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 , Stephane Bouchet 5 , Nathanael Kabore 6 , Edouard Forcade 1 , Camille Leroyer 7 , Audrey Bidet 8 , Valerie 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 and Pierre-Yves Dumas 1 1 Department of Hematology and Cell Therapy, University Hospital, F-33000 Bordeaux, France 2 Laboratory of Mycology, University Hospital, F-33000 Bordeaux, France 3 Department of Respiratory Diseases, University Hospital, F-33000 Bordeaux, France 4 Pharmacy, University Hospital, F-33000 Bordeaux, France 5 Department of Clinical Pharmacology, University Hospital, F-33000 Bordeaux, France 6 Medical Information Department, University Hospital, F-33000 Bordeaux, France 7 Department of Infection Control, University Hospital, F-33000 Bordeaux, France 8 Laboratory of Hematology, University Hospital, F-33000 Bordeaux, France 9 Thoracic and Cardiovascular Imaging Department, University Hospital, F-33000 Bordeaux, France Correspondence to: Pierre-Yves Dumas, email: pierre-yves.dumas@u-bordeaux.fr 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.