Index to predict invasive mold infection in high-risk neutropenic patients based on the area over the neutrophil curve

Abstract

Purpose: Patients with prolonged and profound neutropenia are at high risk to develop invasive mold infections (IMIs). We developed an index (D-index) that combines duration and severity of neutropenia. The aim of this study was to test the D-index as a predictor of IMI.

Patients and methods: The D-index was based on a graph plotting the absolute neutrophil counts during neutropenia and was the area over the neutrophil curve. We tested the D-index in 11 patients with acute myeloid leukemia (AML) who developed IMI during neutropenia and 33 AML patients without IMI (controls). We also calculated a cumulative D-index (c-D-index), defined as the cumulative D-index from the start of neutropenia until the date of the first clinical manifestation of IMI in patient cases. We compared the D-index and c-D-index with duration of neutropenia and defined a cutoff for IMI using the receiver operating characteristic (ROC) curve.

Results: The median duration of neutropenia and profound neutropenia of patient cases were significantly higher compared with controls (P = .002 and P = .001, respectively), as were the D-index (P < .001) and c-D-index (P = .02). The D-index and c-D-index performed better than duration of neutropenia in ROC curve analysis. For a cutoff point of 5,800 of the c-D-index, the sensitivity and specificity were 91% and 58%, respectively, and for a prevalence of IMI of 5%, 10%, and 15%, the negative predictive values were 99%, 98%, and 97%, respectively.

Conclusion: The high negative predictive value of the c-D-index may be of help in defining different risks for IMI in febrile neutropenic patients.