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. 2018 Jun 1;9(42):26724-26736.
doi: 10.18632/oncotarget.25477.

Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis

Claire Calmettes  1 , Frederic Gabriel  2 , Elodie Blanchard  3 , Vincent Servant  4 , Stéphane Bouchet  5 , Nathanael Kabore  6 , Edouard Forcade  1 , Camille Leroyer  7 , Audrey Bidet  8 , Valérie Latrabe  9 , Thibaut Leguay  1 , Stephane Vigouroux  1 , Reza Tabrizi  1 , Dominique Breilh  4 , Isabelle Accoceberry  2 , Manuel Tunon de Lara  3 , Arnaud Pigneux  1 , Noel Milpied  1 , Pierre-Yves Dumas  1
Affiliations

Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis

Claire Calmettes et al. Oncotarget. .

Abstract

Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment. We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension. Clinical, radiological, microbiological features and treatment response of patients with invasive aspergillosis that occurred despite posaconazole prophylaxis were analyzed. Diagnostic accuracy of serum galactomannan assay according to posaconazole plasma concentrations has been performed. A total of 288 patients with acute myeloid leukemia, treated by induction chemotherapy, who received posaconazole prophylaxis for more than five days were included in the present study. The incidence of invasive aspergillosis was 8% with 12 (4.2%), 8 (2.8%) and 3 (1%), possible, probable and proven invasive aspergillosis, respectively. Posaconazole plasma concentration was available for 258 patients. Median duration of posaconazole treatment was 17 days, and median posaconazole plasma concentration was 0.5 mg/L. None of patients with invasive aspergillosis and posaconazole concentration ≥ 0.5 mg/L had a serum galactomannan positive test. Sensitivity of serum galactomannan assay to detect probable and proven invasive aspergillosis was 81.8%. Decreasing the cut-off value for serum galactomannan optical density index from 0.5 to 0.3 increased sensitivity to 90.9%. In a homogenous cohort of acute myeloid leukemia patients during induction chemotherapy, increasing the posaconazole concentration decreases the sensitivity of serum galactomannan assay.

Keywords: acute myeloid leukemia; galactomannan enzyme immunoassay; invasive aspergillosis; posaconazole; sensitivity.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Receiver operator characteristic curves, using multiple index cutoff values to define positivity
The index cutoff value defining positivity decreases from the highest to lowest value as the curve moves from left to right.
See this image and copyright information in PMC

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