#25: Survival and Risk Factors Associated with Mortality due to Invasive Aspergillosis in Pediatric Oncology Patients in Mexico City

Abstract

Abstract Background Invasive Aspergillosis (IA) has been reported as the most frequent life-threatening opportunist mold infectious disease in immunocompromised subjects, mainly in oncology patients Its incidence has been increasing over the years, with a reported mortality from 35% to 70%. Risk factor for IA mortality has been poorly described in middle-income settings. We aimed to identify risk factors associated with IA mortality and to report the survival in a middle-income setting. Methods Case–control study at Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City from January 2004 to April 2017. We identified patients <18 years old with cancer and diagnosis of proven or probable IA, according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Neutropenia, chemotherapy, use of steroids, hematopoietic stem cell transplantation (HSCT), graft vs. host disease (GVHD) and disseminated disease (defined as the affection of 2 or more sites) were compared between surviving and deceased patients with IA. Fisher exact test or Student’s t-test were performed to identify independent risk factors for IA-related mortality, and a binary logistic regression model was used. Kaplan–Meier analysis was performed to calculate survival rates at days 30 and 90 after IA diagnosis. Results Seventy-four IA events in 72 patients were identified. The mean age was 8.4 years, 63% were male. 89% of IA presented in hematologic malignances, being ALL the most frequent diagnosis in 54% of cases; 8.1% (6) were in HSCT patients (5 allogeneic HSCT). Of the 74 IA, 42% and 58% were classified as proven and probable AI respectively. Localized disease (76%) was more frequent than disseminated. Lungs were the most frequent sites of primary infection (84%) but an unusual site of infections, such as heart, pericardium, pulmonary artery, bowel, skin, and spleen, were reported by histopathology. Aspergillus flavus was the most frequent species isolated (42%) followed by A. fumigatus (27%). Voriconazol was first line of therapy in 95% of cases, while combined therapy was used during the course of infections in 53% of cases. The disseminated disease was an independent risk factor associated with IA mortality (OR 4.2 95% CI, 1.5 – 15.2, P = 0.007). Overall mortality was 64%; however, directed IA-related mortality was 35%. On day 30 and day 90 after IA diagnosis, overall survival was 66% and 32%, respectively. Two IA were diagnosed post mortem. IA-related mortality was 67% in HSCT (P = 0.009). All HSCT patients which death was associated with IA presented GVHD. Conclusions In our population, IA-related mortality (35%) was similar to that reported globally, nevertheless IA-related mortality in HSCT was high (67%). Disseminated disease and neutropenia were identified as risk factors for mortality due to IA. Efforts should be made to early identification of IA and prompt start of antifungal treatment, to reduce the incidence and consequences of disseminated disease.