Department of Respiratory Medicine and Hematology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Department of Hematology-Oncology, Chiba Cancer Center, Chiba, Japan.
Int J Hematol. 2022 Aug;116(2):248-257. doi: 10.1007/s12185-022-03342-8. Epub 2022 May 6.
Anti-thymocyte globulin (ATG) is an important prophylactic drug against acute graft-versus-host disease (aGVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study analyzed the pharmacokinetics of rabbit ATG 2.5 mg/kg and its effect against aGVHD in 24 patients undergoing unmanipulated haplo-HSCT. All patients had hematological malignancies not in remission. The median absolute lymphocyte count (ALC) before rabbit ATG administration was 9.5/µL (range 0-41/µL). The grade ≥ II aGVHD group had a significantly lower median rabbit ATG concentration on days 0 (C) and 7 (C) and areas under the curve on days 0-7 (AUC) and 0-32 (AUC) than the grade 0-I aGVHD group. Among the four parameters, C was the most optimal for predicting aGVHD according to the receiver-operating characteristic (ROC) analysis (area under the ROC curve 0.893; 95% confidence interval 0.738-1.000). The high C (≥ 27.8 µg/mL) group had significantly lower cumulative incidence of grade ≥ II aGVHD on day 100 than the low C (< 27.8 µg/mL) group (13.8% vs. 88.9%, p < 0.001). In haplo-HSCT, the C of rabbit ATG is a good predictor of grade ≥ II aGVHD, even though ALC before rabbit ATG administration is not a predictor of aGVHD.
抗胸腺细胞球蛋白(ATG)是预防单倍体造血干细胞移植(haplo-HSCT)后急性移植物抗宿主病(aGVHD)的重要药物。本研究分析了 24 例未经预处理的单倍体 HSCT 患者中 2.5mg/kg 兔 ATG 的药代动力学及其对 aGVHD 的作用。所有患者均患有未缓解的血液系统恶性肿瘤。兔 ATG 给药前的中位绝对淋巴细胞计数(ALC)为 9.5/µL(范围 0-41/µL)。Ⅱ级及以上 aGVHD 组兔 ATG 浓度在 0 天(C)和 7 天(C)以及 0-7 天(AUC)和 0-32 天(AUC)的 AUC 明显低于 0-1 级 aGVHD 组。在这四个参数中,C 根据受试者工作特征(ROC)分析是预测 aGVHD 最理想的参数(ROC 曲线下面积 0.893;95%置信区间 0.738-1.000)。C 较高(≥27.8µg/mL)组第 100 天的Ⅱ级及以上 aGVHD 累积发生率明显低于 C 较低(<27.8µg/mL)组(13.8% vs. 88.9%,p<0.001)。在 haplo-HSCT 中,兔 ATG 的 C 是预测Ⅱ级及以上 aGVHD 的良好指标,尽管兔 ATG 给药前的 ALC 不是 aGVHD 的预测指标。