Jin Xuelian, Yang Yu, Chen Xinchuan
Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Ann Hematol. 2025 Mar;104(3):1317-1328. doi: 10.1007/s00277-025-06199-z. Epub 2025 Jan 23.
Post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are mainstay prophylactic treatment options for graft-versus-host disease (GVHD), widely used in haploidentical stem cell transplantation. Due to a lack of prospective studies, a number of retrospective comparisons have yielded different conclusions as to which prophylaxis regimen is superior. We performed a meta-analysis of these studies to get more informed and comprehensive decisions from clinicians. Nine studies were eligible, and a total of 1674 patients were included. The combined hazard ratio (HR), relative risk (RR), and weighted mean difference (WMD) results demonstrated that, compared with ATG, PTCy demonstrated better overall survival (OS) (HR 0.7, 95% CI 0.51-0.97), leukemia-free survival (LFS) (HR 0.66, 95% CI 0.53-0.81), and GVHD-free/relapse-free survival (GRFS) (HR 0.79, 95% CI 0.65-0.97); faster lymphocyte reconstitution, lower risk of relapse (HR 0.69, 95% CI 0.53-0.9) and fungal infection (RR 0.23, 95% CI 0.07-0.79). However, neutrophil engraftment was delayed in the PTCy regimen group (WMD 3.29, 95% CI 2.49-4.10). No statistically significant differences were observed in the time to platelet engraftment, bacterial infection, or viral infection, including cytomegalovirus, polyomaviruses BK/JC and Epstein-Barr virus. Nor was any statistically significant difference observed in the incidences of II-IV acute-GVHD (aGVHD) (HR 0.81, 95% CI 0.62-1.05), III-IV aGVHD (HR 0.67, 95% CI 0.22-2.19) or severe chronic-GVHD (cGVHD) (RR 1.22, 95% CI 0.51-2.88), or non-relapse mortality (NRM) outcomes (HR 0.67, 95% CI 0.4-1.11). Therefore, in haploidentical transplantation, PTCy accelerates lymphocyte reconstitution, significantly reduces the risk of recurrence and fungal infection, and improves the OS, LFS and GRFS, compared with ATG, with no significant difference in the efficacy of preventing acute or severe cGVHD, or the risk of bacterial or viral infection.
移植后环磷酰胺（PTCy）和抗胸腺细胞球蛋白（ATG）是移植物抗宿主病（GVHD）的主要预防性治疗选择，广泛用于单倍体相合干细胞移植。由于缺乏前瞻性研究，一些回顾性比较对于哪种预防方案更优得出了不同结论。我们对这些研究进行了荟萃分析，以便临床医生做出更明智、更全面的决策。9项研究符合条件，共纳入1674例患者。合并风险比（HR）、相对风险（RR）和加权平均差（WMD）结果表明，与ATG相比，PTCy在总生存期（OS）（HR 0.7，95%CI 0.51 - 0.97）、无白血病生存期（LFS）（HR 0.66，95%CI 0.53 - 0.81）和无GVHD/无复发生存期（GRFS）（HR 0.79，95%CI 0.65 - 0.97）方面表现更好；淋巴细胞重建更快，复发风险（HR 0.69，95%CI 0.53 - 0.9）和真菌感染风险（RR 0.23，95%CI 0.07 - 0.79）更低。然而，PTCy方案组中性粒细胞植入延迟（WMD 3.29，95%CI 2.49 - 4.10）。在血小板植入时间、细菌感染或病毒感染（包括巨细胞病毒、BK/JC多瘤病毒和爱泼斯坦 - 巴尔病毒）方面未观察到统计学显著差异。在II - IV级急性GVHD（aGVHD）（HR 0.81，95%CI 0.62 - 1.05）、III - IV级aGVHD（HR 0.67，95%CI 0.22 - 2.19）或重度慢性GVHD（cGVHD）（RR 1.22，95%CI 0.51 - 2.88）或非复发死亡率（NRM）结果（HR 0.67，95%CI 0.4 - 1.11）方面也未观察到统计学显著差异。因此，在单倍体相合移植中，与ATG相比，PTCy可加速淋巴细胞重建，显著降低复发和真菌感染风险，并改善OS、LFS和GRFS，在预防急性或重度cGVHD的疗效或细菌或病毒感染风险方面无显著差异。
