being transiently positive (HR: 5.30; 95% CI: 1.71-16.42, P = 0.01) and persistently positive (HR: 5.67; 95% CI: 2.00-16.08, P < 0.01) were both associated with a higher incidence of II-IV aGvHD. Persistently positive HLA antibodies were a risk factor for reduced DFS (HR: 6.57; 95% CI: 2.08-20.70, P < 0.01) and OS (HR: 5.51; 95% CI: 1.73-17.53, P < 0.01). DSA and NDSA can be detected since 15 days after haplo-HSCT in patients without pre-existing HLA antibodies, and affect aGvHD, DFS, and OS. Haplo-HSCT patients must be monitored for HLA antibodies changes for appropriate preventive clinical management, and we recommend that 1-month post-transplantation is the best test time point.
为了研究移植后 HLA 抗体的产生时间、类型和 MFI 及其对单倍体 HSCT 结局的影响，我们回顾性纳入了 116 例预先不存在 HLA 抗体的患者。总共对 322 份来自移植前到移植后的血清样本进行了动态检测，采用 Luminex 和单抗原珠试剂。患者分为：HLA 抗体持续阴性组（第 1 组）、HLA 抗体一过性阳性组（第 2 组）、HLA 抗体非持续阳性组（第 3 组）和 HLA 抗体持续阳性组（第 4 组）。第 4 组包括 DSA+非 DSA（NDSA）（第 4a 组）和 NDSA（第 4b 组）。HLA 抗体的检出率为 75.9%（88/116）。HLA 抗体的中位 MFI 为 2439（1033-20162）。与第 1 组相比，第 2 组 II-IV 级移植物抗宿主病（aGvHD）的发生率更高（52.6% vs 17.9%，P<0.01）；第 4a 组比第 1 组更高（87.5% vs 17.9%，P<0.001）；第 4a 组比第 4b 组更高（87.5% vs 40.0%，P=0.001）。第 4a 组的无病生存率（DFS）（37.5% vs 85.7%，P<0.01）和总生存率（OS）（37.5% vs 85.7%，P<0.01）均低于第 1 组。第 4b 组的 DFS（48.0% vs 85.7%，P<0.01）和 OS（56.0% vs 85.7%，P=0.03）均低于第 1 组。多因素分析显示，HLA 抗体一过性阳性（HR：5.30；95%CI：1.71-16.42，P=0.01）和持续阳性（HR：5.67；95%CI：2.00-16.08，P<0.01）均与 II-IV 级 aGvHD 的发生率较高有关。持续阳性的 HLA 抗体是降低 DFS（HR：6.57；95%CI：2.08-20.70，P<0.01）和 OS（HR：5.51；95%CI：1.73-17.53，P<0.01）的危险因素。无预先存在 HLA 抗体的单倍体 HSCT 患者自移植后 15 天即可检测到 DSA 和 NDSA，并影响 aGvHD、DFS 和 OS。单倍体 HSCT 患者必须监测 HLA 抗体的变化以进行适当的预防性临床管理，我们建议移植后 1 个月是最佳的检测时间点。
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