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Low Rate of Invasive Fungal Infections During Induction and Consolidation Chemotherapy for Adults with De Novo Acute Myeloid Leukemia Without Anti-mold Prophylaxis: Single-Center 2002–2018 Empirical/Pre-emptive Approach

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Abstract

Broad-spectrum antifungal prophylaxis is currently considered the standard of care for adults with de novo AML for the prevention of invasive fungal infections (IFIs), especially invasive pulmonary aspergillosis (IPA). Because fluconazole has been used in our center as anti-yeast prophylaxis, we sought to analyze in detail the incidence of IFIs over a 17-year period, as well as their impact on outcome. A standardized protocol of patient management, including serum galactomannan screening and thoracic CT-guided diagnostic-driven antifungal therapy, was used in all patients. A total of 214 consecutive adults with de novo AML who were treated in 3 CETLAM (Grupo Cooperativo para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias) protocols from 2002 to 2018 were included. The 90-day incidence of any IFI (including possible cases) was 11% (95% CI 4–15%), most cases occurred during induction chemotherapy (8%, 95% CI 4–12%), and most cases were probable/proven IPA (8%, 95% CI 3–13%). Developing an IFI during induction and consolidation had no impact on 1-year survival. A case–control study with 23 cases of IPA and 69 controls identified induction/re-induction chemotherapy, chronic pulmonary disease and age > 60 years/poor baseline performance status as potential pretreatment risk factors. The current study proves that inpatient induction and consolidation chemotherapy for de novo AML can be given in areas with “a priori” high-burden of airborne molds with fluconazole prophylaxis, while the selective use of anti-mold prophylaxis in patients at very high risk may further reduce the incidence of IFI in this specific clinical scenario.

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Acknowledgements

This study was performed in the setting of the CETLAM cooperative group (Grupo Cooperativo para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias, protocols CETLAM-99, CETLAM-2003 and CETLAM-2012), in part with grants C03/010 and 603/008 from the Instituto de Salud Carlos III, and two grants from Fundació d’Investigació Sant Pau and Fundació “La Caixa” (Barcelona, Spain).

Funding

This study was performed in the setting of the CETLAM cooperative group (Grupo Cooperativo para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias, protocols CETLAM-99, CETLAM-2003 and CETLAM-2012), in part with grants C03/010 and 603/008 from the Instituto de Salud Carlos III, and two grants from Fundació d’Investigació Sant Pau and Fundació “La Caixa” (Barcelona, Spain).

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RM was involved in conception and execution of the research reported in the paper, the integrity and analysis of the data, inpatient care and writing the various versions of the manuscript. In addition, he also had the task of data management and statistical analyses. AG and MS collaborated in patient care, performed most data management, contributed to the conception and execution of the research reported in the paper, and participated in writing or interpreting relevant parts of the manuscript. All other co-authors contributed to the conception and execution of the research reported in the paper, collaborated in patient care and participated in writing or interpreting relevant parts of the manuscript.

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Correspondence to Rodrigo Martino.

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Due to the retrospective nature of the study, ethical approval was waived by our center’s Ethical Committee. However, all patients signed an informed consent for each of the 3 CETLAM protocols in which they were included, which complied with national ethical regulations as well as the principles laid in the 1964 Declaration of Helsinki.

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Martino, R., Garrido, A., Santaliestra, M. et al. Low Rate of Invasive Fungal Infections During Induction and Consolidation Chemotherapy for Adults with De Novo Acute Myeloid Leukemia Without Anti-mold Prophylaxis: Single-Center 2002–2018 Empirical/Pre-emptive Approach. Mycopathologia 185, 639–652 (2020). https://doi.org/10.1007/s11046-020-00461-w

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