Differential Reactivation of Cytomegalovirus and Epstein-Barr Virus in Patients with B Cell Lymphoma

Although cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are considered latent viruses, their reactivation occurs in immunosuppressed conditions. We previously reported that CMV and EBV are reactivated in patients receiving immunosuppressive therapy and/or chemotherapy. This retrospective, single-center study aimed to determine the frequency of viral reactivation and clinical characteristics of patients with B cell lymphoma (B-ML) receiving chemotherapy. Twenty-four patients (mean age 73 years, range 40-87 years; male-to-female ratio, 15:9) with diffuse large B cell lymphoma (n = 15), follicular lymphoma (n = 8), or mantle cell lymphoma (n = 1) were enrolled. Serum CMV and EBV DNA levels were analyzed using quantitative real-time polymerase chain reaction in patients with B-ML receiving chemotherapy. We determined the cumulative reactivation of each virus and analyzed the relationship between viral reactivation and clinical characteristics. Three patients experienced relapse or refractory (R/R) disease and the others had de novo lymphomas. The frequencies of CMV and EBV reactivations were 54.2% and 37.5%, respectively. CMV reactivation occurred significantly earlier during chemotherapy courses in R/R patients than in de novo patients (p = 0.0038), while EBV reactivation was frequently found before treatment. Baseline serum levels of soluble interleukin-2 receptor were higher (4318.0 vs. 981.1 U/mL, p = 0.010) and hemoglobin levels were lower (11.1 vs. 13.0 g/dL, p = 0.0038) in patients with EBV reactivation than in those without reactivation. These findings were not observed in patients with CMV reactivation. CMV reactivation was associated with iatrogenic immunosuppression, whereas EBV reactivation was related to immunosuppression by lymphoma, indicating that the mechanisms of these viral reactivations differed.