基于大剂量甲氨蝶呤的化疗用于新诊断的原发性中枢神经系统淋巴瘤诱导缓解：一项系统评价和荟萃分析。
High-dose methotrexate-based chemotherapy for induction remission of newly diagnosed primary CNS lymphoma: A systematic review and meta-analysis.
作者信息
Shi Han, Sun Xuefei, Wu Yuchen, Cui Qu, Sun Shengjun, Ji Nan, Liu Yuanbo
机构信息
Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
出版信息
Medicine (Baltimore). 2025 Jan 31;104(5):e41363. doi: 10.1097/MD.0000000000041363.
BACKGROUND
This study aimed to comprehensively assess the optimal regimen for high-dose methotrexate (HD-MTX) in treating primary central nervous system lymphoma (PCNSL).
METHODS
We have searched 8 databases, including PubMed, EMBASE, Cochrane Library, WOS, Epistemonikos, CNKI, WAN-FANG Database, and CBM, and were selected for the clinical trials about PCNSL. A total of 37 studies were included in our analysis, consisting of 6 randomized controlled trials and 31 single-arm clinical studies.
RESULTS
After analyzing the data from 37 clinical studies, we found that the pooled overall response rate (ORR) for low-dose (<3 g/m2), medium-dose (3-5 g/m2), and high-dose (>5 g/m2) methotrexate (MTX) were 0.78, 0.80, and 0.80, respectively. The pooled 2-year overall survival (OS) for low-dose, medium-dose, and high-dose MTX were 52%, 60%, and 71%, respectively. The ORR, complete response (CR), and 2-year OS of patients who received <5 cycles of MTX were 79%, 41%, and 59%, respectively, whereas those for PCNSL patients who received >5 cycles of MTX were 81%, 54%, and 64%, respectively. The pooled ORR for MTX, dual therapy, triplet therapy, tetrad therapy, and multiple therapy were 71%, 70%, 81%, 85%, and 80%, respectively. The pooled 2-year OS for different numbers of medication combinations were 59%, 52%, 66%, 63%, and 60%, respectively. The addition of cytarabine to MTX-based chemotherapy resulted in higher CR, although no statistically significant difference was observed in OS. Adding rituximab to the treatment regimen improved patients' progression-free survival without affecting treatment response or OS.
CONCLUSION
Based on the findings of this study, the treatment strategies of MTX are associated with the prognosis and efficacy response of PCNSL patients. The results suggested that the current recommended HD-MTX dosage of 3.5 g/m2 is sufficient for PCNSL to have a favorable treatment response and prognosis. When the number of MTX treatment cycles increases, the therapeutic effect and prognosis of PCNSL patients are improved. The patients treated with MTX-based triplet combination regimens have a better ORR and CR. Although HD-MTX is generally well tolerated, it is necessary to be cautious about the use of multiple therapy that includes cytarabine to prevent potential acute toxicity.
背景
本研究旨在全面评估大剂量甲氨蝶呤（HD-MTX）治疗原发性中枢神经系统淋巴瘤（PCNSL）的最佳方案。
方法
我们检索了8个数据库，包括PubMed、EMBASE、Cochrane图书馆、WOS、Epistemonikos、中国知网、万方数据库和中国生物医学文献数据库，并筛选出关于PCNSL的临床试验。我们的分析共纳入37项研究，包括6项随机对照试验和31项单臂临床研究。
结果
分析37项临床研究的数据后，我们发现低剂量（<3 g/m²）、中剂量（3-5 g/m²）和高剂量（>5 g/m²）甲氨蝶呤（MTX）的汇总总缓解率（ORR）分别为0.78、0.80和0.80。低剂量、中剂量和高剂量MTX的汇总2年总生存率（OS）分别为52%、60%和71%。接受<5个周期MTX治疗的患者的ORR、完全缓解（CR）和2年OS分别为79%、41%和59%，而接受>5个周期MTX治疗的PCNSL患者的ORR、CR和2年OS分别为81%、54%和64%。MTX、双联疗法、三联疗法、四联疗法和多联疗法的汇总ORR分别为71%、70%、81%、85%和80%。不同药物组合数量的汇总2年OS分别为59%、52%、66%、63%和60%。在基于MTX的化疗中添加阿糖胞苷可提高CR，尽管在OS方面未观察到统计学显著差异。在治疗方案中添加利妥昔单抗可改善患者的无进展生存期，而不影响治疗反应或OS。
结论
基于本研究的结果，MTX的治疗策略与PCNSL患者的预后和疗效反应相关。结果表明，目前推荐的3.5 g/m² HD-MTX剂量足以使PCNSL获得良好的治疗反应和预后。当MTX治疗周期数增加时，PCNSL患者的治疗效果和预后得到改善。接受基于MTX的三联联合方案治疗的患者具有更好的ORR和CR。尽管HD-MTX通常耐受性良好，但对于包括阿糖胞苷在内的多联疗法的使用仍需谨慎，以预防潜在的急性毒性。
Zotero 插件