The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent

Michael Ozga; Ying Huang; James S. Blachly; Nicole R. Grieselhuber; Sarah Wall; Karilyn Larkin; Tamanna Haque; Alison R. Walker; Bhavana Bhatnagar; Gregory Behbehani; Sumithira Vasu; Joseph E. Maakaron; Mark Lustberg; Alice S. Mims

doi:10.1016/j.clml.2020.08.013

The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent

Michael Ozga, Ying Huang, James S. Blachly, Nicole R. Grieselhuber, Sarah Wall, Karilyn Larkin, Tamanna Haque, Alison R. Walker, Bhavana Bhatnagar, Gregory Behbehani, Sumithira Vasu, Joseph E. Maakaron, Mark Lustberg, Alice S. Mims

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Background: Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting. Patients and Methods: We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI. The Fisher exact test compared patients with cIFI versus without, and a multivariable logistic regression model estimated odds for cIFI. Results: Sixty-seven (57%) patients had cIFI, with 48 possible IFIs, 17 probable, and 2 proven cases. There was no difference in incidence based on home zip code, but the presence of chronic obstructive pulmonary disease was highly associated with cIFI (P = .001), as was male gender (P = .01). Neutropenia at treatment initiation was borderline in significance (P = .08). In diagnostics, 9% of patients had positive serum fungal markers, and 30 patients underwent bronchoscopy, with only 27% of cases yielding positive results. There was a difference in treatment regimens between patients receiving antifungal prophylaxis with mold coverage versus without mold coverage with respect to cIFI (P = .04). Conclusions: cIFI in patients with AML treated with HMAs remains significant, especially in males and those with chronic obstructive pulmonary disease, who were found to be at higher risk. This may prompt clinicians to consider anti-mold prophylaxis in this setting.

Original language	English (US)
Pages (from-to)	e76-e83
Journal	Clinical Lymphoma, Myeloma and Leukemia
Volume	21
Issue number	1
DOIs	https://doi.org/10.1016/j.clml.2020.08.013
State	Published - Jan 1 2021

Bibliographical note

Funding Information:
JS Blachly reports a consulting/advisory role for AstraZeneca and Kite Pharma; travel/accommodations/expense from Oxford Nanopore Technologies; patents: a sequencing technology patent pending; and honoraria from LifeSci Venture Partners. AR Walker reports travel/accommodations/expense from Gilead Sciences; and research funding from Gilead Sciences. AS Mims reports a consulting/advisory role for Astellas Pharma, Agios, PTC Therapeutics, Jazz Pharmaceuticals, Abbvie/Genentech, Syndax Pharmaceuticals, and Kura Oncology, Inc. The remaining authors have stated that they have no conflicts of interest.Research reported in this publication was supported by the Division of Hematology and Infectious Disease at The Ohio State University and James Comprehensive Cancer Center, with all authors listed above as assisting in the critical appraisal of its scientific work and writing of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Funding Information:
Research reported in this publication was supported by the Division of Hematology and Infectious Disease at The Ohio State University and James Comprehensive Cancer Center , with all authors listed above as assisting in the critical appraisal of its scientific work and writing of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Funding Information:
JS Blachly reports a consulting/advisory role for AstraZeneca and Kite Pharma; travel/accommodations/expense from Oxford Nanopore Technologies; patents: a sequencing technology patent pending; and honoraria from LifeSci Venture Partners. AR Walker reports travel/accommodations/expense from Gilead Sciences; and research funding from Gilead Science s. AS Mims reports a consulting/advisory role for Astellas Pharma, Agios, PTC Therapeutics, Jazz Pharmaceuticals, Abbvie/Genentech, Syndax Pharmaceuticals, and Kura Oncology, Inc. The remaining authors have stated that they have no conflicts of interest.

Publisher Copyright:
© 2020 The Authors

Keywords

Acute myeloid leukemia
Anti-mold azoles
Antifungal prophylaxis
Decitabine
Risk stratification

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.clml.2020.08.013

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Ozga, M., Huang, Y., Blachly, J. S., Grieselhuber, N. R., Wall, S., Larkin, K., Haque, T., Walker, A. R., Bhatnagar, B., Behbehani, G., Vasu, S., Maakaron, J. E., Lustberg, M., & Mims, A. S. (2021). The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent. Clinical Lymphoma, Myeloma and Leukemia, 21(1), e76-e83. https://doi.org/10.1016/j.clml.2020.08.013

Ozga, M, Huang, Y, Blachly, JS, Grieselhuber, NR, Wall, S, Larkin, K, Haque, T, Walker, AR, Bhatnagar, B, Behbehani, G, Vasu, S, Maakaron, JE, Lustberg, M & Mims, AS 2021, 'The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent', Clinical Lymphoma, Myeloma and Leukemia, vol. 21, no. 1, pp. e76-e83. https://doi.org/10.1016/j.clml.2020.08.013

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title = "The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent",

abstract = "Background: Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting. Patients and Methods: We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI. The Fisher exact test compared patients with cIFI versus without, and a multivariable logistic regression model estimated odds for cIFI. Results: Sixty-seven (57%) patients had cIFI, with 48 possible IFIs, 17 probable, and 2 proven cases. There was no difference in incidence based on home zip code, but the presence of chronic obstructive pulmonary disease was highly associated with cIFI (P = .001), as was male gender (P = .01). Neutropenia at treatment initiation was borderline in significance (P = .08). In diagnostics, 9% of patients had positive serum fungal markers, and 30 patients underwent bronchoscopy, with only 27% of cases yielding positive results. There was a difference in treatment regimens between patients receiving antifungal prophylaxis with mold coverage versus without mold coverage with respect to cIFI (P = .04). Conclusions: cIFI in patients with AML treated with HMAs remains significant, especially in males and those with chronic obstructive pulmonary disease, who were found to be at higher risk. This may prompt clinicians to consider anti-mold prophylaxis in this setting.",

keywords = "Acute myeloid leukemia, Anti-mold azoles, Antifungal prophylaxis, Decitabine, Risk stratification",

author = "Michael Ozga and Ying Huang and Blachly, {James S.} and Grieselhuber, {Nicole R.} and Sarah Wall and Karilyn Larkin and Tamanna Haque and Walker, {Alison R.} and Bhavana Bhatnagar and Gregory Behbehani and Sumithira Vasu and Maakaron, {Joseph E.} and Mark Lustberg and Mims, {Alice S.}",

note = "Funding Information: JS Blachly reports a consulting/advisory role for AstraZeneca and Kite Pharma; travel/accommodations/expense from Oxford Nanopore Technologies; patents: a sequencing technology patent pending; and honoraria from LifeSci Venture Partners. AR Walker reports travel/accommodations/expense from Gilead Sciences; and research funding from Gilead Sciences. AS Mims reports a consulting/advisory role for Astellas Pharma, Agios, PTC Therapeutics, Jazz Pharmaceuticals, Abbvie/Genentech, Syndax Pharmaceuticals, and Kura Oncology, Inc. The remaining authors have stated that they have no conflicts of interest.Research reported in this publication was supported by the Division of Hematology and Infectious Disease at The Ohio State University and James Comprehensive Cancer Center, with all authors listed above as assisting in the critical appraisal of its scientific work and writing of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Funding Information: Research reported in this publication was supported by the Division of Hematology and Infectious Disease at The Ohio State University and James Comprehensive Cancer Center , with all authors listed above as assisting in the critical appraisal of its scientific work and writing of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Funding Information: JS Blachly reports a consulting/advisory role for AstraZeneca and Kite Pharma; travel/accommodations/expense from Oxford Nanopore Technologies; patents: a sequencing technology patent pending; and honoraria from LifeSci Venture Partners. AR Walker reports travel/accommodations/expense from Gilead Sciences; and research funding from Gilead Science s. AS Mims reports a consulting/advisory role for Astellas Pharma, Agios, PTC Therapeutics, Jazz Pharmaceuticals, Abbvie/Genentech, Syndax Pharmaceuticals, and Kura Oncology, Inc. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

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doi = "10.1016/j.clml.2020.08.013",

language = "English (US)",

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T1 - The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent

AU - Ozga, Michael

AU - Huang, Ying

AU - Blachly, James S.

AU - Grieselhuber, Nicole R.

AU - Wall, Sarah

AU - Larkin, Karilyn

AU - Haque, Tamanna

AU - Walker, Alison R.

AU - Bhatnagar, Bhavana

AU - Behbehani, Gregory

AU - Vasu, Sumithira

AU - Maakaron, Joseph E.

AU - Lustberg, Mark

AU - Mims, Alice S.

N1 - Funding Information: JS Blachly reports a consulting/advisory role for AstraZeneca and Kite Pharma; travel/accommodations/expense from Oxford Nanopore Technologies; patents: a sequencing technology patent pending; and honoraria from LifeSci Venture Partners. AR Walker reports travel/accommodations/expense from Gilead Sciences; and research funding from Gilead Sciences. AS Mims reports a consulting/advisory role for Astellas Pharma, Agios, PTC Therapeutics, Jazz Pharmaceuticals, Abbvie/Genentech, Syndax Pharmaceuticals, and Kura Oncology, Inc. The remaining authors have stated that they have no conflicts of interest.Research reported in this publication was supported by the Division of Hematology and Infectious Disease at The Ohio State University and James Comprehensive Cancer Center, with all authors listed above as assisting in the critical appraisal of its scientific work and writing of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Funding Information: Research reported in this publication was supported by the Division of Hematology and Infectious Disease at The Ohio State University and James Comprehensive Cancer Center , with all authors listed above as assisting in the critical appraisal of its scientific work and writing of this manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Funding Information: JS Blachly reports a consulting/advisory role for AstraZeneca and Kite Pharma; travel/accommodations/expense from Oxford Nanopore Technologies; patents: a sequencing technology patent pending; and honoraria from LifeSci Venture Partners. AR Walker reports travel/accommodations/expense from Gilead Sciences; and research funding from Gilead Science s. AS Mims reports a consulting/advisory role for Astellas Pharma, Agios, PTC Therapeutics, Jazz Pharmaceuticals, Abbvie/Genentech, Syndax Pharmaceuticals, and Kura Oncology, Inc. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2020 The Authors

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Background: Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting. Patients and Methods: We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI. The Fisher exact test compared patients with cIFI versus without, and a multivariable logistic regression model estimated odds for cIFI. Results: Sixty-seven (57%) patients had cIFI, with 48 possible IFIs, 17 probable, and 2 proven cases. There was no difference in incidence based on home zip code, but the presence of chronic obstructive pulmonary disease was highly associated with cIFI (P = .001), as was male gender (P = .01). Neutropenia at treatment initiation was borderline in significance (P = .08). In diagnostics, 9% of patients had positive serum fungal markers, and 30 patients underwent bronchoscopy, with only 27% of cases yielding positive results. There was a difference in treatment regimens between patients receiving antifungal prophylaxis with mold coverage versus without mold coverage with respect to cIFI (P = .04). Conclusions: cIFI in patients with AML treated with HMAs remains significant, especially in males and those with chronic obstructive pulmonary disease, who were found to be at higher risk. This may prompt clinicians to consider anti-mold prophylaxis in this setting.

AB - Background: Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting. Patients and Methods: We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI. The Fisher exact test compared patients with cIFI versus without, and a multivariable logistic regression model estimated odds for cIFI. Results: Sixty-seven (57%) patients had cIFI, with 48 possible IFIs, 17 probable, and 2 proven cases. There was no difference in incidence based on home zip code, but the presence of chronic obstructive pulmonary disease was highly associated with cIFI (P = .001), as was male gender (P = .01). Neutropenia at treatment initiation was borderline in significance (P = .08). In diagnostics, 9% of patients had positive serum fungal markers, and 30 patients underwent bronchoscopy, with only 27% of cases yielding positive results. There was a difference in treatment regimens between patients receiving antifungal prophylaxis with mold coverage versus without mold coverage with respect to cIFI (P = .04). Conclusions: cIFI in patients with AML treated with HMAs remains significant, especially in males and those with chronic obstructive pulmonary disease, who were found to be at higher risk. This may prompt clinicians to consider anti-mold prophylaxis in this setting.

KW - Acute myeloid leukemia

KW - Anti-mold azoles

KW - Antifungal prophylaxis

KW - Decitabine

KW - Risk stratification

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The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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