Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Sibylle C Mellinghoff^{1

2}, Jens Panse³, Nael Alakel⁴, Gerhard Behre⁵, Dieter Buchheidt⁶, Maximilian Christopeit⁷, Justin Hasenkamp⁸, Michael Kiehl⁹, Michael Koldehoff¹⁰, Stefan W Krause¹¹, Nicola Lehners¹², Marie von Lilienfeld-Toal¹³, Annika Y Löhnert¹⁴, Georg Maschmeyer¹⁵, Daniel Teschner¹⁶, Andrew J Ullmann¹⁷, Olaf Penack¹⁸, Markus Ruhnke¹⁹, Karin Mayer²⁰, Helmut Ostermann²¹, Hans-H Wolf²², Oliver A Cornely^{23

14

24}

Affiliations

¹ Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. sibylle.mellinghoff@uk-koeln.de.
² Department I of Internal Medicine, German Centre for Infection Research (DZIF), University Hospital of Cologne, University of Cologne, Cologne, Germany. sibylle.mellinghoff@uk-koeln.de.
³ Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
⁴ Department I of Internal Medicine, Haematology and Oncology, University Hospital Dresden, Dresden, Germany.
⁵ Division of Haematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
⁶ Department of Internal Medicine-Haematology and Oncology, Mannheim University Hospital, Heidelberg University, Mannheim, Germany.
⁷ Department of Stem Cell Transplantation, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
⁸ Clinic for Haematology and Medical Oncology with Department for Stem Cell Transplantation, University Medicine Göttingen, Göttingen, Germany.
⁹ Department I for Internal Medicine, Klinikum Frankfurt (Oder), Frankfurt (Oder), Germany.
¹⁰ Department of Bone Marrow Transplantation, West German Cancer Centre, University Hospital of Essen, University of Duisburg-Essen, Duisburg, Germany.
¹¹ Department V for Internal Medicine, University Hospital Erlangen, Erlangen, Germany.
¹² Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
¹³ Department of Haematology and Oncology, University Hospital of Jena, Jena, Germany.
¹⁴ Department I of Internal Medicine, German Centre for Infection Research (DZIF), University Hospital of Cologne, University of Cologne, Cologne, Germany.
¹⁵ Department of Haematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany.
¹⁶ Department of Haematology, Medical Oncology, and Pneumology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
¹⁷ Department II of Internal Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
¹⁸ Department for Haematology, Oncology and Tumour immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁹ Department of Haematology and Oncology, Paracelsus-Kliniken Osnabrück, Osnabrück, Germany.
²⁰ Department III of Internal Medicine, University Hospital Bonn, Bonn, Germany.
²¹ Department of Haematology and Oncology, University of Munich, Munich, Germany.
²² Department IV of Internal Medicine, University Hospital Halle, Halle, Germany.
²³ Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
²⁴ Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany.

PMID: 29218389
PMCID: PMC5754425
DOI: 10.1007/s00277-017-3196-2

Review

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Sibylle C Mellinghoff et al. Ann Hematol. 2018 Feb.

. 2018 Feb;97(2):197-207.

doi: 10.1007/s00277-017-3196-2. Epub 2017 Dec 7.

Authors

Affiliations

¹ Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. sibylle.mellinghoff@uk-koeln.de.
² Department I of Internal Medicine, German Centre for Infection Research (DZIF), University Hospital of Cologne, University of Cologne, Cologne, Germany. sibylle.mellinghoff@uk-koeln.de.
³ Department of Oncology, Haematology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
⁴ Department I of Internal Medicine, Haematology and Oncology, University Hospital Dresden, Dresden, Germany.
⁵ Division of Haematology and Oncology, Leipzig University Hospital, Leipzig, Germany.
⁶ Department of Internal Medicine-Haematology and Oncology, Mannheim University Hospital, Heidelberg University, Mannheim, Germany.
⁷ Department of Stem Cell Transplantation, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
⁸ Clinic for Haematology and Medical Oncology with Department for Stem Cell Transplantation, University Medicine Göttingen, Göttingen, Germany.
⁹ Department I for Internal Medicine, Klinikum Frankfurt (Oder), Frankfurt (Oder), Germany.
¹⁰ Department of Bone Marrow Transplantation, West German Cancer Centre, University Hospital of Essen, University of Duisburg-Essen, Duisburg, Germany.
¹¹ Department V for Internal Medicine, University Hospital Erlangen, Erlangen, Germany.
¹² Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
¹³ Department of Haematology and Oncology, University Hospital of Jena, Jena, Germany.
¹⁴ Department I of Internal Medicine, German Centre for Infection Research (DZIF), University Hospital of Cologne, University of Cologne, Cologne, Germany.
¹⁵ Department of Haematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany.
¹⁶ Department of Haematology, Medical Oncology, and Pneumology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
¹⁷ Department II of Internal Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
¹⁸ Department for Haematology, Oncology and Tumour immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁹ Department of Haematology and Oncology, Paracelsus-Kliniken Osnabrück, Osnabrück, Germany.
²⁰ Department III of Internal Medicine, University Hospital Bonn, Bonn, Germany.
²¹ Department of Haematology and Oncology, University of Munich, Munich, Germany.
²² Department IV of Internal Medicine, University Hospital Halle, Halle, Germany.
²³ Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
²⁴ Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany.

PMID: 29218389
PMCID: PMC5754425
DOI: 10.1007/s00277-017-3196-2

Abstract

Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. Since the last edition of antifungal prophylaxis recommendations of the German Society for Haematology and Medical Oncology in 2014, seven clinical trials regarding antifungal prophylaxis in patients with haematological malignancies have been published, comprising 1227 patients. This update assesses the impact of this additional evidence and effective revisions. Our key recommendations are the following: prophylaxis should be performed with posaconazole delayed release tablets during remission induction chemotherapy for AML and MDS (AI). Posaconazole iv can be used when the oral route is contraindicated or not feasible. Intravenous liposomal amphotericin B did not significantly decrease IFI rates in acute lymphoblastic leukaemia (ALL) patients during induction chemotherapy, and there is poor evidence to recommend it for prophylaxis in these patients (CI). Despite substantial risk of IFI, we cannot provide a stronger recommendation for these patients. There is poor evidence regarding voriconazole prophylaxis in patients with neutropenia (CII). Therapeutic drug monitoring TDM should be performed within 2 to 5 days of initiating voriconazole prophylaxis and should be repeated in case of suspicious adverse events or of dose changes of interacting drugs (BIItu). General TDM during posaconazole prophylaxis is not recommended (CIItu), but may be helpful in cases of clinical failure such as breakthrough IFI for verification of compliance or absorption.

Keywords: Amphotericin B; Antifungal prophylaxis; Fluconazole; Invasive fungal infection; Isavuconazole; Itraconazole; Liposomal; Posaconazole.

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Conflict of interest statement

Author JP received honoraria, travel support by MSD Sharp & Dohme, Gilead Sciences, Pfizer, Astellas Pharma. Author DB has received honoraria and research grants by Astellas, Basilea, Gilead Sciences, Merck Sharp & Dohme/Merck (MSD), and Pfizer. Author MC has received fees by Basilea, Gilead, and MSD. Author MKi is a consultant and on the speakers’ bureaus of MSD, and he is a consultant for Gilead and on the speakers’ bureau of Astellas. Author MvLT is supported by the German Federal Ministry of Research and Education (BMBF grants 01EO1002 and 13GW0096D); has received research grants from Pfizer and MSD, is a consultant to Merck/MSD; and received honoraria or travel grants from Basilea, Gilead, Merck/MSD, and Astellas. Author GM has been a consultant to Gilead and F2G and received honoraria for lectures from Gilead, Pfizer, Basilea, and Astellas. Author DT received honoraria and travel grant from Gilead and MSD. Travel grant from Astellas and Jazz. Consultant of advisory board for MSD and Pfizer. Author AJU has received support for travel to meetings from Astellas and Basilea. He is a consultant and on the speakers’ bureaus of Astellas, Gilead, MSD, and Pfizer. He has also received support for travel and accommodation from Astellas, Boehringer Ingelheim, Gilead, MSD, and Pfizer for activities unrelated to the current study. His institution has received grants from Astellas, Gilead, MSD, and Pfizer. Author OP received research grants from Bio-Rad and Gilead; is consultant to Merck/MSD and Gilead; and received lecture honoraria and travel grants from Astellas, Gilead, Pfizer, and Merck/MSD. Author MR is commercially sponsored by Basilea. Author HO received research grants from Gilead and MSD; is consultant to Astellas and MSD; and received lecture honoraria and travel grants from Astellas, Basilea, Gilead, Pfizer, and Merck/MSD. Author OAC is supported by the German Federal Ministry of Research and Education and the European Commission and has received research grants from, is an advisor to, or received lecture honoraria from Achaogen, Actelion, Amplyx, Anacor, Arsanis, Astellas, AstraZeneca, Basilea, Bayer, Cidara, Da Volterra, F2G, Gilead, GSK, Janssen, Matinas, MedPace, Melinta, Menarini, Merck/MSD, Miltenyi, Paratek, Pfizer, Rempex, Roche, Sanofi Pasteur, Scynexis, Seres, Summit, Tetraphase, Medicines Company, and Vical. All remaining authors have declared no conflicts of interest.

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Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Affiliations

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Medical

Research Materials

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