中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (12): 1194-1201.

• 论著 • 上一篇    下一篇

42例原发性中枢神经系统淋巴瘤患者预后影响因素分析

李盼盼,张 卓   

  1. 大连医科大学附属第二医院肿瘤放疗科,辽宁 大连 116023
  • 出版日期:2021-12-30 发布日期:2022-01-07
  • 通信作者: 张 卓 E-mail: 799832582@ qq.com

Analysis of prognostic factors in 42 cases of primary central nervous system lymphoma

LI Panpan, ZHANG Zhuo   

  1. Department of Radiation Oncology, the Second Affiliated Hospital of Dalian Medical University, Dalian 116023, Liaoning Province, China
  • Published:2021-12-30 Online:2022-01-07
  • Contact: ZHANG Zhuo E-mail: 799832582@ qq.com

摘要: 背景与目的:原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)是发生在脑、脊髓、脑膜或眼的罕见侵袭型非霍奇金淋巴瘤,无CNS之外的部位累及。PCNSL与其他类型淋巴瘤相比,患者生存期短,预后差,且复发率高,未经治疗的患者的中位生存期仅为3个月。近年来研究发现C-MYC、BCL-2、BCL-6、Ki-67等指标在一定程度上影响PCNSL患者预后。因此,通过分析PCNSL相关蛋白表达、治疗方式及其他临床因素对患者预后的影响, 希望为该病的临床治疗及预后评价进一步积累资料。方法:回顾性分析自2013年6月—2021年5月于大连医科大学附属第二医院治疗的42例经病理学检查明确诊断为原发性中枢神经系统弥漫大B细胞淋巴瘤患者的临床资料,包括性别、年龄、病灶数量、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分、血清乳酸脱氢酶(lactate dehydrogenase,LDH)、病灶是否累及深部脑组织、治疗方案、病理学Hans分型及C-MYC、BCL-2、BCL-6、Ki-67等生物标志物,结合随访调查,了解患者生存时间及生存状况,应用Kaplan-Meier法及log-rank检验分析影响患者无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)的预后相关因素,多因素分析采用COX回归模型。果:42例PCNSL患者中位发病年龄61岁,男女比例为1.33∶1.00,颅脑增强MRI病灶多呈均匀明显强化。所有患者均接受含有大剂量甲氨蝶呤(high-dose methotrexate,HD-MTX)方案化疗,治疗后评价完全缓解(complete response,CR)20例、部分缓解(partial response,PR)5例,疾病稳定(stable disease,SD)11例,疾病进展(progressive disease,PD)6例。中位PFS为21个月,中位OS为34个月,1年PFS率为63.7%,2年PFS率为47.0%;1年OS率为70.8%,2年OS率为55.6%。单因素分析结果显示,影响PFS的因素是HD-MTX多药联合化疗、鞘内化疗及联合利妥昔单抗。影响OS的因素是ECOG评分≥2、C-MYC(+)、BCL-2及C-MYC双表达、HD-MTX多药联合化疗、鞘内化疗及联合利妥昔单抗。多因素分析结果显示:利妥昔单抗治疗是影响PFS的独立预后因素(P=0.020),ECOG评分、利妥昔单抗是影响OS的独立预后因素(P=0.007;P=0.046)。与未接受巩固治疗的患者相比,接受巩固治疗患者的中位PFS及OS较高;进一步的亚组分析显示,自体干细胞移植(autologous stem cell transplantation,ASCT)组的中位PFS及OS较全脑放疗(whole brain radiation therapy,WBRT)组高,但差异无统计学意义。结论:PCNSL多发于中老年人,男性多于女性,影像学缺乏特异性。ECOG评分≥2与PCNSL患者较差的OS相关。C-MYC(+)、BCL-2及C-MYC双表达可作为指导危险分层的预后标志物。以HD-MTX为基础的多药联合化疗已经成为PCNSL的首选治疗手段,利妥昔单抗的应用可延长生存期。在全身化疗的基础上,联合局部鞘内化疗可以改善预后。进一步的巩固治疗主要包括ASCT及WBRT,可延长PFS及OS,ASCT可以取得与WBRT相似的疗效,且可避免WBRT的晚期神经毒性,但本研究中因样本量及随访时间的限制,未得出明确的统计学结果。

关键词: 原发性中枢神经系统淋巴瘤/PCNSL, 弥漫大B细胞淋巴瘤, 化疗, 预后

Abstract: Background and purpose: Primary central nervous system lymphoma (PCNSL) is a rare aggressive type of non-Hodgkin's lymphoma that occurs in the brain, spinal cord, meninges or eyes, without parts outside of central nervous system (CNS) involvement. Compared with other types of lymphoma, PCNSL has shorter survival time, poor prognosis and high recurrence rate. The median survival time of untreated patients is only 3 months. In recent years, studies have found that C-MYC, BCL-2, BCL-6, Ki-67 and other indicators affect the prognosis of PCNSL patients to a certain extent. Therefore, this study analyzed the effects of PCNSL-related protein expression, treatment methods and other clinical factors on the prognosis of patients, hoping to accumulate data for the clinical treatment and prognosis evaluation of the disease. Methods: In this study, we performed a retrospective analysis of the clinical data of 42 patients with primary central nervous system diffuse large B-cell lymphoma treated in the Second Affiliated Hospital of Dalian Medical University from June 2013 to May 2021, including gender, age, number of lesions, Eastern Cooperative Oncology Group (ECOG) score, serum lactate dehydrogenase (LDH), whether the lesion involves deep brain tissue, treatment plan, pathological Hans classification and C-MYC, BCL-2, BCL-6, Ki-67 and other biomarkers, combined with follow- up investigation, to understand the survival time and survival status of patients. Kaplan-Meier method and log-rank test were used to analyze the prognostic factors affecting progression-free survival (PFS) and overall survival (OS). COX regression model was used in multivariate analysis. Results: The median age of onset in 42 patients with PCNSL was 61 years, and the male to female ratio was 1.33:1.00. Most of the brain-enhanced magnetic resonance imaging (MRI) lesions showed homogeneous and obvious enhancement. All patients received chemotherapy with high-dose methotrexate (HD-MTX) regimen. After treatment, there were 20 cases of complete response (CR), 5 cases of partial remission (PR), 11 cases of stable disease (SD) and 6 cases of progressive disease (PD). The median PFS was 21 months, the median OS was 34 months, the 1-year PFS rate was 63.7%, the 2-year PFS rate was 47.0%, the 1-year OS rate was 70.8%, and the 2-year OS rate was 55.6%. Univariate analysis showed that the factors affecting PFS were HD-MTX multidrug combination chemotherapy, intrathecal chemotherapy and combined rituximab. The factors affecting OS were ECOG score ≥2, C-MYC (+), BCL-2 and C-MYC double expression, HD-MTX multidrug combination chemotherapy, intrathecal chemotherapy and combined rituximab. Multivariate analysis showed that rituximab treatment was an independent prognostic factor for PFS (P=0.020), while ECOG score and rituximab were independent prognostic factors for OS (P=0.007, P=0.046). The median PFS and OS of patients receiving consolidation therapy were higher than those of patients without consolidation therapy, and further subgroup analysis showed that the median PFS and OS of autologous stem cell transplantation (ASCT) group were higher than those of whole brain radiotherapy (WBRT) group, however there was no significant statistical difference. Conclusion: PCNSL occurs mostly in middle-aged and elderly people, more men than women without specific imaging characteristics. ECOG score ≥2 is associated with poorer OS in PCNSL patients. C-MYC (+) and dual expression of BCL-2 and C-MYC can be used as prognostic markers to guide risk stratification. HD-MTX-based multidrug combination chemotherapy has become the first choice for the treatment of PCNSL, and the application of rituximab can prolong survival. Systemic chemotherapy combined with local intrathecal chemotherapy can improve the prognosis. Further consolidation treatments mainly include ASCT and WBRT, which can prolong PFS and OS. ASCT can achieve similar curative effects as WBRT and avoid the late neurotoxicity of WBRT. However, due to the limitations of sample size and follow-up time, no clear statistical results have been obtained in this study.

Key words: Primary central nervous system lymphoma/PCNSL, Diffuse large B-cell lymphoma, Chemotherapy, Prognosis