Early changes in serum IL-6 and VEGF levels predict clinical outcome following first-line therapy in aggressive non-Hodgkin’s lymphoma

Abstract

Inflammatory cytokines play important roles in the pathogenesis of lymphomas and may reflect underlying biological processes including tumour-host interactions with prognostic information that is not afforded by conventional clinical parameters. Several lines of evidence suggest that serum levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) are independent indicators of long-term outcome in non-Hodgkin's lymphoma (NHL), but the clinical impact of early serial monitoring of these cytokines has not been reported. Serum samples from 64 newly diagnosed patients with aggressive NHL were obtained before the first cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and then weekly until the second cycle was given. Serum IL-6 and VEGF were measured by commercial enzyme-linked immunosorbent assays (ELISA). Pre-treatment serum IL-6 and VEGF levels were significantly correlated to response rate and overall survival. A significant decrease of IL-6 and VEGF levels was observed in the first weeks after CHOP therapy in patients achieving a complete remission after treatment. Multivariate analysis indicated that early changes of IL-6 and VEGF serum levels within the first 3 weeks after initiation of chemotherapy were independent predictors of clinical response even when corrected for the influence of clinical prognostic factors. Only changes in serum IL-6 level had borderline significance for the prediction of overall survival. The data indicate that serial measurements of serum IL-6 and VEGF may be early prognostic indicators and support the hypothesis of a clinical impact by early recognition of poor-risk patients and candidates for new treatment options.

Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy

“…Serum VEGF levels are at best an imperfect marker for VEGF levels within the lymphoma itself but are readily obtained; in a study of 64 patients with aggressive non-Hodgkin's lymphoma (61% DLBCL), early response over the first 3 weeks of treatment correlated with drops in serum VEGF (and IL-6). 25 Although no data exist on the effect of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) on VEGF or its receptors in DLBCL, evidence for downregulation of VEGF mRNA expression by these agents exists in several other model systems. [26][27][28][29][30][31] A model of the potential impact of anthracycline (doxorubicin) administration is presented in Figure 5c.…”

Angiogenesis in nodal B cell lymphomas: a high throughput study

“…Statistical analysis, including descriptive methods, was performed using the SPSS software V. 10.0 for Windows. The Pearson x 2 test and the Spearman rank correlation coefficient were applied where appropriate to demonstrate correlations.…”

The importance of angiogenesis markers in the outcome of patients with diffuse large B cell lymphoma: a retrospective study of 97 patients

“…Several studies have recently suggested an important role in hematologic malignancies as well (Smolej et al 2005;Ribas et al 2004;Pedersen et al 2005;Singhal et al 1999;Dmoszynska et al 2005). There is evidence that angiogenesis, as measured by an increase in angiogenic factors and an increase in microvessel density (MVD), may be important in lymphomagenesis.…”