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Ann Hematol. 2018 Feb;97(2):197-207. doi: 10.1007/s00277-017-3196-2. Epub 2017 Dec 7.

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).

Author information

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.

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

PMID:
29218389
PMCID:
PMC5754425
DOI:
10.1007/s00277-017-3196-2
[Indexed for MEDLINE]
Free PMC Article

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