Yuan Jiaojiao, Pei Renzhi, Su Wensi, Cao Junjie, Lu Ying
Medical School of Ningbo University, Ningbo, Zhejiang, P.R. China.
Department of Hematology, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, Zhejiang, P.R. China.
Oncotarget. 2017 Feb 14;8(7):10871-10882. doi: 10.18632/oncotarget.14719.
Graft-versus-host disease (GVHD) is a serious complication associated with allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin (ATG) is widely used prior to allo-HCT for GVHD prevention, though evidence of its efficacy remains unclear. We therefore identified nine randomized controlled trials (RCTs), enrolling 1089 patients (554 in the ATG group and 535 in the non-ATG group) to conduct a meta-analysis of the actions of ATG in allo-HCT. A relative risk or risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome. Rabbit ATG reduced overall acute (a) GVHD (RR 0.77, 95% CI 0.67-0.89, P = 0.0004), grade III-IV aGVHD (RR 0.53, 95% CI 0.32-0.88, P = 0.01), overall chronic (c) GVHD (RR 0.52, 95% CI 0.42-0.64, P < 0.00001) and extensive cGVHD (RR 0.28, 95% CI 0.18-0.43, P < 0.00001), without increased risk of relapse (RR 1.17, 95% CI 0.91-1.49, P = 0.23). By contrast, horse ATG did not reduce overall aGVHD (RR 1.25, 95% CI 0.88-1.79, P = 0.22) or cGVHD (RR 1.67, 95% CI 0.96-2.91, P = 0.07). ATG marginally reduced 100-day transplant related mortality (RR 0.75, 95% CI 0.56-1.00, P = 0.05) without compromising overall survival or increased risk of infections. Further studies are required to evaluate the optimal dosage and formulation of ATG in different conditioning regimens of transplantation with varied sources of graft and donor.
移植物抗宿主病(GVHD)是异基因造血细胞移植(allo-HCT)相关的一种严重并发症。抗胸腺细胞球蛋白(ATG)在allo-HCT前被广泛用于预防GVHD,但其疗效证据仍不明确。因此,我们确定了9项随机对照试验(RCT),纳入1089例患者(ATG组554例,非ATG组535例),对ATG在allo-HCT中的作用进行荟萃分析。计算每个结局的相对危险度或风险比(RR)及95%置信区间(CI)。兔ATG降低了总体急性(a)GVHD(RR 0.77,95%CI 0.67-0.89,P = 0.0004)、III-IV级aGVHD(RR 0.53,95%CI 0.32-0.88,P = 0.01)、总体慢性(c)GVHD(RR 0.52,95%CI 0.42-0.64,P < 0.00001)和广泛性cGVHD(RR 0.28,95%CI 0.18-0.43,P < 0.00001),且复发风险未增加(RR 1.17,95%CI 0.91-1.49,P = 0.23)。相比之下,马ATG未降低总体aGVHD(RR 1.25,95%CI 0.88-1.79,P = 0.22)或cGVHD(RR 1.67,95%CI 0.96-2.91,P = 0.07)。ATG略微降低了100天移植相关死亡率(RR 0.75, 95%CI 0.56-1.00, P = 0.05),且不影响总体生存率或增加感染风险。需要进一步研究以评估在不同移植预处理方案、不同移植物和供体来源情况下ATG的最佳剂量和剂型。