开发了一种将抗胸腺细胞球蛋白与移植后环磷酰胺(ATG/PTCy)结合用于预防移植物抗宿主病(GVHD)的新策略。本研究旨在对接受单倍体相合造血干细胞移植的血液系统恶性肿瘤患者中ATG/PTCy与ATG或PTCy的比较研究进行系统评价和荟萃分析。使用ReviewManager版本5.4进行Meta分析,分别计算二分数据和事件发生时间数据的合并风险比(RR)和风险比(HRs)。如果没有显著的异质性,则使用固定效应模型。文献检索和研究选择确定了14项符合条件的研究,包括随机对照试验和回顾性比较研究.采用不同的剂量调整策略,ATG的总剂量为2.5-10mg/kg,PTCy的总剂量为29-100mg/kg。荟萃分析结果表明,与ATG(RR0.52;95%CI:0.41-0.65;P<0.00001)和PTCy(RR0.53;95%CI:0.34-0.83;P=0.005)相比,ATG/PTCy与II-IV级急性GVHD的风险显着降低相关,而不会增加疾病复发的风险。此外,与ATG和PTCy相比,ATG/PTCy与显著更好的总生存率和无GVHD/无复发生存率相关。未来的研究需要进一步确定ATG/PTCy的益处并确定最佳剂量调整策略。
背景:单倍体干细胞移植(haplo-HSCT)与移植物抗宿主病(GVHD)的高发病率相关。已开发出一种将抗胸腺细胞球蛋白与移植后环磷酰胺(ATG/PTCy)结合用于预防GVHD的新策略,但其好处和风险仍不清楚。
目的:本研究旨在对接受haplo-HSCT的血液系统恶性肿瘤患者中ATG/PTCy与ATG或PTCy的比较研究进行系统评价和荟萃分析。
方法:在包括OvidMedline,Embase,Cochrane图书馆和中国生物医学(CBM)。两名研究者独立筛选合格的研究并提取数据。使用ReviewManager5.4版进行荟萃分析,使用通用逆方差方法获得事件发生时间结局的汇总风险比(HR),使用Mantel-Haenszel方法获得二分数据的合并风险比(RR)。如果没有显著的异质性,则采用固定效应模型。主要结果是急性GVHD的发生率。
结果:文献检索和研究选择确定了14项符合条件的研究,包括1项随机对照试验和13项回顾性比较研究.采用不同的剂量调整策略,ATG的总剂量为2.5-10mg/kg,PTCy的总剂量为29-100mg/kg。荟萃分析结果表明,与ATG(RR0.52;95%CI:0.41-0.65;P<0.00001)和PTCy(RR0.53;95%CI:0.34-0.83;P=0.005)相比,ATG/PTCy与II-IV级急性GVHD的风险显着降低相关,而不会增加疾病复发的风险。此外,与ATG相比,ATG/PTCy与III-IV级急性GVHD(RR0.33;95%CI:0.23-0.49;P<0.00001)和慢性GVHD(RR0.65;95%CI:0.51-0.81;P=0.0002)的风险显着降低。进一步的分析表明,与ATG和PTCy相比,ATG/PTCy与显著更好的总生存率和无GVHD/无复发生存率相关。但与PTCy相比,CMV(RR1.42;95%CI:1.03-1.95;P=0.03)和EBV(RR3.17;95%CI:1.61-6.23;P=0.0008)再激活的风险更高。
结论:我们的研究结果表明,ATG与PTCy联合用于HSCT中GVHD的预防与提高疗效相关,但感染风险更高。未来的研究需要进一步确定ATG/PTCy的益处和风险,并确定最佳剂量调整策略。
A new strategy combining anti-thymocyte globulin with post-transplant cyclophosphamide (ATG/PTCy) for graft-versus-host disease (GVHD) prevention was developed. This study aims to perform a systematic review and meta-analysis of studies comparing ATG/PTCy with ATG or PTCy in patients with hematological malignancies undergoing haploidentical hematopoietic stem cell transplantation. Meta-analysis was conducted with Review Manager version 5.4; pooled risk ratios (RRs) and hazard ratios (HRs) were calculated for dichotomous data and time-to-event data, respectively. A fixed-effects model was used if there was no significant heterogeneity. Literature search and study selection identified 14 eligible studies, including both randomized controlled trial and retrospective comparative studies. Different dosage adjustment strategies were applied; the total dose was 2.5-10 mg/kg for ATG and 29-100 mg/kg for PTCy. Meta-analysis results suggest that ATG/PTCy is associated with significantly lower risk of grades II-IV acute GVHD compared with ATG (RR 0.52; 95% CI: 0.41-0.65; P < .00001) and PTCy (RR 0.53; 95% CI: 0.34-0.83; P = .005) without increasing risk of disease relapse. In addition, ATG/PTCy is associated with significantly better overall survival and GVHD-free/relapse-free survival than ATG and PTCy. Future research is required to further establish the benefits of ATG/PTCy and determine the optimal dosage adjustment strategies.
BACKGROUND: Haploidentical stem cell transplantation (haplo-HSCT) is associated with higher incidences of graft-versus-host disease (GVHD). A new strategy combining anti-thymocyte globulin with post-transplant cyclophosphamide (ATG/PTCy) for GVHD prevention has been developed, but its benefits and risks remain unclear.
OBJECTIVE: This study aims to performs a systematic review and meta-analysis of studies comparing ATG/PTCy with ATG or PTCy in patients with hematological malignancies undergoing haplo-HSCT.
METHODS: Literature search was performed in databases including Ovid Medline, Embase, Cochrane Library and China Biology Medicine (CBM). Two investigators independently screened eligible studies and extracted data. Meta-analysis was conducted with Review Manager version 5.4; pooled hazard ratios (HRs) for time-to-event outcomes were obtained using a generic inverse-variance method, and pooled risk ratios (RRs) for dichotomous data were obtained using the Mantel-Haenszel method. A fixed-effects model was adopted if there was no significant heterogeneity. The primary outcome is incidence of acute GVHD.
RESULTS: Literature search and study selection identified 14 eligible studies, including both 1 randomized controlled trial and 13 retrospective comparative studies. Different dosage adjustment strategies were applied; the total dose was 2.5-10 mg/kg for ATG and 29-100 mg/kg for PTCy. Meta-analysis results suggest that ATG/PTCy is associated with significantly lower risk of grades II-IV acute GVHD compared with ATG (RR 0.52; 95% CI: 0.41-0.65; P < .00001) and PTCy (RR 0.53; 95% CI: 0.34-0.83; P = .005) without increasing risk of disease relapse. In addition, ATG/PTCy is associated with significantly lower risk of grades III-IV acute GVHD (RR 0.33; 95% CI: 0.23-0.49; P < .00001) and chronic GVHD (RR 0.65; 95% CI: 0.51-0.81; P = .0002) in comparison with ATG. Further analyses suggest that ATG/PTCy is associated with significantly better overall survival and GVHD-free/relapse-free survival than ATG and PTCy, but the risks of cytomegalovirus (RR 1.42; 95% CI: 1.03-1.95; P = .03) and Epstein Barr Virus (RR 3.17; 95% CI: 1.61-6.23; P = .0008) reactivation are higher when compared with PTCy.
CONCLUSIONS: Our results suggest that the combination of ATG with PTCy for GVHD prevention in haplo-HSCT is associated with improved efficacy but higher risk of infection. Future research is required to further establish the benefits and risks of ATG/PTCy and determine the optimal dosage adjustment strategies.