The Prognostic Significance Of Plasma EBV-DNA Positive In Aggressive Non-Hodgkin Lymphoma

[Objective]Many factors influenced the prognosis of lymphoma,furthermore,Epstein-Barr virus(EBV)was known to be associated with lymphoma,and the prognostic relationship between EBV-DNA and lymphoma became a hot topic.So we retrospectively analyzed the relationship between plasma EBV-DNA and prognosis of aggressive non-Hodgkin lymphoma(NHL)and investigated whether plasma EBV-DNA was a prognostic indicator of NHL.[Methods]A total of 183 newly diagnosed NHL patients were enrolled at the Hangzhou First People's Hospital from January 2008 to December 2015.The diagnostic classification standard was defined according to the 2008 WHO lymphoid tissue tumor before treatment,all patients underwent a comprehensive clinical examination,including physical examination,blood routine,biochemical examination,ultrasound,chest and abdomen and pelvic CT,bone mairow examination etc.Risk stratification was performed using Ann Arbor staging system and international prognostic index(IPI).Plasma EBV-DNA was detected in 183 patients.The relationship between plasma EBV-DNA load and different gender,age,clinical stage,IP1 score,B symptom,LDH,?2-microglobulin and pathological types were compared.The analysis of plasma EBV-DNA load and various factors used the chi square test,survival analysis were calculated using the Kaplan-Meier method,and depicted the survival curve,and survival data were using Log-rank t test.Multivariate analysis of prognostic factors was performed by COX regression analysis.All P values were two-way,P<0.05 showed significant difference.[Results]1.Among the 183 patients enrolled,male was 116 cases,female was 67 cases,The male to female ratio of cases was 1.73:1,the median patient age was 62 years(range,23-86 years),with 53.0%of patients being older than 60 years.Diffuse large B-cell lymphoma was 122 cases,peripheral T-cell lymphoma.nos was 28 cases,NK/T cell lymphoma was 22 cases,angioimmunoblastic T-cell lymphoma was 5 cases,anaplastic large cell lymphoma was 4 cases,aggressive NK cell leukemia was 2 cases.The majority patients had B symptoms(n=114)and disease stage ?-?(n=133).IPI score of 3 to 5 was 73 cases(40.0%),elevated lactate dehydrogenase(LDH)level was 94 cases(51.4%).132 patients had high level of ?2-microglobulin(>=2.0?g/l).2.Plasma EBV-DNA positive was detected before treatment in 45 of 183(24.6%)of patients with NHL.16 peripheral T-cell lymphoma,nos,13 NK/T cell lymphoma,9 diffuse large B-cell lymphoma,3 angioimmunoblastic T-cell lymphoma,2 anaplastic large cell lymphoma and 2 aggressive NK cell leukemia were plasma EBV-DNA positive.3.Patients with plasma EBV-DNA positive were more likely to have B-symptom(P<0.001),LDH level(P<0.001)and tended to be at a more advanced stage(P=0.004)in NHL.In NK/T cell lymphoma,plasma EBV-DNA positive was more likely to have B symptom(P=0.001),the high level of LDH(P<0.001),high IPI score(P=0.020).Plasma EBV-DNA positive was more likely to have B symptom(P=0.004),high clinical stage(P=0.030),high LDH level(P=0.001)in diffuse large B cell lymphoma.4.The median follow-up time for all patients was 19 months(range,1-96 months)in NH L.,70 patients died before the end of the follow-up period.Patients with plasma EBV-DNA positive showed evidently worse overall survival(OS)and progression-free survival(PFS)than negative patients(P<0.001,P<0.001)in NHL.The median follow-up time for all patients was 24 months(range,1-96 months)in DLBCL,38 patients died before the end of the follow-up period.Patients with plasma EBV-DNA positive presented inferior OS and PFS compared with plasma EBV-DNA negative(P<0.001,P<0.001)in DLBCL.The median follow-up time for all patients was 34 months(range,1-79 months)in NK/T cell lymphoma.Likewise,patients with plasma EBV-DNA positive presented inferior OS and PFS compared with plasma EBV-DNA negative(P?0.004,P:=0.007)in NK/T cell lymphoma.However there was no significant difference between plasma EBV-DNA positive and OS,PFS in peripheral T cell lymphoma.nos.The COX regression analysis showed that plasma EBV-DNA positive and B symptoms were independent prognostic factors.[Conclusions]1.Plasma EBV-DNA positive was more common in mature T and NK lymphoma.2.Plasma EBV-DNA positive was related to more advanced disease stage,presence of B symptoms and higher LDH level.3.The patients with plasma EBV-DNA positive had poor PFS and OS.4.Plasma EBV-DNA parameters demonstrated that it was an independent poor prognostic factor for OS in patients with NHL.5.Plasma EBV-DNA positive was a potential prognostic marker for diffuse large B cell lymphoma and NK/T cell lymphoma,but plasma EBV-DAN was not a prognostic indicator of peripheral T cell lymphoma.nos.