Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia

Abstract

Human cytomegalovirus (HCMV) is a widely prevalent herpes virus which establishes a state of chronic infection. The establishment of CMV‐specific immunity controls viral reactivation and leads to the accumulation of very large numbers of virus‐specific T cells which come to dominate the immune repertoire. There is concern that this may reduce the immune response to heterologous infections and HCMV infection has been associated with reduced survival in elderly people. Patients with chronic lymphocytic leukemia (B‐CLL) suffer from a state of immune suppression but have a paradoxical increase in the magnitude of the CMV‐specific T cell and humoral immune response. As such, there is now considerable interest in how CMV infection impacts on the clinical outcome of patients with B‐CLL. Utilizing a large prospective cohort of patients with B‐CLL (n = 347) we evaluated the relationship between HCMV seropositivity and patient outcome. HCMV seropositive patients had significantly worse overall survival than HCMV negative patients in univariate analysis (HR = 2.28, 95% CI: 1.34–3.88; P = 0.002). However, CMV seropositive patients were 4 years older than seronegative donors and this survival difference was lost in multivariate modeling adjusted for age and other validated prognostic markers (P = 0.34). No significant difference was found in multivariate modeling between HCMV positive and negative patients in relation to the time to first treatment (HR = 1.12, 95% CI: 0.68–1.84; P = 0.65). These findings in a second independent cohort of 236 B‐CLL patients were validated. In conclusion no evidence that HCMV impacts on the clinical outcome of patients with B‐CLL was found. Am. J. Hematol. 91:776–781, 2016. © 2016 Wiley Periodicals, Inc.

Increased infiltration and tolerised antigen-specific CD8+ TEM cells in tumor but not peripheral blood have no impact on survival of HCMV+ glioblastoma patients

“…Nevertheless, another large prospective study of ( n = 347) leukemia patients could not demonstrate prognostic effect of HCMV status based on serology. 26 Taken together, our findings support the recent surge of interest in administering ex vivo expanded autologous antigen-specific T cells or the use of tumor lysate pulsed dendritic cells for immunotherapy against GBM. It will be important to combine these cells with immunomodulating drugs or HCMV-specific vaccines to increase T and NK cell persistence and functionality at the severely immunosuppressive tumor frontier.…”

Long-Term Ibrutinib Therapy Reverses CD8+ T Cell Exhaustion in B Cell Chronic Lymphocytic Leukaemia

“…To evaluate the latter we focused on the immune response to latent herpesviruses, which drive expanded CD8+ T cell responses in CLL in a mechanism that is thought to reflect a response to increased endogenous viral replication. EBV infection is associated with accelerated time to disease progression in CLL (15) although CMV has no known deleterious effect (16). Of interest, the magnitude of CD8+T cell CMVspecific responses increased with advanced stage disease, in line with a previous study of CD4+ immunity (data not shown) (17).…”

Increased frequency of CD4+PD‐1+HLA‐DR+ T cells is associated with disease progression in CLL

“…Cytomegalovirus can cause expansions of the CD8 + and CD4 + T‐cell subsets in CLL (Mackus et al , ; Pourgheysari et al , ), but this has little clinical impact in terms of disease outcome (Parry et al , ). It was possible that the expanded CD4 + T‐cell populations we observed simply reflected a response to chronic CMV infection.…”