Clinical impact of serum survivin positivity and tissue expression of EBV-encoded RNA in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

Abstract

Survivin is an inhibitor of apoptosis and is upregulated by Epstein–Barr virus (EBV) latent genes. Given the frequent association of EBV with lymphoid malignancies, survivin is expected to have prognostic value in diffuse large B-cell lymphoma (DLBCL). Thus, we measured the pretreatment serum level of survivin in DLBCL patients and analyzed its association with survival outcome and EBV status, as represented by EBV-encoded RNA (EBER) in DLBCL. Pretreatment serum survivin level was measured in patients registered in a prospective cohort study (n = 210), and serum survivin-positivity was defined as any detectable level of survivin. EBV status was determined using EBER in situ hybridization, and EBER-positivity was defined as 20% of examined cells showing nuclear positivity. Mean serum survivin level was higher in patients with relapsed or refractory disease than with responsive disease (59.89 pg/mL versus 17.34 pg/mL, P = 0.041). Serum survivin-positive patients had worse overall and progression-free survival (P = 0.023 and 0.022, respectively). Serum survivin positivity was associated with unfavorable characteristics including stage. In patients with non-germinal center B-cell type DLBCL, serum survivin-positive patients also had significantly worse survival than serum survivin-negative patients (P < 0.001). EBER-positivity was found in 6.7% (14/210) of patients, and EBER-positive patients had worse survival (P < 0.05). Patients having concomitant positivity for serum survivin and EBER expression (2.8%, 6/210) showed extremely poor prognosis. In the present era of rituximab in DLBCL, DLBCL with serum survivin positivity showed adverse clinical features and followed worse clinical course, especially in non-GCB subtype DLBCL. EBER-positivity was still associated with worse outcomes in DLBCL.

EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2018 update on diagnosis, risk‐stratification and management

“…These findings were similar to the response and survival rates in EBV‐negative DLBCL patients. However, in other more recent Asian studies, the use of R‐CHOP was associated with poorer survival outcomes in patients with EBV+ DLBCL, NOS, when compared with EBV‐negative DLBCL patients . An early study reported EBV+ status was less frequent in DLBCL patients younger than 50 than in older than 50 (7 vs 9%, respectively) and had no impact on PFS and OS when treated with R‐CHOP …”

“…Higher levels were seen in EBV+ than in EBV‐negative DLBCL cases (19 vs. 5%, respectively). High serum survivin levels and were associated with poor outcomes …”

New developments in the pathology of malignant lymphoma: a review of the literature published from January to April 2017

“…GLUT1 expression in HRS cells was not associated with overall survival or event-free survival although in the subgroup with high stage, it was associated with better event-free survival. Hong et al [ 35 ] measured the pretreatment serum level of survivin in 210 DLBCL patients and analyzed its association with survival outcome and EBV status, as represented by EBV-encoded RNA (EBER) in DLBCL. Mean serum survivin level was higher in patients with relapsed or refractory disease than with responsive disease.…”

Epstein-Barr virus exanthem in an adult patient with myelodysplastic syndrome

“…The EBV LMP‐1 protein has oncogenic effects both in B cells and epithelial cells. In immunocompromised patients, abundant LMP‐1 expression is visible in B cells prior to onset of lymphoproliferative diseases or leukaemia . EBER positivity was recently associated with worse outcomes in diffuse large B‐cell lymphoma .…”

“…In immunocompromised patients, abundant LMP‐1 expression is visible in B cells prior to onset of lymphoproliferative diseases or leukaemia . EBER positivity was recently associated with worse outcomes in diffuse large B‐cell lymphoma . Currently, there are no approved therapeutic agents to treat systemic reactivation of EBV in immunocompromised patients.…”