L-Asparaginase for newly diagnosed extra-nodal NK/T-cell lymphoma: systematic review and meta-analysis

<b>Objectives:</b> The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients. <b>Methods:</b> The PRISMA protocol was used to search PubMed and Embase for both controlled and uncontrolled studies of ASP or alternative chemotherapy (CT) for newly diagnosed ENKTL, published in English by March 2017. The regimens were compared to calculate relative risk (RR) with 95% confidence interval (CI) of the overall response rate (ORR), complete response (CR) or partial response (PR). <b>Results:</b> Out of 38 studies included, eight were controlled trials, with the pooled RR of ORR in stage I-II 1.54 (95% CI 1.34–1.77); stage I-IV 1.34 (95% CI 1.09–1.64). In stage III-IV CT combined with radiotherapy (RT), RR of ORR was 2.30 (95% CI 1.66–3.18). ASP was also superior in achieving CR. When all single arms combined, RR of ORR after CT with ASP was 1.52 (95% CI 1.38–1.67) in stage I-II (15 studies); 1.44 (95% CI 1.32–1.57) in all stages (29 studies); 1.31 (95% CI 1.24–1.38) and 1.66 (95% CI 1.18–2.34) in stages I-II and III-IV combined with RT, correspondingly. <b>Conclusions:</b> ASP-based CT significantly improved ORR and CR in patients with newly diagnosed both early-stage and advanced-stage ENKTL.

**研究目的**：本系统综述旨在对比含门冬酰胺酶（asparaginase，ASP）方案与不含ASP方案在结外NK/T细胞淋巴瘤（ENKTL）患者一线治疗中的疗效。
**研究方法**：本研究遵循系统综述与Meta分析优先报告条目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses，PRISMA）指南，检索PubMed与Embase数据库，筛选2017年3月前发表的英文文献，纳入针对新确诊ENKTL患者、采用ASP或其他化疗（chemotherapy，CT）方案的对照与非对照研究。对比不同治疗方案，计算总体缓解率（overall response rate，ORR）、完全缓解（complete response，CR）或部分缓解（partial response，PR）的相对危险度（relative risk，RR）及95%置信区间（95% confidence interval，CI）。
**研究结果**：最终纳入38项研究，其中8项为对照试验。I-II期患者的合并ORR相对危险度为1.54（95%CI 1.34~1.77），I-IV期患者为1.34（95%CI 1.09~1.64）。在III-IV期患者中，化疗联合放疗（radiotherapy，RT）的ORR相对危险度为2.30（95%CI 1.66~3.18）。门冬酰胺酶在实现完全缓解方面同样更具优势。对所有单臂研究进行合并分析后，I-II期（15项研究）接受含ASP化疗患者的ORR相对危险度为1.52（95%CI 1.38~1.67）；全分期（29项研究）患者为1.44（95%CI 1.32~1.57）；I-II期联合放疗、III-IV期联合放疗患者的ORR相对危险度分别为1.31（95%CI 1.24~1.38）与1.66（95%CI 1.18~2.34）。
**结论**：以门冬酰胺酶为基础的化疗方案可显著提升新确诊的早期及晚期ENKTL患者的总体缓解率与完全缓解率。