无关供者异基因造血干细胞移植中移植后环磷酰胺联合抗胸腺细胞球蛋白治疗：一项系统评价与荟萃分析

Post-transplant cyclophosphamide anti-thymocyte globulin in allogeneic hematopoietic stem cell transplantation from unrelated donors: A systematic review and meta-analysis.

作者信息

Tang Lu, Liu Zhigang, Li Tao, Dong Tian, Wu Qiuhui, Niu Ting, Liu Ting, Ji Jie

机构信息

West China Hospital, Sichuan University, Chengdu, China.

Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Oncol. 2023 Feb 16;13:1071268. doi: 10.3389/fonc.2023.1071268. eCollection 2023.

BACKGROUND

Post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are both common graft-versus-host disease (GVHD) prophylaxis strategies in allo-HSCT from unrelated donors. However, no consensus has reached on which regimen is optimal. Although several studies concerning this topic exist, the outcomes of different studies still conflict with each other. Therefore, an overall comparison of the two regimens is urgently needed to help make informed clinical decisions.

METHODS

Studies comparing PTCy and ATG regimens in unrelated donor (UD) allo-HSCT were searched in four critical medical databases from inception to April 17, 2022. The primary outcome was grade II-IV aGVHD, grade III-IV aGVHD and chronic GVHD (cGVHD), and the secondary outcomes included overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), and several severe infectious complications. The quality of articles was assessed by the Newcastle-Ottawa scale (NOS), and data were extracted by two independent investigators and then analyzed by RevMan 5.4.

RESULTS

Six out of 1091 articles were eligible for this meta-analysis. Compared with the ATG regimen, prophylaxis based on PTCy achieved a lower incidence of grade II-IV aGVHD incidence (RR=0.68, 95% CI 0.50-0.93, 0.010, 67%), grade III-IV aGVHD (RR=0.32, 95% CI 0.14-0.76, =0.001, 75%), NRM (RR=0.67, 95% CI 0.53-0.84, =0.17, 36%), EBV-related PTLD (RR=0.23, 95% CI 0.09-0.58, =0.85, 0%) and better OS (RR=1.29, 95% CI 1.03-1.62, 0.0001, 80%). The cGVHD, RI, CMV reactivation and BKV-related HC showed no significant difference between the two groups (RR=0.66, 95% CI 0.35-1.26, <0.00001, 86%; RR=0.95, 95% CI 0.78-1.16, =0.37, 7%; RR=0.89, 95% CI 0.63-1.24, =0.07, 57%; RR=0.88, 95% CI 0.76-1.03, =0.44, 0%).

CONCLUSION

In the setting of unrelated donor allo-HSCT, prophylaxis based on PTCy can lower the incidence of grade II-IV aGVHD, grade III-IV aGVHD, NRM and EBV-related complication, achieve better OS compared to ATG-based regimen. And cGVHD, RI, CMV reactivation and BKV-related HC were comparable in the two groups.

背景

移植后环磷酰胺（PTCy）和抗胸腺细胞球蛋白（ATG）都是无关供体异基因造血干细胞移植（allo-HSCT）中常见的移植物抗宿主病（GVHD）预防策略。然而，对于哪种方案是最佳方案尚未达成共识。尽管存在几项关于该主题的研究，但不同研究的结果仍然相互矛盾。因此，迫切需要对这两种方案进行全面比较，以帮助做出明智的临床决策。

方法

检索了四个关键医学数据库中从创建到2022年4月17日比较PTCy和ATG方案在无关供体（UD）allo-HSCT中的研究。主要结局是II-IV级急性移植物抗宿主病（aGVHD）、III-IV级aGVHD和慢性移植物抗宿主病（cGVHD），次要结局包括总生存期（OS）、复发率（RI）、非复发死亡率（NRM）以及几种严重感染并发症。文章质量通过纽卡斯尔-渥太华量表（NOS）进行评估，数据由两名独立研究人员提取，然后通过RevMan 5.4进行分析。

结果

1091篇文章中有6篇符合该荟萃分析的条件。与ATG方案相比，基于PTCy的预防方案在II-IV级aGVHD发生率（RR = 0.68，95% CI 0.50 - 0.93，P = 0.010，I² = 67%）、III-IV级aGVHD（RR = 0.32，95% CI 0.14 - 0.76，P = 0.001，I² = 75%）、NRM（RR = 0.67，95% CI 0.53 - 0.84，P = 0.17，I² = 36%）、EB病毒相关的移植后淋巴增殖性疾病（PTLD）（RR = 0.23，95% CI 0.09 - 0.58，P = 0.85，I² = 0%）方面发生率更低，并且OS更好（RR = 1.29，95% CI 1.03 - 1.62，P = 0.0001，I² = 80%）。两组之间的cGVHD、RI、巨细胞病毒（CMV）重新激活和BK病毒相关的出血性膀胱炎（HC）无显著差异（RR = 0.66，95% CI 0.35 - 1.26，P < 0.00001，I² = 86%；RR = 0.95，95% CI 0.78 - 1.16，P = 0.37，I² = 7%；RR = 0.89，95% CI 0.63 - 1.24，P = 0.07，I² = 57%；RR = 0.88，95% CI 0.76 - 1.03，P = 0.44，I² = 0%）。