Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Hematology, Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
BMC Med. 2019 Aug 12;17(1):156. doi: 10.1186/s12916-019-1393-7.
The optimal dose of rabbit antithymocyte globulin (ATG, ImtixSangstat) minimizing infections without increasing graft-versus-host disease (GVHD) is unknown in T cell-replete, G-CSF-primed haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
Four hundred and eight patients were enrolled in this multicenter study to evaluate the effect of 7.5 mg/kg and 10.0 mg/kg rabbit ATG on viral infections and GVHD prophylaxis after haplo-HSCT. The primary endpoint was EBV DNAemia within 1 year posttransplantation.
The 1-year incidence of EBV DNAemia was 20.7% (95% confidence interval, 15.4-26.5) and 40.0% (33.3-46.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (P < 0.001). The 100-day cumulative incidence of grade II to IV aGVHD was 27.1% (21.1-33.4) and 25.4% (19.6-31.5) in the 7.5 mg/kg and 10.0 mg/kg ATG groups, respectively (P = 0.548). The 2-year incidence of chronic GVHD was 34.6% (27.8-41.4) and 36.2% (29.1-43.2) in the 7.5 mg and 10.0 mg groups (P = 0.814). The 1-year incidence of CMV DNAemia was 73.4% (67.2-79.4) and 83.4% (77.5-87.9) in the 7.5 mg/kg and 10.0 mg/kg groups (P = 0.038). The 3-year overall survival posttransplantation was 69.5% (63.2-75.8) and 63.5% (56.2-70.8), and the disease-free survival was 62.2% (55.3-69.1) and 60.3% (53.0-67.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (OS: P = 0.308; DFS: P = 0.660). The counts of EBV- and CMV-specific cytotoxic T cells (CTLs) were higher in the 7.5 mg/kg group than in the 10.0 mg/kg group early posttransplantation.
Compared with 10.0 mg/kg, 7.5 mg/kg ATG for GVHD prophylaxis was associated with reduced EBV and CMV infections without increased incidence of GVHD in haplo-HSCT, probably by affecting EBV- and CMV-specific CTLs.
clinicaltrials.gov, NCT01883180 . Registered 14 June 2013.
在 T 细胞充足、粒细胞集落刺激因子（G-CSF）预处理的半相合造血干细胞移植（haplo-HSCT）中，最小化感染而不增加移植物抗宿主病（GVHD）的兔抗胸腺细胞球蛋白（ATG，ImtixSangstat）最佳剂量尚不清楚。
本多中心研究纳入了 408 例患者，以评估 7.5mg/kg 和 10.0mg/kg 兔 ATG 对 haplo-HSCT 后病毒感染和 GVHD 预防的影响。主要终点是移植后 1 年内 EBV DNAemia。
7.5mg/kg 和 10.0mg/kg 组 EBV DNAemia 的 1 年发生率分别为 20.7%（95%置信区间，15.4-26.5）和 40.0%（33.3-46.6）（P<0.001）。7.5mg/kg 和 10.0mg/kg ATG 组的 100 天累积 II 至 IV 级 aGVHD 发生率分别为 27.1%（21.1-33.4）和 25.4%（19.6-31.5）（P=0.548）。慢性 GVHD 的 2 年发生率分别为 34.6%（27.8-41.4）和 36.2%（29.1-43.2）（P=0.814）。7.5mg/kg 和 10.0mg/kg 组的 CMV DNAemia 的 1 年发生率分别为 73.4%（67.2-79.4）和 83.4%（77.5-87.9）（P=0.038）。移植后 1 年的总生存率分别为 69.5%（63.2-75.8）和 63.5%（56.2-70.8），无病生存率分别为 62.2%（55.3-69.1）和 60.3%（53.0-67.6）（OS：P=0.308；DFS：P=0.660）。移植后早期，7.5mg/kg 组 EBV 和 CMV 特异性细胞毒性 T 细胞（CTL）的计数高于 10.0mg/kg 组。
与 10.0mg/kg 相比，7.5mg/kg ATG 用于 GVHD 预防可降低 EBV 和 CMV 感染的发生率，而不增加 haplo-HSCT 中的 GVHD 发生率，这可能是通过影响 EBV 和 CMV 特异性 CTLs 实现的。
clinicaltrials.gov，NCT01883180。2013 年 6 月 14 日注册。
