Optimal Dose of Rabbit Thymoglobulin in Conditioning Regimens for Unmanipulated, Haploidentical, Hematopoietic Stem Cell Transplantation: Long-Term Outcomes of a Prospective Randomized Trial
Optimal Dose of Rabbit Thymoglobulin in Conditioning Regimens for Unmanipulated, Haploidentical, Hematopoietic Stem Cell Transplantation: Long-Term Outcomes of a Prospective Randomized Trial
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非操作、单倍相合造血干细胞移植预处理方案中兔胸腺球蛋白的最佳剂量：一项前瞻性随机试验的长期结果。
DOI：
10.1002/cncr.30540
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发表时间：
2017-08-01
期刊：
影响因子：
6.2
通讯作者：
Huang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Chang, Ying-Jun;Wang, Yu;Huang, Xiao-Jun
背景：抗胸腺细胞球蛋白（ATG）是治疗方案的一个重要组成部分，用于预防未经处理的单倍体干细胞移植（haploi - sct）患者的严重移植物抗宿主病（GVHD）。然而，据作者所知，ATG的最佳剂量是未知的。方法：在这项前瞻性随机试验中，作者比较了在未经操作的单倍造血干细胞移植前用于清髓调节的2种剂量的ATG（兔胸腺球蛋白）的长期结果。患者被随机分配（1:1）接受10mg/kg （ATG-10）或6mg /kg （ATG-6）的ATG治疗。无病生存期、无GVHD /无复发生存期（GRFS）、疾病复发率、非复发死亡率和慢性GVHD （cGVHD）的分析包括整个人群。在存活至少6个月且接受定期随访评估的无病患者中评估晚期效应。结果：共纳入224例患者。中位随访期为1614天（范围281929天）。ATG-10组感染相关死亡率是ATG-6组的两倍（14.3% vs 7.1%； P= 0.084）。ATG-6组和ATG-10组的5年累积发病率在疾病复发率（12.8% vs 13.4%， P= 0.832）和非复发死亡率（11.6% vs 17.0%， P= 0.263）方面具有可比性。两组间的5年无病生存率具有可比性（75.6% vs 69.6%； P= 0.283）。ATG-6组cGVHD的5年累积发病率更高（75.0% vs 56.3% [P=.007]），中重度cGVHD: 56.3% vs 30.4% [P=.007]
BACKGROUND: 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. METHODS: 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 10mg/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. RESULTS: A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 281929 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