大剂量甲氨蝶呤和替莫唑胺与利妥昔单抗联合治疗原发性中枢神经系统淋巴瘤患者的临床疗效

Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma

目的:探讨大剂量甲氨蝶呤(HD-MTX)和替莫唑胺(TMZ)与利妥昔单抗(R)联合治疗原发性中枢神经系统淋巴瘤(PCNSL)患者的临床疗效。方法:收集2010年2月至2017年5月于广东省人民医院诊治的PCNSL患者的临床资料。首先给予患者6-8个周期的MTX(3.5 g/m^(2))进行诱导治疗,再给予12个周期的TMZ(150 mg/m^(2))进行维持治疗。诱导治疗前一天,根据患者经济情况,给予R 375 mg/m^(2)。采用回顾性队列研究的方法,对接受HD-MTX+TMZ治疗的患者以及HD-MTX+TMZ+R治疗的患者进行疗效和预后的生存分析。结果:共有42例患者纳入研究,HD-MTX+TMZ组17例,中位无进展生存期和总生存期分别为7.3和34.7个月;HD-MTX+TMZ+R组25例,中位无进展生存期和总生存期分别为56.7个月和未达到。此外,接受TMZ维持治疗和只进行积极监测的患者之间的中位生存期无显著性差异。在诱导期所有患者均出现1-2级恶心和呕吐,而在巩固治疗期,所有患者未观察到3/4级毒性。结论:HD-MTX+TMZ+R联合治疗PCNSL患者的近期疗效确切,有效性尚可,毒副反应比较轻微,患者可耐受。

Objective: To investigate the clinical efficacy of high dose methotrexate(HD-MTX), temozolomide(TMZ),and rituximab(R) in the treatment of patients with primary central nervous system lymphoma(PCNSL). Methods:Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People’s Hospital from February2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX(3.5 g/m^(2)) for induction treatment,and then 12 cycles of TMZ(150 mg/m^(2)) for maintenance treatment. The day before induction treatment, patients were given rituximab 375 mg/m^(2) according to their economic status. A retrospective cohort study was performed on patients receiving HD-MTX+TMZ or HD-MTX+TMZ+R to analyze the efficacy and survival. Results: There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed. Conclusion: The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite shortterm effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.