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Incidence and outcome of invasive fungal disease after front-line intensive chemotherapy in patients with acute myeloid leukemia: impact of antifungal prophylaxis

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Abstract

Few reports analyze the incidence and clinical outcome of invasive fungal disease (IFD) in patients with newly diagnosed acute myeloid leukemia (AML) undergoing intensive chemotherapy, and thus the impact of different antifungal prophylactic regimens remains unclear. We analyze the incidence and clinical outcome of IFD in a large series of adult AML patients undergoing front-line intensive induction and consolidation chemotherapy between 2004 and 2015 in a single institution. Three antifungal prophylaxis regimens were given (2004–2005 oral fluconazole, 2006–2012 intravenous itraconazole, and 2013–2015 voriconazole). Overall, 285 patients and 589 intensive chemotherapy episodes were assessed (47%) (induction courses 47% and consolidation 53%). The median age was 51 years (range, 17–65). We observed 56 (10%) episodes of IFD. According to the EORTC 2008 criteria, IFD was classified as possible (29, 52%), probable (17, 30%), and proven (10, 18%). Possible/probable/proven IFD rate was significantly lower during HiDAC consolidation as compared to any anthracycline-containing chemotherapy courses (2% vs. 11%, P = 0.001), and under voriconazole prophylaxis as compared to itraconazole and fluconazole (6% vs. 11% vs. 15%, P = 0.007), and the multivariate analysis showed that they were independent risk factors. Patients under voriconazole prophylaxis had shorter hospitalization duration and less frequent use of empirical or directed antifungal therapy. In conclusion, IFD was a frequent complication during upfront intensive chemotherapy courses for adult AML patients. This retrospective study shows that voriconazole prophylaxis was feasible and associated with a lower risk of IFD compared with intravenous itraconazole or oral fluconazole schedules.

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Authorship

Pau Montesinos, Rebeca Rodríguez-Veiga, and Antonio Torres conceived the study, analyzed, and interpreted the data; Pau Montesinos, Rebeca Rodríguez-Veiga, Blanca Boluda, and Antonio Torres wrote the paper; Pau Montesinos, Ignacio Lorenzo, and Rebeca Rodríguez-Veiga performed the statistical analyses; Ignacio Lorenzo, David Martínez-Cuadrón, Miguel Salavert, Javier Pemán, Pilar Calvillo, Isabel Cano, Evelyn Acuña, Ana Villalba, José Luis Piñana, Jaime Sanz, Pilar Solves, Leonor Senent, Ana Vicente, Amparo Sempere, José Cervera, Eva Barragán, Isidro Jarque, Miguel A. Sanz, and Guillermo F. Sanz reviewed the manuscript and contributed to the final draft.

Funding

This study was in part supported by Asociación Medicina e Investigación (A.M.I.), a grant 2012/023 from the Instituto de Investigación Sanitaria La Fe. This paper was supported by an independent medical grant provided by Pfizer, Inc.

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Author notes

  1. Rebeca Rodríguez-Veiga and Pau Montesinos contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell 106, CP: 46026, Valencia, Spain

    Rebeca Rodríguez-Veiga, Pau Montesinos, Blanca Boluda, Ignacio Lorenzo, David Martínez-Cuadrón, Isabel Cano, Evelyn Acuña, Ana Villalba, José Luis Piñana, Jaime Sanz, Pilar Solves, Leonor Senent, Ana Vicente, Amparo Sempere, José Cervera, Eva Barragán, Isidro Jarque, Antonio Torres, Miguel A. Sanz & Guillermo F. Sanz

  2. CIBERONC, Instituto Carlos III, Madrid, Spain

    Pau Montesinos, David Martínez-Cuadrón, Jaime Sanz, Pilar Solves, José Cervera, Isidro Jarque, Miguel A. Sanz & Guillermo F. Sanz

  3. Department of Infectious Diseases, Hospital Universitari i Politècnic La Fe, València, Spain

    Miguel Salavert

  4. Department of Microbiology, Hospital Universitari i Politècnic La Fe, València, Spain

    Javier Pemán

  5. Department of Radiology, Hospital Universitari i Politècnic La Fe, València, Spain

    Pilar Calvillo

  6. Asociación Medicina e Investigación (A.M.I.), Córdoba, Spain

    Antonio Torres

  7. Department of Medicine, Universitat de València, València, Spain

    Miguel A. Sanz & Guillermo F. Sanz

Authors
  1. Rebeca Rodríguez-Veiga
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  2. Pau Montesinos
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  3. Blanca Boluda
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  4. Ignacio Lorenzo
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  5. David Martínez-Cuadrón
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  6. Miguel Salavert
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  7. Javier Pemán
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  8. Pilar Calvillo
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  9. Isabel Cano
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  10. Evelyn Acuña
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  11. Ana Villalba
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  12. José Luis Piñana
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  13. Jaime Sanz
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  14. Pilar Solves
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  15. Leonor Senent
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  16. Ana Vicente
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  17. Amparo Sempere
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  18. José Cervera
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  19. Eva Barragán
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  20. Isidro Jarque
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  21. Antonio Torres
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  22. Miguel A. Sanz
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  23. Guillermo F. Sanz
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Corresponding author

Correspondence to Pau Montesinos.

Ethics declarations

This retrospective study was approved by the Research Ethics Board of the institution according to the Declaration of Helsinki (study number 2013/0036).

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The authors declare that they have no conflict of interest.

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Rodríguez-Veiga, R., Montesinos, P., Boluda, B. et al. Incidence and outcome of invasive fungal disease after front-line intensive chemotherapy in patients with acute myeloid leukemia: impact of antifungal prophylaxis. Ann Hematol 98, 2081–2088 (2019). https://doi.org/10.1007/s00277-019-03744-5

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  • DOI: https://doi.org/10.1007/s00277-019-03744-5

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