Cytokine Profile of Patients with Invasive Apsergillosis- Preliminary Results.

Abstract 1500

Invasive Aspergillosis (IA) is an important cause of morbidity and mortality in haemato-oncology patients undergoing haematopoietic stem cell transplantation (HSCT) or chemotherapy resulting in prolonged cytopenia. The host cytokine response to fungal infection in this immunocompromised state is a crucial component of susceptibility and response to IA. The aim of this study was to assess if a unique cytokine profile exist for patients who developed IA compared to those who didn't.

All adult haemato-oncology patients enrolled on the Aspergillosis study, a prospective cohort study of adult haemato-oncology patients undergoing HSCT or chemotherapy, have baseline and fortnightly follow up serum samples profiled for 30 inflammatory cytokines using multiplex bead immunoassays by Luminex 100™ instrument. The cytokines measured were: EGF, Eotaxin, FGF, G-CSF, GM-CSF, HGF, IFN-α, IFN-γ, IL-1RA, IL-1β, IL-2, IL-2R, IL-4, IL5, IL6, IL7, IL-8, IL-10, IL-12p40/p70, IL-13, IL-15, IL-17, IP-10 (CXCL10), MCP-1, MIG, MIP-1α, MIP-1β, Rantes, TNF-α and VEGF.

The first hundred patients enrolled with sufficient follow up data were included in this initial analysis. The median (range) age was 52.5 (19-73) years and M/F ratio was 58/42. The main diagnosis were AML/MDS (40), Myeloma (23), NHL (17) and aplastic anaemia (9) treated by allogeneic HSCT (43), autologous HSCT (32), chemotherapy (20), and immunosuppressive therapy (5). The diagnosis of invasive fungal infection was based on the revised 2008 EORTC/MSG criteria. The incidence of proven and probable infection was 17% and possible infection accounted for 12%. Eight patients were excluded from analysis because of lack of proper baseline sample prior to starting chemotherapy/transplant or had infective episodes that proved to be due to IA. Using a longitudinal logistic regression model (R²= 0.4355, p<0.001) and using each patient as a cluster from baseline to follow-up periods and adjusting for age, sex, underlying diagnosis and treatment received, the following were found to be statistically significantly different between those with proven/probable IA compared to those patients with no evidence of IA: lower IL-10 (P= 0.042), lower IL-12 (P=0.017), higher IL-6 (P=0.001), lower IL-15 (P= 0.026), and higher CXCL-10 (P=0.046). Age correlated significantly with IA (P= 0.014) but not gender (P=0.693).

This preliminary data suggests that there is a significant difference in the cytokine profile between patients with proven/probable IA compared to those with no evidence of fungal infection. Further analysis will be performed on the rest of the cohort to confirm this.