1158. D-index as a Novel Index to Predict Invasive Fungal Disease in High-Risk Neutropenic Pediatric Cancer Patients and Hematopoietic Stem Cell Transplantation

Abstract

BackgroundProlonged and profound neutropenia are risk factors for invasive fungal disease (IFD) during febrile neutropenia (FN) episodes. The D-index combines both depth and duration of neutropenia in a single assessment and has been proposed as a useful tool to exclude or predict IFD in high-risk adult patients. We assessed the D-index as a predictor of IFD in pediatric cancer patients.MethodsWe conducted a retrospective study of pediatric oncology patients with FN at UCM Comer Children’s Hospitals. IFD was stratified as possible, probable, and proven according EORTC/MSG criteria. Patients considered high risk of IFD were receiving intensive chemotherapy with expected prolonged neutropenia >7 days, including, but not limited to, AML, high-risk acute ALL, and hematopoietic stem cell transplantation (HSCT). The D1-index was equal to 2t1 + 3t2, where t1, and t2 are the number of days from the first day of neutropenia < 500mm3 and < 100/ mm3 respectively, until the development of IFD. The D2-index approximates the area over the neutrophil curve during neutropenia. A cumulative D-index (c-D-index) was also calculated using the first day of neutropenia until the date of the first clinical manifestation of IFD. We compared duration of neutropenia vs D-index vs c-D-index as a predictor of IFD using receiver operating characteristic curve (ROC)/AUC analysis.Figure 1 Figure 2 ResultsWe identified 455 FN episodes in 203 high-risk patients. 53/455 (11.6%) had IFD, 12 (2.6%) proven, 23 (5%) probable, and 18 (4%) possible. The median of D1, D2 indexes and c-D-index were significantly higher in patients developing IFD (38, 5225, 7352) compared to the non-IFD group (26, 3857, 5169) (P=.001, P=.001, and P=.01) respectively. The ROC curve of D-index and c-D-index (figure 1,2,3) showed better performance (AUC of 0.85,0.89, 0.81) respectively compared to the duration of neutropenia alone. The ROC was highest when D-index was combined with prolonged fever >5 days (AUC 0.94)Figure 3 Figure 4 ConclusionThe D-index may be a useful tool to stratify high-risk pediatric patients according to risk of IFD. The c-D-index, particularly, may be a useful tool to guide for empiric antifungal therapy and diagnostic testing. Prospective multi-center studies using these tools are required to refine the clinical approach to IFD.Disclosures All Authors: No reported disclosures