Clinical Characteristics And Prognosis Of Diffuse Large B-Cell Lymphoma With Hepatitis B Virus Infection

Background and PurposeLymphoma is a lymphatic hematopoietic tumor of unknown etiology.Its incidence has been increasing year by year.It can be divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma according to the pathological tissue type.Diffuse large B-cell lymphoma is one of the most common types of non-Hodgkin's lymphoma(NHL),accounting for 35%-40%of NHL.DLBCL has the features of high heterogeneity,high degree of malignancy and poor prognosis.The standard chemotherapy regimens mainly compromise CHOP or R-CHOP.Hepatitis B virus is a spherical double-stranded circular DNA virus whose infection is a global issue.And China is a highly endemic area of HBV infection.The HBV infection rate in China is higher than in developed countries such as the United States,Europe and Japan.Therefore,it is of practical significance to dig the relationship between HBV infection and DLBCL.Many studies have found that people with HBV infection are more likely to develop lymphoma.At the same time,patients with B-cell non-Hodgkin's lymphoma had a higher HBV infection rate than T-cell non-Hodgkin's lymphoma,especially DLBCL.Drugs for treating DLBCL might cause reactivation of HBV,abnormal liver function,liver failure,etc.That would affect the treatment process and threaten the life and health of patients.Therefore,the preventive application of antiviral drugs has a certain effect on reducing HBV-DNA replication in serum and preventing HBV reactivation.However,the effects of HBV infection on the efficacy and prognosis of DLBCL patients which had been reported by research centers around the world were different.In this study,the clinical characteristics,treatment effects,and survival prognosis of DLBCL patients with and without HBV infection were explored.We wanted to clarify the relationship between HBV infection and DLBCL to improve the prevention and treatment of DLBCL patients with HBV infection.Materials and MethodsWe retrospectively analyzed all patients with diffuse large B-cell lymphoma who were admitted to the First Affiliated Hospital of Zhengzhou University from January 1,2012 to December 31,2017.The pathological tissues were diagnosed by at least 2 pathologists in the pathology department of our hospital.227 patients who met the inclusion criteria were divided into HBV infected group and non-HBV infected group.The non-HBV infected group included total negative group and only HBsAb(+)group.The HBV infected group could be divided into the current infection group[HBsAg(+)]and the previous infection group[HBsAg(-)HBcAb(+)].The HBV previous infection group[(HBsAg(-)HBcAb(+)]could be further divided into.two subgroups:HBsAg(-)HBcAb(+)HBsAb(-)group and HBsAg(-)HBcAb(+)HBsAb(+)group.We collected clinical characteristics of patients,including:gender,age,pathological classification,expression of c-myc,bcl-2 and bcl-6,proliferation index(Ki-67),clinical stage(Ann Arbor stage),time of diagnosis of disease,tumor origin,tumor location and number of lesions,whether there was liver invasion,liver function indicators before and during chemotherapy,whether there was spleen invasion,international prognostic index score,physical status score,serum ?2 microglobulin level,serum lactate dehydrogenase level and HBV reactivation.All patients were treated with CHOP or R-CHOP regimen.Patients were evaluated every two cycles during treatment,and the outcomes can be divided into:complete remission,partial remission,progressive disease and stable disease.Through the follow-up,the patient's living status and other data were obtained to determine the patient's overall survival time and disease progression time.Statistical analysis was performed using SPSS 23.0 software.The t-test,?2 test and rank sum test were used to compare the quantitative variable,qualitative data and grade data respectively.The Kaplan-Meier method and Log-rank test were applied to the survival analysis.Univariate analysis was done by Kaplan Meier method.And multivariate analysis was done by using the Cox proportional hazards model.The difference was statistically significant at P<0.05.ResultsAmong the 227 patients with DLBCL,121 had no HBV infection.75 patients'tests for hepatitis B patients were all negative,and only 46 patients were positive for HBsAb.There were 26 HBsAg(+)patients.A total of 80 patients who previously infected with HBV were HBsAg(-)and HBcAb(+).Among these 80 patients,57 were HBsAg(-)HBcAb(+)HBsAb(+)patients and 23 were HBsAg(-)HBcAb(+)HBsAb(-)patients.Among all patients,16 were positive for serum HBV-DNA before treatment.The median age in the HBV infected group was older than in the non-HBV infected group.The median age in HBV infected group was 60 years old(22-83 years),and it in the non-HBV infected group was 55 years old(8-81 years).There was a statistically significant difference between the two groups,60 years or older and less than 60 years old(?2=3.942,P=0.047).The spleen involvement was more common in the HBV infected group than in the non-HBV infected group(?2=4.518,P=0.034).There were no significant differences in gender,the number of extranodal organs involved,liver involvement,clinical stage,IPI score,serum LDH level,serum?2 microglobulin level,liver function abnormality before and during chemotherapy,and expression of c-myc,bcl-2 and bcl-6.There were 16 patients with HBV-DNA replication above normal levels before treatment,and 15 of them were HBsAg-positive.The other one patient was HBsAg-negative but HBcAb-positive.9 patients with previous HBV infection were reactivated during treatment.And seven of them received rituximab during chemotherapy.The CR,PR,SD,and PD in the non-HBV infected group were 77(63.6%),22(18.2%),3(2.5%),and 19(15.7%)cases,respectively.Among the patients who were in the HBV infected group,the CR,PR,SD,and PD were 56(52.8%),17(16.0%),2(1.9%),and 31(29.2%)cases separately.There was a statistical difference in the treatment effect between the two groups(x2=-2.052,P=0.04).The rate of remission in the non-HBV infected group was better than that in the HBV infected group,which was statistically different(81.8%vs.68.8%,?2=5.162,P=0.023).The HBV infected group was further divided into two groups:the current infection group[HBsAg(+)]and the previous infection group[HBsAg(-)HBcAb(+)],with 26 and 80 patients,severally.There were 10(38.5%),4(15.4%),1(3.8%),and 11(42.3%)patients gaining CR,PR,SD,and PD in the current infection group.And 14 cases(53.9%)achieved objective remission.In the HBV previous infection group,46(57.5%),13(16.3%),1(1.3%),and 20(25.0%)patients achieved CR,PR,SD,and PD.There were 59 cases(73.8%)achieved objective remission.No statistically significant differences were between the two groups(?2=-1.867,P=0.063;?2=3.626,P=0.057).Patients with HBV previous infection can be further divided into HBsAg(-)HBcAb(+)HBsAb(-)group,23 cases,and HBsAg(-)HBcAb(+)HBsAb(+)group,57 cases.And 13 cases(56.5%),2 cases(8.7%),0 cases(0.0%),and 8 cases(34.8%)of DLBCL patients got CR,PR,SD and PD in the former group.There were 33 cases(57.9%),11 cases(19.3%),1 case(1.8%),and 12 cases(21.1%)achieving CR,PR,SD,and PD in the latter group.There was no significant difference in the therapeutic effects between the two groups(?2=-0.526,P=0.599).The ORRs of the two groups were 65.2%and 77.2%,respectively,with no statistical difference(?2=1.214,P=0.271).A total of 121 patients without HBV infection were divided into the total negative group,75 cases,and only HBsAb(+)group,46 cases.There was no significant difference between the two groups(?2=-0.720,P=0.472).The ORR of the total negative group and the only HBsAb(+)group were 80.0%and 84.7%,respectively.The difference was not statistically significant(?2=0.438,P=0.508).In the total negative group,there were 44 cases,16 cases,3 cases,and 12 cases of CR,PR,SD,and PD,respectively.The CR,PR,SD,and PD rates were 58.7%,21.3%,4.0%,and 16.0%.In the only HBsAb(+)group,there were 33 cases,6 cases,0 case,and 7 cases of CR,PR,SD,and PD.The CR,PR,SD,and PD rates were 71.7%,13.0%,0.0%,and 15.2%,respectively.The progression free survival time was(61.9±2.4)months in the non-HBV infected group,and the 5 year PFS rate was 82.9%.While the PFS of the HBV infected group was(46.0±2.7)months,and the 5 year PFS rate was 57.8%.The difference was statistically significant(x2=5.325,P=0.021).Similarly,the overall survival was(67.1±2.0)months in the non-HBV infected group,and the 5 year OS rate was 89.9%.The OS of the HBV infected group was(61.9±3.0)months,and the 5 year OS rate was 75.0%.The difference was statistically significant(x2=5.619,P=0.018).Although the prognosis of the HBV previous infection group was better than that of the HBV current infection group,there was no significant difference in PFS and OS between the two groups((38.8±5.2)m vs.(48.2±3.0)m,50.6%vs.56.5%,?2=1.588,P=0.208;(45.0±4.9)m vs.(64.5±3.2)m,62.2%vs.79.5%,x2=2.280,P=0.131).The PFS of HBsAg(-)HBcAb(+)HBsAb(-)group was(44.4±5.5)months,the 5 year PFS rate was 57.4%;the PFS of HBsAg(-)HBcAb(+)HBsAb(+)group was(50.8±3.4)months,the 5 year PFS rate was 59.0%.There was no statistical difference between the groups(?2=0.787,P=0.375).The HBsAg(-)HBcAb(+)HBsAb(-)group had an OS of(66.6±5.5)months,the 5 year OS rate was 79.2%.And the HBsAg(-)HBcAb(+)HBsAb(+)group had an OS of(60.7±3.7)months,the 5 year OS rate was 80.2%.There was no statistical difference between the two groups(?2=0.280,P=0.596).There was no significant difference in PFS and OS between the total negative group and only HBsAb(+)group.((62.4±2.9)m vs.(58.6±4.7)m,84.4%vs.77.8%,?2=0.006,P=0.937;(69.0±1.9)m vs.(61.2±5.0)m,93.6%vs.80.2%,?2=1.034,P=0.309).Age>60 years old,male,medium and high risk of IPI,liver involvement,spleen involvement,number of extranodal involvement>1,stage ?/?,abnormal liver function before chemotherapy,abnormal liver function during chemotherapy and other factors were included in the Cox proportional hazard model for multivariate analysis.Pre-chemotherapy liver function abnormalities(HR=2.386(1.009-5.641),P=0.048)was independent prognostic factor for DLBCL patients with HBV infection.Conclusions(1)The age of HBV infected group was older than,the non-HBV infected group.And spleen involvement was more common in the HBV infected group.Liver dysfunction before chemotherapy is independent prognostic factor for DLBCL patients with HBV infection.(2)The short-term and long-term effects of the HBV infection group were worse than non-HBV infection group.