title: Epidemiology of invasive fungal infections during induction therapy in adults with acute lymphoblastic leukemia: a GRAALL-2005 study.
abstract: Little data have been published concerning invasive fungal infections during treatment of acute lymphoblastic leukemia (ALL). Patients included between May 2006 and October 2012 in the multicenter phase III trial for newly diagnosed ALL (GRAALL-2005) were retrospectively reviewed for the occurrence of IFI using the EORTC modified criteria. These patients did not routinely receive antifungal prophylaxis. Among 969 patients included (median age 47 years), 65 (6.7%) developed IFI during induction chemotherapy: 26 (3.3%) invasive aspergillosis (IA), 33 (3.4%) invasive candidiasis (IC) and six other IFI. For IA, the median time between induction therapy and IA diagnosis was 20 days. Diagnosis was probable in 22 cases and proven in four. Aspergillus antigen in serum was tested in all cases and positive in 24. Overall 12-week mortality after diagnosis of IA was 5/26 and attributable mortality related to the infection was 4/26 (15.4%). For IC, the median time between induction therapy and diagnosis was 19 days. Diagnosis was proven in 29 episodes. Candida albicans was the major pathogen in yeast infections (16/27). Overall 12-week mortality after diagnosis of IC was 8/33 (24.2%) and attributable mortality related to the infection was 7/33. The median delay between induction chemotherapy initiation and attributable death related to IC was 15 days. These findings may help to optimize the future management of ALL patients, and as in AML advocate systematic monitoring and the development of prophylactic or preemptive antifungal treatments.
authors.affiliation: a Department of Hematology and UMR 5525 CNRS-UJF , University Hospital , Grenoble , France.
authors.forename: Clara
authors.initials: C
authors.lastname: Mariette
authors.affiliation: b Department of Hematology Saint-Etienne , University Hospital , Saint-Etienne , France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Tavernier
authors.affiliation: c Infection Control Department , University Hospital , Besançon , France.
authors.forename: Didier
authors.initials: D
authors.lastname: Hocquet
authors.affiliation: d Department of Hematology , University Hospital , Toulouse , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Huynh
authors.affiliation: e Department of Hematology , University Hospital , Saint-Antoine , France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Isnard
authors.affiliation: f Department of Hematology , University Hospital , Nice , France.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Legrand
authors.affiliation: g Department of Hematology Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) , Coordination Office , Pierre Bénite , France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lhéritier
authors.affiliation: h Department of Hematology , University Paris Diderot, Institut Universitaire d'Hématologie (IUH), University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris (AP-HP) , Paris , France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.affiliation: h Department of Hematology , University Paris Diderot, Institut Universitaire d'Hématologie (IUH), University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris (AP-HP) , Paris , France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: i Department of Hematology and Inserm U 892/CNRS 6299 , University Hospital , Angers , France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.affiliation: a Department of Hematology and UMR 5525 CNRS-UJF , University Hospital , Grenoble , France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: a Department of Hematology and UMR 5525 CNRS-UJF , University Hospital , Grenoble , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Thiébaut
mesh_terms: D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology; D058365:Candidiasis, Invasive / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects*; D000072742:Invasive Fungal Infections / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000935:Antifungal Agents
keywords: Acute lymphoblastic leukemia; invasive aspergillosis; invasive candidiasis; invasive fungal infections