外周T细胞淋巴瘤的治疗与预后

发布时间：2018-05-31 07:09

本文选题：ALK阴性间变大细胞淋巴瘤 + 外周T细胞淋巴瘤非特指型　；参考：《北京协和医学院》2017年博士论文

【摘要】：第一部分ALK阴性间变大细胞淋巴瘤与外周T细胞淋巴瘤非特指型的临床差异研究目的:比较ALK阴性间变大细胞淋巴瘤(ALK-ALCL)与外周T细胞淋巴瘤非特指型(PTCL-NOS)在临床表现、近期疗效及预后方面的差异。材料与方法:回顾性分析中国医学科学院肿瘤医院诊治的48例ALK-ALCL及119例PTCL-NOS患者。前者Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者分别有14例(29%)、16例(33%)、12例(25%)和6例(13%),后者Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者分别有19例(16%)、31例(26%)、33例(28%)和36例(30%)。早期患者多接受化疗联合受累野放疗,晚期患者以化疗为主。研究结果:PTCL-NOS患者中,一般状态评分差者(ECOG评分≥2)、伴结外器官受累患者、Ⅲ-Ⅳ期患者、国际预后评分(IPI)及外周T细胞淋巴瘤非特指型预后评分(PIT)评为中高危组的患者较ALK-ALCL患者更为多见。ALK-ALCL化疗后完全缓解(CR)率为47.9%,显著优于PTCL-NOS的31.0%(P = 0.041)。生存分析结果显示,ALK-ALCL患者的5年总生存率(OS)及无进展生存率(PFS)分别为57.9%和43.8%,而PTCL-NOS患者的5年OS及PFS分别为23.9%和13.8%(OS:P=0.002;PFS:P=0.001)。早期患者中,ALK-ALCL患者的预后仍明显优于PTCL-NOS患者。晚期患者中,两者的预后均很差,OS和PFS比较未见明显差异。结论:与ALK-ALCL相比,PTCL-NOS的临床表现更具侵袭性,近期疗效及预后更差,支持两者是不同的疾病实体。第二部分早期外周T细胞淋巴瘤非特指型的治疗及预后分析研究目的:分析早期外周T细胞淋巴瘤非特指型不同治疗方案的疗效及预后。材料与方法:回顾性分析1998年1月至2014年12月中国医学科学院肿瘤医院收治的50例早期外周T细胞淋巴瘤非特指型患者,其中Ⅰ期19例(38%),Ⅱ期31例(62%)。31例接受化疗联合放疗或单纯放疗(放疗±化疗组),18例仅接受化疗(单纯化疗组),1例局部手术治疗。化疗方案以蒽环类方案为主,其中CHOP方案(环磷酰胺+长春碱+阿霉素+强的松)21例,CHOPE方案(CHOP联合依托泊苷)16例。运用SPSS 21.0软件进行统计分析,Kaplan-Meier法绘制生存曲线,生存曲线间比较采用Log-rank检验。研究结果:全组患者的客观反应率和完全缓解率为75.5%和61.2%,5年生存率(OS)、5年肿瘤特异性生存率(CSS)和5年无进展生存率(PFS)分别为32.0%、34.9%和27.6%。放疗±化疗组的5年CSS和PFS分别为44%和41%,单纯化疗组的5年CSS 和 PFS 均为 13%(CSS:P=0.045;PFS:P=0.044)。CHOEP 方案化疗组较CHOP方案化疗组血清LDH水平更高(P=0.001)、一般状况更差(P=0.036)。两组比较,PFS和OS均无明显差异。CHOEP方案化疗组的3年PFS和OS分别为28.3%和41.4%;CHOP方案化疗组的3年PFS和OS分别为29.7%(P=0.986)和43.0%(P=0.521)。结论:早期外周T细胞淋巴瘤非特指型传统化疗疗效欠佳,辅助放疗可改善患者的预后。第三部分早期结外鼻型NK/T细胞淋巴瘤化疗完全缓解后放疗的价值研究目的:研究早期结外鼻型NK/T细胞淋巴瘤化疗完全缓解后巩固放疗的作用。材料与方法:回顾性分析2000-2013年全国10家肿瘤中心收治的217例早期结外鼻型NK/T细胞淋巴瘤患者,所有病例均以化疗为初始治疗,疗效评价为完全缓解。其中160例接受序贯放疗(化疗+放疗组),57例未接受放疗(单纯化疗组)。采用倾向配比分析平衡两治疗组间差异。研究终点包括总生存(OS)、无进展生存(PFS)、局部区域失败(LRF)及系统失败(SF)。OS和PFS分析采用Kaplan-Meier法及Cox风险比例回归;LRF及SF分析采用竞争风险分析。研究结果:单纯化疗组的5年PFS和OS分别为37.9%和58.8%;巩固放疗显著提高了 PFS(5 年 PFS:70.0%,P0.001)和 OS(5 年 OS:79.1%,P = 0.011)。采用PSM控制混杂因素后,化疗+放疗组的OS和PFS仍优于单纯化疗组。亚组分析结果显示,不同化疗方案及化疗周期组中化疗+放疗组的预后均优于单纯化疗组。对于接受含左旋门冬酰胺酶方案化疗的患者(n = 47)及化疗≥4周期的患者(n =170),放疗均能显著改善PFS及OS。失败模式分析结果示,单纯化疗组疾病失败率高达57.9%(33/57),以LRF为主(25/57,43.9%)。相比单纯化疗组,化疗+放疗组显著降低了 LRF(5年累计LRF:45.1%vs.14.4%,P0.001)及SF(5年累计SF:33.0%vs.20.1%,P=0.046)。配比前后多因素分析结果均显示,放疗是OS、PFS、LRF及SF的独立预后因素。结论:早期结外鼻型NK/T细胞淋巴瘤单纯化疗后完全缓解患者疾病失败率高,预后差。放疗可显著改善疾病控制及远期生存,是早期结外鼻型NK/T细胞淋巴瘤一线治疗不可或缺的治疗手段。
[Abstract]:Part 1 clinical differences of ALK negative intercellular large cell lymphoma and peripheral T cell lymphoma Objective: To compare the clinical manifestations, short-term efficacy and prognosis of ALK negative large cell lymphoma (ALK-ALCL) and peripheral T cell lymphoma (PTCL-NOS). Materials and methods: a retrospective analysis of Chinese Medicine 48 cases of ALK-ALCL and 119 patients with PTCL-NOS were diagnosed and treated by the Cancer Hospital of the academic institute. The former I, II, III and IV had 14 (29%), 16 (33%), 12 (25%) and 6 (13%), and 19 (16%) and 31 cases (16%) in stage I, II, III and IV, respectively. In patients with PTCL-NOS, the patients with poor general state score (ECOG score > 2), patients with external organ involvement, patients with stage III to IV, international prognosis score (IPI) and peripheral T cell lymphoma non special index prognostic score (PIT) were more likely than those in ALK-ALCL patients to be more likely to be treated with.ALK-ALCL chemotherapy. The rate of CR was 47.9%, significantly better than that of PTCL-NOS (P = 0.041). Survival analysis showed that the 5 year total survival rate (OS) and progression free survival (PFS) of ALK-ALCL patients were 57.9% and 43.8% respectively, while 5 years in PTCL-NOS patients were 23.9% and 13.8% (OS:P= 0.002; PFS:P=0.001). The prognosis of ALK-ALCL patients was still obvious in early patients. Superior to PTCL-NOS patients. In advanced patients, the prognosis of both of them was poor, and there was no significant difference between OS and PFS. Conclusion: compared with ALK-ALCL, the clinical manifestation of PTCL-NOS is more aggressive, the short-term effect and prognosis are worse, and the two are different disease entities. The treatment and prognosis of the non special type of early peripheral T cell lymphoma in the second part of the patients are divided. Objective: to analyze the effect and prognosis of different treatment schemes for early peripheral T cell lymphoma. Materials and methods: retrospective analysis of 50 cases of early peripheral T cell lymphoma of non special finger patients admitted from January 1998 to December 2014 in the Cancer Hospital of the Chinese Academy of Medical Sciences, including 19 cases (38%) in stage I, 31 cases in stage II (62%).31 cases. Chemotherapy combined with radiotherapy or radiotherapy alone (radiotherapy + chemotherapy group), 18 patients received only chemotherapy (simple chemotherapy group) and 1 cases of local surgery. The chemotherapy regimen was mainly anthracycline regimen, including 21 cases of CHOP (cyclophosphamide + Changchun alkali + adriamycin + prednisone), 16 cases (CHOP combined with etoposide) and SPSS 21 software for statistical analysis. Analysis, the Kaplan-Meier method was used to draw the survival curve, and the survival curve was compared with the Log-rank test. The results showed that the objective response rate and complete remission rate of the whole group were 75.5% and 61.2%, the 5 year survival rate (OS), the 5 year tumor specific survival rate (CSS) and the 5 year progression free survival rate (PFS) were 32%, 34.9% and 27.6%. radiotherapy group 5 year CSS and P, respectively. The FS was 44% and 41% respectively. The 5 year CSS and PFS in the chemotherapy group were 13% (CSS:P=0.045; PFS:P=0.044), and the serum LDH level was higher (P=0.001) than the CHOP regimen chemotherapy group (P=0.001), and the general condition was worse (P=0.036). The two groups compared, PFS and OS were 28.3% and 41.4% respectively, and 28.3% and 41.4% respectively. The 3 year PFS and OS of the case chemotherapy group were 29.7% (P=0.986) and 43% (P=0.521). Conclusion: early peripheral T cell lymphoma of non special type traditional chemotherapy is not good, adjuvant radiotherapy can improve the prognosis of patients. The value of the third part of early nasal type NK/T cell lymphoma chemotherapy after complete slow solution radiotherapy: the study of early extranodal nasal type The effect of radiotherapy on NK/T cell lymphoma after complete remission. Materials and methods: retrospective analysis of 217 cases of early extranodal NK/T cell lymphoma in 10 cancer centers in 2000-2013 years. All cases were treated with chemotherapy and the curative effect was completely remitted. 160 cases received sequential radiotherapy (chemotherapy plus radiotherapy). Group), 57 cases were not treated with radiotherapy (simple chemotherapy group). The difference between the two treatment groups was analyzed with the tendency ratio analysis. The end point included total survival (OS), progression free survival (PFS), local regional failure (LRF) and system failure (SF).OS and PFS analysis using Kaplan-Meier and Cox risk ratio regression; LRF and SF analysis using competitive risk analysis. Results: the 5 year PFS and OS in the simple chemotherapy group were 37.9% and 58.8%, respectively, and the consolidation radiotherapy significantly improved PFS (5 year PFS:70.0%, P0.001) and OS (5 year OS:79.1%, P = 0.011). The OS and PFS of chemotherapy plus radiotherapy group were still superior to those in the chemotherapy group. The subgroup analysis showed that the chemotherapy plus chemotherapy cycle group was chemotherapy +. The prognosis of the radiotherapy group was better than that in the simple chemotherapy group. For patients receiving L-asparaginase chemotherapy (n = 47) and patients with chemotherapy more than 4 cycles (n =170), radiotherapy could significantly improve the failure mode analysis of PFS and OS.. The failure rate of the simple chemotherapy group was 57.9% (33/57), LRF was the main (25/57,43.9%). Compared with the simple chemotherapy, the chemotherapy group was compared with the simple chemotherapy. Group, chemotherapy plus radiotherapy group significantly reduced LRF (5 years LRF:45.1%vs.14.4%, P0.001) and SF (5 years SF:33.0%vs.20.1%, P=0.046). The results of multiple factors analysis showed that radiotherapy was an independent prognostic factor of OS, PFS, LRF and SF. Conclusion: early nasal type NK/ T cell lymphoma was completely relieved of the rate of disease failure after chemotherapy. Radiotherapy can significantly improve disease control and long-term survival. It is an indispensable treatment for first-line treatment of extranodal naso NK/T cell lymphoma.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R733.1

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