Prognostic Factors for Survival in Invasive Aspergillosis in Adult Oncohematological Patients.
Authors: Nivoix Yasmine , Velten Michel , Letscher-Bru Valérie , Moghaddam Alireza , Fohrer Cécile , Lioure Bruno , Bilger Karin , Natarajan-Amé Shanti , Lutun Philippe , Marcellin Luc , Bergerat Jean-Pierre , Herbrecht Raoul 
Published: October 2019

Abstract
Despite recent progresses in treatment, invasive aspergillosis (IA) is still associated with high treatment failure and elevated death rates. Prognostic factors have not yet been identified in a large population of oncohematological patients (pts) developing IA. We reviewed all cases of possible, probable or definite IA according to the EORTC/MSG criteria occurring in adult oncohematological pts since January 1997. Two hundred and ninety nine pts received at least one dose of anti-aspergillus therapy and were analyzed for prognosis factors. Demographic, clinical, radiological, biological and mycological variables available at time of start of antifungal therapy were analyzed for their effects on 3-month specific survival (pts dying of another cause were censored at time of death) and 3-month overall survival. All variables with a p-value less than 0.2 in univariate analysis were introduced into a multivariate Cox regression model, allowing for interactions. The analysis was stratified by the type of first line therapy to produce a consistent analysis of the other variables. Underlying condition included allogeneic hematopoietic stem cell transplantation (HSCT) (n=41), autologous HSCT (n=24), solid organ transplantation (SOT) (n=10), acute leukemia (n=91), other hematological malignancy (n=67), solid tumor (n=35) or non-malignant disease (n=21). Infection was localized to the lung in 258 pts, to another single organ, mostly sinuses, in 12 pts and was disseminated in 19 cases. Overall and specific survival rates at 3 months were 52.3% (95% CI: 46.5–57.9%) and 59.5% (95% CI: 53.6–65.0%) respectively. Prognostic factors for 3-month overall survival are shown in table 1. Prognosis factors for 3-month specific survival were the same, with the following exceptions: monocyte count was no more significant (p=0.57), baseline neutrophil count (< vs. ≥ 500 μ L) and radiological aspects (single vs. multiple vs. diffuse lesions) became significant with p-values at 0.003 and 0.048 respectively. Our study identified several risk factors for death in oncohematological pts with IA. These factors should help to early identify pts who would benefit from more aggressive antifungal therapeutic strategies.
Table 1. Three-month overall survival after stratification on treatment Predictor Reference category Hazard ratio 95% CI p-value Host factor AlloHSCT or SOT Hematological malignancy 1.78 1.12–2.84 0.0391 Other 1.52 0.86–2.68 Progression of underlying disease No 4.54 2.68–7.67 <0.001 Prior non-infectious respiratory disease Absence 1.76 1.18–2.62 0.006 Steroids dose ≥ 0.2 mg/kg <0.2 mg/kg 2.33 1.50–3.63 <0.001 Creatinine clearance 30–59 mL/min ≥ 60 mL/min 1.65 1.06–2.55 <0.001 <30 mL/min 2.51 1.56–4.03 Monocytes >100/μ L ≤ 100/μ L 0.59 0.41–0.85 0.004 Site of infection Disseminated Lung only 3.20 1.72–5.93 0.001 Other single organ NA NA Pleural effusion Absence 1.77 1.19–2.63 0.005 Possible IA Probable or definite 0.51 0.34–0.780.002