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Review

High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies

by
Giovanni Mori
1,2,
Sara Diotallevi
3,
Francesca Farina
4,
Riccardo Lolatto
3,
Laura Galli
3,
Matteo Chiurlo
1,3,
Andrea Acerbis
1,4,
Elisabetta Xue
4,5,
Daniela Clerici
4,
Sara Mastaglio
4,
Maria Teresa Lupo Stanghellini
4,
Marco Ripa
1,3,
Consuelo Corti
4,
Jacopo Peccatori
4,
Massimo Puoti
6,7,
Massimo Bernardi
4,
Antonella Castagna
1,3,
Fabio Ciceri
1,4,
Raffaella Greco
4 and
Chiara Oltolini
3,6,*
1
Infectious Diseases Unit, Vita-Salute San Raffaele University, 20132 Milan, Italy
2
Infectious Diseases Unit, Ospedale Santa Chiara, 38122 Trento, Italy
3
Infectious Diseases Unit, IRCCS San Raffaele Scientific Institute, 20127 Milan, Italy
4
Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
5
Centre for Immuno-Oncology, National Cancer Institute, Eliminate NIH, Bethesda, MD 20850, USA
6
Infectious Diseases Unit, ASST Grande Ospedale Metropolitano Niguarda, 20161 Milan, Italy
7
Faculty of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy
*
Author to whom correspondence should be addressed.
Microorganisms 2024, 12(1), 117; https://doi.org/10.3390/microorganisms12010117
Submission received: 11 December 2023 / Revised: 30 December 2023 / Accepted: 3 January 2024 / Published: 6 January 2024
(This article belongs to the Special Issue Challenges in the Management of Infectious Complications in Neutropenic Cancer Patients)
Review Reports Versions Notes

Abstract

Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non-Aspergillus invasive mold diseases. Here, we perform a narrative review, discussing the major advances of the last decade on prophylaxis, the diagnosis of and the treatment of IFDs in patients with high-risk neutropenic fever undergoing remission induction chemotherapy for AML/MDS and allo-HSCT. Then, we present our single-center retrospective experience on b-IFDs in 184 AML/MDS patients undergoing high-dose chemotherapy while receiving posaconazole (n = 153 induction treatments, n = 126 consolidation treatments, n = 60 salvage treatments). Six cases of probable/proven b-IFDs were recorded in six patients, with an overall incidence rate of 1.7% (6/339), which is in line with the literature focused on MAP with azoles. The incidence rates (IRs) of b-IFDs (95% confidence interval (95% CI), per 100 person years follow-up (PYFU)) were 5.04 (0.47, 14.45) in induction (n = 2), 3.25 (0.0013, 12.76) in consolidation (n = 1) and 18.38 (3.46, 45.06) in salvage chemotherapy (n = 3). Finally, we highlight the current challenges in the field of b-IFDs; these include the improvement of diagnoses, the expanding treatment landscape of AML with molecular targeted drugs (and related drug–drug interactions with azoles), evolving transplantation techniques (and their related impacts on IFDs’ risk stratification), and new antifungals and their features (rezafungin and olorofim).
Keywords: neutropenic fever; invasive fungal diseases; acute leukaemia; allogeneic hematopoietic stem cell transplantation; antifungal prophylaxis neutropenic fever; invasive fungal diseases; acute leukaemia; allogeneic hematopoietic stem cell transplantation; antifungal prophylaxis

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MDPI and ACS Style

Mori, G.; Diotallevi, S.; Farina, F.; Lolatto, R.; Galli, L.; Chiurlo, M.; Acerbis, A.; Xue, E.; Clerici, D.; Mastaglio, S.; et al. High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies. Microorganisms 2024, 12, 117. https://doi.org/10.3390/microorganisms12010117

AMA Style

Mori G, Diotallevi S, Farina F, Lolatto R, Galli L, Chiurlo M, Acerbis A, Xue E, Clerici D, Mastaglio S, et al. High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies. Microorganisms. 2024; 12(1):117. https://doi.org/10.3390/microorganisms12010117

Chicago/Turabian Style

Mori, Giovanni, Sara Diotallevi, Francesca Farina, Riccardo Lolatto, Laura Galli, Matteo Chiurlo, Andrea Acerbis, Elisabetta Xue, Daniela Clerici, Sara Mastaglio, and et al. 2024. "High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies" Microorganisms 12, no. 1: 117. https://doi.org/10.3390/microorganisms12010117

APA Style

Mori, G., Diotallevi, S., Farina, F., Lolatto, R., Galli, L., Chiurlo, M., Acerbis, A., Xue, E., Clerici, D., Mastaglio, S., Lupo Stanghellini, M. T., Ripa, M., Corti, C., Peccatori, J., Puoti, M., Bernardi, M., Castagna, A., Ciceri, F., Greco, R., & Oltolini, C. (2024). High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies. Microorganisms, 12(1), 117. https://doi.org/10.3390/microorganisms12010117

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