The Relationship Of Epstein-Barr Virus Infection And Multiple Myeloma And Its Impact On Clinical Characteristics And Prognosis

Objective: While there are many studies have shown Epstein-Barr virus(EBV)is associated with lymphoma,nasopharyngeal carcinoma and some benign or malignant lymphoproliogenic diseases,the study between EBV and multiple myeloma(MM)are uncommon.The aim of this study was to evaluate the relationship of EBV infection and multiple myeloma and its impact on clinical characteristics and prognosis.Methods: 1.Fresh peripheral blood mononuclear cells(PBMCs)from 139 MM patients who had been diagnosed and treated from January 2010 to May 2018 and 50 PBMCs samples from healthy donors were obtained.Polymerase chain reaction(PCR)was carried out for detection of EBV-DNA.2.The DNA expression level was dynamically monitored for six courses in pretreatment with high expression of EBV-DNA MM patients.Results: 1.The results indicated a significantly higher EBV-DNA concentration among 139 MM patients compared with healthy controls(P=0.008);2.Correlation analysis showed that the expression of EBV-DNA was positively correlated with the serum free light chain ratio(s FLCR)(rs=0.237;P=0.029)and disease PD/relapse(rs=0.285;P=0.008);3.In EBV-DNA high-expression MM patients,EBV-DNA concentration for patients with s FLCR?100 was higher than that of patients with s FLCR<100(P=0.043),EBV-DNA concentration was higher in patients with disease PD/relapse than those without disease PD/relapse(P=0.021);4.In univariate analysis,the progress free survival(PFS)was inferior in MM patients with high expression of EBV-DNA(?2=3.606,P=0.046),high LDH(?2= 5.738,P=0.014),and high-risk according to m SMART(?2= 11.691,P=0.003)and IMWG(?2=10.211,P=0.001),stage III according to R-ISS staging(?2= 5.477,P=0.048),extramedullary disease(?2=4.434,P=0.035),and genetic changes(?2=11.127,P=0.001);5.In multivariate analysis,LDH(HR0.404,95%CI 0.146-1.116,P=0.048),poor karyotype(HR0.295,95%CI 0.105-0.825,P =0.020),R-ISS staging(HR0.462,95%CI 0.192-1.111,P=0.045)and m SMART(HR2.478,95%CI 1.006-6.103,P=0.049)were independent prognostic factors for PFS;6.The DNA expression level was dynamically monitored for six courses in 20 pretreatment with high expression of EBV-DNA MM patients.Patients with EBV-DNA copies was still higher than 5000/ml after 3 cycles of chemotherapy had lower PFS than those whose EBV-DNA copies was lower than 5000/ml after 3 cycles of chemotherapy(P<0.001).Conclusion: Taken together,our studies suggest that an association exists between EBV infection and clinical characteristics of MM patients,and EBV infection appears to have a slight impact on the prognosis of MM.Regarding the dynamic changes in copy number of elevated EBV DNA,the transformation from positive to negative after cycle 3 with chemotherapy may have the most capacity to distinguish a superior from an inferior outcome.However,the results require further validation in other independent prospective MM cohorts.