弥漫大B细胞淋巴瘤合并HBV感染的临床特点及预后分析

发布时间：2019-03-21 14:17

【摘要】：目的:弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)是成人非霍奇金淋巴瘤(non Hodgkin lymphoma,NHL)中最常见的亚型,约占成人NHL的30~40%,目前许多研究证实NHL的发生与乙型肝炎病毒(hepatitis B virus,HBV)感染有一定关系。我国为HBV感染的高流行区,关于感染HBV是否影响DLBCL患者的疾病转归及预后的报道较为少见。本研究对天津市三所三级甲等医院2009年6月至2014年1月初治的、经病理学或组织学确诊的DLBCL患者共521例进行分析,从中筛选出符合纳入标准的DLBCL患者共235例,旨在通过分析伴或不伴HBV感染的DLBCL患者的临床特征、肝功能损害及预后情况,以探讨HBV感染与DLBCL的关系。方法:回顾性分析天津市三所三级甲等医院(包括天津医科大学肿瘤医院、天津市南开医院及天津市人民医院)2009年6月至2014年1月初治的、经病理学或组织学确诊的DLBCL患者共521例,其中乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)阳性98例,占18.8%。从中筛选出符合以下纳入标准的DLBCL患者共235例,将其分为HBsAg阳性组(n=76)和HBsAg阴性组(n=159)。所有患者均接受CHOP样方案(环磷酰胺、蒽环类、长春碱及泼尼松)或R-CHOP样方案(美罗华联合CHOP样方案)治疗,化疗周期数≥4。肝功能损害者给予还原型谷胱甘肽、异甘草酸美、双环醇等保肝降酶治疗,联合或不联合抗乙肝病毒治疗。收集两组临床特点包括:年龄、性别、体能评分、临床分期、结外受累数目、骨髓受累、脾脏受累、肝脏受累、乳酸脱氢酶(lactate dehydrogenase,LDH)、β2微球蛋白(β2-microglobulin,β2-MG)、IPI评分、B症状、病理分型、化疗方案、联合放疗、近期疗效、化疗前肝损害、化疗期间肝损害。电话随访患者的疾病及生存情况,随访截止日期为2015年1月1日。应用SPSS 17.0软件进行统计学分析。各组生存率用log-rank检验。生存分析采Kaplan-Meier法,多因素分析采用Cox比例风险模型。P0.05表示差异有统计学意义。结果:1、521例DLBCL患者中HBV感染率为18.8%,我国普通人感染率为7.18%。2、hbsag阳性组与hbsag阴性组相比,hbsag阳性dlbcl患者中位发病年龄较轻(47岁vs58岁,p0.001),脾脏受累(26.3%vs15.1%,p=0.039)和肝脏受累(11.8%vs4.4%,p=0.034)较hbsag阴性患者多见,差异有统计学意义。3、hbsag阳性组与hbsag阴性组相比,hbsag阳性dlbcl患者化疗期间肝损害发生率较高(47.4%vs26.2%,p=0.001),差异均有统计学意义。4、hbsag阳性组与hbsag阴性组相比,hbsag阳性组中美罗华增加了化疗期间肝损害发生率(60.0%vs29.0%,p=0.008),差异有统计学意义;而hbsag阴性组中美罗华未增加化疗期间肝损害发生率(29.1%vs21.4%,p=0.293)。差异无统计学意义。5、hbsag阳性组与hbsag阴性组相比,hbsag阳性组hbv再激活率高于hbsag阴性组(11.8%vs2.5%,p=0.006),差异有统计学意义。6发病年龄轻、男性、临床分期晚、联合应用美罗华化疗是增加hbsag阳性与hbsag阴性两组患者hbv再激活的影响因素,但是差异无统计学意义(p0.05)。与hbsag阳性组比较,肝脏受累增加了hbsag阴性组的hbv再激活率,(75.0%vs44.4%p=0.676),但差异无统计学意义。7、hbsag阳性组中位总生存为48个月,3年生存率为64.1%;hbsag阴性组中位总生存为42个月,3年生存率为61.7%,差异无统计学意义(χ2=0.998,p=0.320);无进展时间亦无统计学意义(χ2=2.658,p=0.103)。8、采用cox回归多因素分析:hbsag阳性dlbcl患者的不良预后因素包括年龄60岁、b症状和肝脏受累。肝功能损害不影响其总生存。结论:1、dlbcl患者hbv感染率较一般人群高。hbv在dlbcl发病中可能起到一定的作用。2、hbsag阳性组与hbsag阴性组相比,hbsag阳性dlbcl患者中位发病年龄较轻、肝脾受累多见,且化疗相关性肝损害发生率较高,美罗华增加了化疗期间肝损害发生率。3、hbsag阳性组hbv再激活率高于hbsag阴性组。发病年龄轻、男性、临床分期晚、联合应用美罗华化疗有增加两组hbv再激活的可能,肝脏受累有增加hbsag阴性患者的hbv再激活的可能。4、HBsAg阳性DLBCL患者在总生存和无进展生存方面与HBsAg阴性患者无显著差异。5、对于HBsAg阳性的DLBCL患者,特别是应用美罗华联合化疗的患者,应加强预防性抗病毒及保肝治疗,减少肝功能损害的发生及HBV再激活。
[Abstract]:Objective: The diffuse large B-cell lymphoma (DLBCL) is the most common subtype in non-Hodgkin's lymphoma (NHL), accounting for 30-40% of NHL in the adult. Our country is a high-prevalence region of HBV infection, and it is rare to report whether the infection of HBV affects the outcome of the disease and the prognosis of the patients with DLBCL. In this study, a total of 521 DLBCL patients treated by pathology or histology were analyzed from June 2009 to early January 2014, and 235 cases of DLBCL patients who met the criteria were selected. To explore the relationship between HBV infection and DLBCL by analyzing the clinical features, liver function and prognosis of patients with DLBCL with or without HBV infection. Methods: A retrospective analysis of 521 cases of DLBCL from June 2009 to early January 2014, including the three-level hospitals in Tianjin, including the Cancer Hospital of Tianjin Medical University, Nankai Hospital of Tianjin and Tianjin People's Hospital (Tianjin People's Hospital) from June 2009 to early January 2014, were analyzed retrospectively. Among them,98 cases of hepatitis B surface antigen (HBsAg) were positive, accounting for 18.8%. A total of 235 DLBCL patients were screened from which the following criteria were included: HBsAg positive group (n = 76) and HBsAg negative group (n = 159). All patients were treated with the CHOP-like regimen (cyclophosphamide, cyclinoid, vinblastine and prednisone) or the R-CHOP-like protocol (combined with the CHOP-like regimen in the United States of America) and the number of chemotherapy cycles was 4. The liver function impaired can be used for the treatment of reduced glutathione, isoglycyrrhizic acid, and bicyclol and the like, and can be combined or not combined with the anti-hepatitis B virus treatment. The clinical characteristics of the two groups were: age, sex, physical ability score, clinical stage, number of external involvement, bone marrow involvement, spleen involvement, liver involvement, lactate dehydrogenase (LDH),2-microglobulin (2-microglobal in,2-MG), IPI score, B-symptom, and pathological type. Chemotherapy regimen, combined radiotherapy, short-term efficacy, pre-chemotherapy liver damage, liver damage during chemotherapy. The condition and survival of the patients were followed up by telephone, and the follow-up cutoff date was January 1,2015. The SPSS 17.0 software was used for statistical analysis. The survival rate of each group was tested with log-rank. Kaplan-Meier method was used for survival analysis, and Cox proportional risk model was used for multi-factor analysis. The difference between the two groups was statistically significant (P <0.05). Results:1. The infection rate of HBV was 18.8% in 521 patients with DLBCL and 7.18% in the normal population in our country. The median age of the hbsac-positive dclbcl-positive group was less than that of the hbsag-positive group (47 years vs 58 years, p0.001), spleen involvement (26.3% vs15.1%, p = 0.039) and liver involvement (11.8% vs4.4%, respectively). P = 0.034) was more common in the patients with hbsag than in the hbsag-negative group, and the incidence of hepatic impairment was higher in the hbsag-positive group (47.4% vs26.2%, p = 0.001) than in the hbsag-positive group. The incidence of liver damage (60.0% vs29.0%, p = 0.008) in the hbsag positive group increased the incidence of hepatic impairment during chemotherapy (29.1% vs23.4%, p = 0.293). The positive group hbv reactivation rate was higher in the hbsag positive group than in the hbsag negative group (11.8% vs2.5%, p = 0.006). The effect of hbv reactivation in hbsag-positive and hbsag-negative patients was an important factor in the combined application of merocin chemotherapy, but the difference was not significant (p0.05). Compared with the hbsag positive group, the liver involvement increased the hbv reactivation rate of the hbsag negative group (75.0% vs44.4% p = 0.676), but the difference was not statistically significant. The median overall survival in the hbsag positive group was 48 months, the 3-year survival rate was 64.1%, the median overall survival in the hbsag negative group was 42 months, and the 3-year survival rate was 61.7%. There was no statistical significance in the difference (Sup2 = 0.998, p = 0.320); there was no statistical significance (2 = 2.658, p = 0.103).8. Cox regression analysis was used to analyze the adverse prognostic factors of hbsag-positive dlbcl2, including age 60, b and liver involvement. Liver function damage does not affect its overall survival. Conclusion:1. The infection rate of hbv in the patients with dlbcl2 is higher than that of the general population. Hbv might play a role in the pathogenesis of dlbcl2. The hbv reactivation rate was higher in the hbsag positive group than in the hbsag negative group. The incidence age was light, the male and the clinical stage were late, and the combined application of the merocin chemotherapy increased the possibility of two groups of hbv reactivation, and the liver involvement had the potential to increase the hbv reactivation of the hbsag-negative patients.4. There was no significant difference between the HBsAg-positive DLBCL patients and the HBsAg-negative patients in the overall survival and non-progression-free survival. For patients with DLBCL positive for HBsAg, especially in patients with combined chemotherapy, the prevention and treatment of anti-virus and liver protection should be enhanced, and the occurrence of hepatic function and HBV reactivation should be reduced.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R733.1

【相似文献】