Chang Ying-Jun, Wang Yu, Mo Xiao-Dong, Zhang Xiao-Hui, Xu Lan-Ping, Yan Chen-Hua, Chen Huan, Chen Yu-Hong, Chen Yao, Han Wei, Wang Feng-Rong, Wang Jing-Zhi, Liu Kai-Yan, Huang Xiao-Jun
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
Cancer. 2017 Aug 1;123(15):2881-2892. doi: 10.1002/cncr.30540. Epub 2017 Mar 16.
Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown.
In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to received 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) of ATG. Analysis of disease-free survival, GVHD-free/recurrence-free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations.
A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 28-1929 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-6 arm (14.3% vs 7.1%; P = .084). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for disease recurrence (12.8% vs 13.4%; P = .832) and nonrecurrence mortality (11.6% vs 17.0%; P = .263). The 5-year probability of disease-free survival was comparable between the groups (75.6% vs 69.6%; P = .283). The 5-year cumulative incidence of cGVHD was found to be higher with ATG-6 (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]) as well as that for late effects (71.2% vs 56.9%; P = .043). The 5-year probability of GRFS was higher in the ATG-10 group (41.0% vs 26.8%; P = .008). In the multivariate analysis, ATG-10 was found to be associated with a lower risk of cGVHD and improved GRFS.
ATG-10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. Cancer 2017;123:2881-92. © 2017 American Cancer Society.
抗胸腺细胞球蛋白（ATG）是未处理的单倍体同基因干细胞移植（haplo-SCT）患者预防严重移植物抗宿主病（GVHD）预处理方案的重要组成部分。然而，据作者所知，ATG的最佳剂量尚不清楚。
在这项前瞻性随机试验中，作者比较了未处理的单倍体造血干细胞移植（haplo-HSCT）前采用清髓性预处理时使用的两种ATG剂量（兔抗胸腺细胞球蛋白）的长期疗效。患者被随机分配（1:1）接受10mg/kg（ATG-10）或6mg/kg（ATG-6）的ATG。无病生存、无GVHD/无复发生存（GRFS）、疾病复发、非复发死亡率和慢性GVHD（cGVHD）分析纳入了全部人群。对存活至少6个月且接受定期随访评估的无病患者评估晚期效应。
共招募了224例患者。中位随访期为1614天（范围28 - 1929天）。ATG-10组感染相关死亡发生率是ATG-6组的两倍（14.3%对7.1%；P = 0.084）。ATG-6组和ATG-10组疾病复发的5年累积发生率相当（12.8%对13.4%；P = 0.832），非复发死亡率也相当（11.6%对17.0%；P = 0.263）。两组无病生存的5年概率相当（75.6%对69.6%；P = 0.283）。发现ATG-6组cGVHD的5年累积发生率更高（75.0%对56.3%[P = 0.007]，中重度cGVHD：56.3%对30.4%[P<0.0001]），晚期效应也是如此（71.2%对56.9%；P = 0.043）。ATG-10组GRFS的5年概率更高（41.0%对26.8%；P = 0.008）。多因素分析发现，ATG-10与较低的cGVHD风险及改善的GRFS相关。
发现ATG-10与更好的GVHD预防及更优的GRFS相关，但感染相关死亡增加。《癌症》2017年；123:2881 - 92。©2017美国癌症协会
