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Research Papers:

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

Claire Calmettes, Frederic Gabriel, Elodie Blanchard, Vincent Servant, Stéphane Bouchet, Nathanael Kabore, Edouard Forcade, Camille Leroyer, Audrey Bidet, Valérie Latrabe, Thibaut Leguay, Stephane Vigouroux, Reza Tabrizi, Dominique Breilh, Isabelle Accoceberry, Manuel Tunon de Lara, Arnaud Pigneux, Noel Milpied and Pierre-Yves Dumas _

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Oncotarget. 2018; 9:26724-26736. https://doi.org/10.18632/oncotarget.25477

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Abstract

Claire Calmettes1, Frederic Gabriel2, Elodie Blanchard3, Vincent Servant4, Stéphane Bouchet5, Nathanael Kabore6, Edouard Forcade1, Camille Leroyer7, Audrey Bidet8, Valérie Latrabe9, Thibaut Leguay1, Stephane Vigouroux1, Reza Tabrizi1, Dominique Breilh4, Isabelle Accoceberry2, Manuel Tunon de Lara3, Arnaud Pigneux1, Noel Milpied1 and Pierre-Yves Dumas1

1Department of Hematology and Cell Therapy, University Hospital, F-33000 Bordeaux, France

2Laboratory of Mycology, University Hospital, F-33000 Bordeaux, France

3Department of Respiratory Diseases, University Hospital, F-33000 Bordeaux, France

4Pharmacy, University Hospital, F-33000 Bordeaux, France

5Department of Clinical Pharmacology, University Hospital, F-33000 Bordeaux, France

6Medical Information Department, University Hospital, F-33000 Bordeaux, France

7Department of Infection Control, University Hospital, F-33000 Bordeaux, France

8Laboratory of Hematology, University Hospital, F-33000 Bordeaux, France

9Thoracic and Cardiovascular Imaging Department, University Hospital, F-33000 Bordeaux, France

Correspondence to:

Pierre-Yves Dumas, email: [email protected]

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

Received: February 28, 2018     Accepted: May 07, 2018     Published: June 01, 2018

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.


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