D-index and invasive fungal infections (IFIs) in adult acute myeloid leukemia (AML) patients with the first episode of febrile neutropenia

Thanawat Rattanathammethee, Kawin Munsamai, Teerachat Punnachet, Nonthakorn Hantrakun, Pokpong Piriyakhuntorn, Sasinee Hantrakool, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong, Adisak Tantiworawit, Lalita Norasetthada, Thanawat Rattanathammethee, Kawin Munsamai, Teerachat Punnachet, Nonthakorn Hantrakun, Pokpong Piriyakhuntorn, Sasinee Hantrakool, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong, Adisak Tantiworawit, Lalita Norasetthada

Abstract

Introduction: This study aimed to evaluate the performance of the D-index, a calculated measure of neutropenic burden, in predicting the risk of invasive fungal infections (IFIs) in acute myeloid leukemia (AML) patients.

Methods: A retrospective study of adult AML patients who received the first induction chemotherapy and developed febrile neutropenia was conducted. Clinical characteristics, laboratory data, and the calculation of the D-index and cumulative D-index (c-D-index) were collected and analyzed between patients with and without IFIs.

Results: A total of 101 patients were included, with 16 (15.8%) patients who developed IFIs. Clinical characteristics, antifungal prophylaxis, and AML cytogenetic risk were similar between patients with or without IFIs. The results showed that the D-index and c-D-index were more effective in predicting IFIs than the duration of neutropenia. With the D-index cutoff of 7083, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.3%, 83.5%, 48.2%, and 95.9%, respectively. c-D-index at 5625 revealed sensitivity, specificity, PPV, and NPV for IFIs of 68.8%, 68.2%, 28.9%, and 92.1%, respectively. Using this cutoff of c-D-index, patients without IFIs were overtreated with an antifungal regimen in 45 (52.9%) cases.

Conclusion: The D-index and c-D-index were helpful indicators for defining the risk of IFIs in AML patients with febrile neutropenia.

Conflict of interest statement

The authors have declared that no competing interests exist.

Copyright: © 2023 Rattanathammethee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Figures

Fig 1. Illustrated figure of an example…
Fig 1. Illustrated figure of an example of D-index calculation.
D-index was derived from the difference between the expected neutrophil area (Ae) and the observed area under the curve (Ao). Ae was calculated from the product of 500/μl of ANC and the days of grade 4 neutropenia. Ao was calculated from the sum of the trapezoidal area under the neutrophil curve.
Fig 2. Flow diagram of total recruitment…
Fig 2. Flow diagram of total recruitment alongside inclusion and exclusion criteria.
Fig 3. ROC curve analysis between the…
Fig 3. ROC curve analysis between the D-index, c-D-index, duration of grade 4 neutropenia and profound neutropenia for predicting IFIs.
A: Comparison between D-index and grade 4 neutropenia (AuROC of 0.937 vs. AuROC of 0.628; P <0.001), B: Comparison between D-index and profound neutropenia (AuROC of 0.937 vs. AuROC of 0.744; P <0.001), C: Comparison between c-D-index and grade 4 neutropenia (AuROC of 0.802 vs. AuROC of 0.628; P = 0.012), D: Comparison between c-D-index and profound neutropenia (AuROC of 0.802 vs. AuROC of 0.744; P = 0.295).

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