Originally published as JCO Early Release 10.1200/JCO.2008.21.0856 on July 13 2009

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Index to Predict Invasive Mold Infection in High-Risk Neutropenic Patients Based on the Area Over the Neutrophil Curve

From the University Hospital, Hematology Service, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Brazil.

Corresponding author: Marcio Nucci, MD, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255, Cidade Universitária, 21941-913, Rio de Janeiro, Brazil; e-mail: mnucci{at}hucff.ufrj.br.

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.

Supported by Pró Vita, Rio de Janeiro (M.G.), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, Grant No. 300235/93-3 (M.N.)

Presented in part at the 9th International Symposium on Febrile Neutropenia, January 25-27, 2007, Valencia, Spain, and at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 17-20, 2007, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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