National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital & Peking University Institute of Hematology, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Beijing, China.
HLA. 2024 Jan;103(1):e15300. doi: 10.1111/tan.15300. Epub 2023 Nov 20.
This study investigates the influence of donor-specific anti-HLA antibodies (DSA) levels on primary poor graft function (PGF) and graft rejection (GR) after haploidentical stem cell transplantation (haplo-SCT) with rituximab desensitization. A total of 155 DSA-positive haplo-SCT candidates with mean fluorescence intensity (MFI) between 2000 and 10,000 were enrolled in this prospective clinical trial. Receiver operating characteristic (ROC) curves determined the optimal DSA MFI cutoff for identifying high-risk patients. Patients were categorized into two groups: DSA low-level group (2000 ≤ DSA MFI < 5000, Group A) and high-level group (5000 ≤ DSA MFI ≤ 10,000, Group B). The incidence of primary PGF was 6.5% (2.6%-10.3%), while GR incidence was 0.6% (0.0%-1.9%). Group A had significantly lower primary PGF rates than Group B (2.3% [0.0%-5.7%] vs. 12.9% [4.8%-21.0%], p = 0.017). Only one patient in Group B experienced GR. High DSA levels (5000 ≤ MFI ≤ 10,000) were identified as the sole independent risk factor for primary PGF and GR after haplo-SCT with rituximab desensitization (HR = 7.282, 95% CI 1.517-34.953, p = 0.013). The 4-year cumulative incidence of relapse, non-relapse mortality, disease-free survival, and overall survival were 14.7% (11.6%-17.8%), 16.3% (13.1%-19.4%), 69.0% (65.9%-76.2%), and 70.6% (66.4%-74.8%), respectively. DSA levels have an impact on efficiency of rituximab desensitization, and a DSA MFI threshold is provided for predicting primary PGF and GR.
本研究探讨了在使用利妥昔单抗脱敏的情况下，供体特异性抗 HLA 抗体（DSA）水平对单倍体造血干细胞移植（haplo-SCT）后原发性移植物功能不良（PGF）和移植物排斥（GR）的影响。共纳入 155 例 DSA 阳性的 haplo-SCT 候选者，其平均荧光强度（MFI）在 2000 至 10000 之间。受试者工作特征（ROC）曲线确定了用于识别高风险患者的最佳 DSA MFI 截止值。患者分为两组：低水平 DSA 组（2000≤DSA MFI＜5000，A 组）和高水平 DSA 组（5000≤DSA MFI≤10000，B 组）。原发性 PGF 的发生率为 6.5%（2.6%-10.3%），而 GR 的发生率为 0.6%（0.0%-1.9%）。A 组原发性 PGF 发生率明显低于 B 组（2.3%[0.0%-5.7%] vs. 12.9%[4.8%-21.0%]，p=0.017）。B 组仅有 1 例患者发生 GR。高 DSA 水平（5000≤MFI≤10000）是 haplo-SCT 后发生原发性 PGF 和 GR 的唯一独立危险因素（HR=7.282，95%CI 1.517-34.953，p=0.013）。4 年累积复发率、非复发死亡率、无病生存率和总生存率分别为 14.7%（11.6%-17.8%）、16.3%（13.1%-19.4%）、69.0%（65.9%-76.2%）和 70.6%（66.4%-74.8%）。DSA 水平对利妥昔单抗脱敏的疗效有影响，并提供了 DSA MFI 阈值用于预测原发性 PGF 和 GR。
