Antifungal Prophylaxis in AML Patients Receiving Intensive Induction Chemotherapy: A Prospective Observational Study From the Acute Leukaemia French Association (ALFA) Group

Mauricette Michallet, Mohamad Sobh, Stephane Morisset, Alexandre Deloire, Emmanuel Raffoux, Stephane de Botton, Denis Caillot, Sylvain Chantepie, Stephane Girault, Celine Berthon, Sarah Bertoli, Stephane Lepretre, Thibaut Leguay, Sylvie Castaigne, Jean Pierre Marolleau, Cecile Pautas, Jean Valere Malfuson, Norbert Veyn, Thorsten Braun, Lauris GastaudFelipe Suarez, Aline Schmidt, Remy Gressin, Caroline Bonmati, Karine Celli-Lebras, Mohamed El-Hamri, Patricia Ribaud, Herve Dombret, Xavier Thomas, Anne Bergeron

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    Abstract

    Background: Although recommended in patients with acute myeloblastic leukaemia (AML) after induction chemotherapy, real-life use of antifungal prophylaxis (AFP) is different among centres. Materials and Methods: This is an ancillary study to a randomized trial on intensive induction chemotherapy in AML patients (ALFA-0702/NCT00932412), where AFP with posaconazole was recommended. IFIs were graded by investigators and by central reviewers according to the revised EORTC definitions. Experts conclusions were compared to the investigators’ ones. Results: A total of 677 patients were included. Four AFP strategies were reported: Group-1: no AFP (n = 203, 30%), Group-2: posaconazole (n = 241, 36%), Group-3: posaconazole with other AFP (n = 142, 21%), Group-4: other AFP (n = 91, 13%). Experts graded more IFI than investigators: proven/probable IFI, 9.0% (n = 61) versus 6.2% (n = 42). The cumulative incidence at day60 of probable/proven IFI was 13.9% (Group-1); 7.9% (Group-2); 5.6% (Group-3); and 6.6% (Group-4). IFI onset was 26 (19-31) days after induction in Groups 2-3, versus 16 (9-25) days in Group 1 and 20 (12-24) days in Group 4 (P<.001). After a median follow-up of 27.5 months (0.4-73.4), the mortality rate was 38.3%, with 5.4% attributed to IFI. In multivariate analysis, IFI occurrence was an independent risk of death (HR5.63, 95%-CI 2.62-12.08, P<.001). EORTC recommendations were applied in only 57% of patients. In patients without IFI, the rate of AML complete remission was higher. Conclusions: In AML patients, AFP delayed the onset of IFI in addition of decreasing their rate. The frequent misidentification of IFI impacts their appropriate management according to recommendations. hematological remission was more frequent in patients without IFI.

    Original languageEnglish
    Pages (from-to)311-318
    Number of pages8
    JournalClinical Lymphoma, Myeloma and Leukemia
    Volume22
    Issue number5
    DOIs
    Publication statusPublished - 1 May 2022

    Keywords

    • Acute myeloid leukemia
    • Antifungal prophylaxis
    • Fungal infection
    • induction chemotherapy
    • recommendations

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