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Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

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Abstract

Invasive fungal infections cause substantial morbidity and mortality in immunocompromised patients, particularly in those with haematological malignancies and recipients of allogeneic haematopoietic stem cell transplantation. Difficulties in diagnosing invasive fungal infections and subsequent delays in treatment initiation lead to unfavourable outcomes and emphasise the importance of prophylaxis. Since the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology in 2009, results of 14 additional clinical studies have been published comprising 2,899 patients and initiating this update. Key recommendations for adult patients are as follows: Posaconazole remains the drug of choice during remission-induction chemotherapy in acute myeloid leukaemia, myelodysplastic syndrome and allogeneic haematopoietic stem cell transplantation with graft versus host disease (AI). In the pre-engraftment period of allogeneic transplantation, several antifungals are appropriate and can be recommended with equal strength: voriconazole (BI), micafungin (BI), fluconazole (BI) and posaconazole (BII). There is poor evidence regarding antifungal prophylaxis in the post-engraftment period of allogeneic haematopoietic stem cell transplantation if no steroids for treatment of graft versus host disease are required. Aerosolised liposomal amphotericin B inhalation in conjunction with fluconazole can be used in patients with prolonged neutropenia (BII).

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Conflict of interest

Dr. Tacke reports personal fees from MSD, personal fees from Gilead Sciences GmbH, peronal fees from Pfizer and personal fees from Astellas, outside the submitted work. Dr. Tacke is affiliated to the COMBACTE consortium. She has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115523; resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution.

Dr. Buchheidt reports grants and personal fees from Gilead Sciences, grants and personal fees from Pfizer, personal fees and non-financial support from Astellas, personal fees and non-financial support from Merck Sharp & Dohme/Merck, outside the submitted work.

Dr. Karthaus reports personal fees from MSD, personal fees from Astellas and personal fees from Pfizer, outside the submitted work.

Dr. Krause reports personal fees from MSD and personal fees from Gilead, outside the submitted work.

Dr. Maschmeyer reports personal fees from Gilead, personal fees from Pfizer and personal fees from MSD, outside the submitted work.

Dr. Neumann reports personal fees from Gilead and personal fees from MDS, outside the submitted work.

Dr. Ostermann reports grants and personal fees from MSD, grants and personal fees from Gilead and personal fees from Astellas, outside the submitted work.

Dr. Penack reports personal fees from MSD, personal fees from Astellas, personal fees from Gilead and grants from Pfizer, outside the submitted work.

Dr. Rieger has nothing to disclose.

Dr. Ruhnke reports grants from commercial sponsor (Pfizer, Roche Molecular Diagnostics) and personal fees from commercial sponsor (Astellas, Gilead, Pfizer), outside the submitted work.

Dr. Sandherr has nothing to disclose.

Dr. Schweer has nothing to disclose.

Dr. Ullmann reports grants and personal fees from MSD, personal fees from Gilead, personal fees from Pfizer and personal fees from Astellas, outside the submitted work.

Dr. Cornely is supported by the German Federal Ministry of Research and Education (BMBF grant 01KN1106); received research grants from 3 M, Actelion, Astellas, Basilea, Bayer, Celgene, Cubist, F2G, Genzyme, Gilead, GSK, Merck/MSD, Miltenyi, Optimer, Pfizer, Quintiles and Viropharma; a consultant to 3 M, Astellas, Basilea, Cubist, F2G, Gilead, GSK, Merck/MSD, Optimer, Pfizer, Sanofi Pasteur and Summit/Vifor; and received lecture honoraria from Astellas, Gilead, Merck/MSD and Pfizer.

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Authors and Affiliations

  1. Klinik I für Innere Medizin, Uniklinik Köln, Köln, Germany

    Daniela Tacke, Katharina E. Schweer & Oliver A. Cornely

  2. III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany

    Dieter Buchheidt

  3. Klinik für Hämatologie und Onkologie, Klinikum Neuperlach, München, Germany

    Meinolf Karthaus

  4. Hämatologie und Internistische Onkologie, Universitätsklinikum Erlangen, Erlangen, Germany

    Stefan W. Krause

  5. Klinik für Hämatologie, Onkologie und Palliativmedizin, Ernst von Bergmann Klinikum, Potsdam, Germany

    Georg Maschmeyer

  6. Ambulantes Onkologiezentrum, Wolfsburg, Germany

    Silke Neumann

  7. Medizinische Klinik und Poliklinik III, Klinikum der Universität München, München, Germany

    Helmut Ostermann & Christina Rieger

  8. Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, Charité-Universitätsmedizin Berlin Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Olaf Penack

  9. Medizinische Klinik und Poliklinik mit Schwerpunkt Onkologie und Hämatologie, Charité-Universitätsmedizin Berlin, Campus Mitte Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Markus Ruhnke

  10. Schwerpunktpraxis für Hämatologie und Onkologie, Weilheim, Germany

    Michael Sandherr

  11. Medizinische Klinik und Poliklinik II-Schwerpunkt Infektiologie, Universitätsklinikum Würzburg, Würzburg, Germany

    Andrew J. Ullmann

  12. Zentrum für Klinische Studien (BMBF 01KN1106), Medical Fuculty, University of Cologne, Cologne, Germany

    Oliver A. Cornely

  13. CECAD – Cologne Excellence Cluster on Cellular Stress Responses in Aging–Associated Diseases, Medical Faculty, University of Cologne, Cologne, Germany

    Oliver A. Cornely

  14. Center for Integrated Oncology CIO Köln-Bonn, Medical Faculty, University of Cologne, Cologne, Germany

    Daniela Tacke, Katharina E. Schweer & Oliver A. Cornely

  15. German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany

    Oliver A. Cornely

  16. CHIR-Net, Chirurgisches Regionalzentrum Witten/Herdecke—Köln, Universität Witten/Herdecke gGmbH/Universität Köln, Cologne, Germany

    Oliver A. Cornely

  17. COMBACTE-consortium https://www.combacte.com/

    Daniela Tacke & Katharina E. Schweer

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  1. Daniela Tacke
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  2. Dieter Buchheidt
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  9. Christina Rieger
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  13. Andrew J. Ullmann
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  14. Oliver A. Cornely
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Correspondence to Oliver A. Cornely.

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Author contributions

Systematic literature search was conducted by Daniela Tacke and Oliver A. Cornely. Data were extracted and tabulated by Daniela Tacke, Katharina E. Schweer and Oliver A. Cornely, and preliminary recommendations by patient group were proposed for discussion and sent to the members of the committee on Antifungal Prophylaxis of the Infectious Diseases Working Party of the German Society for Haematology and Oncology (AGIHO), i.e. the authors, Olaf Penack, Michael Sandherr, Markus Ruhnke, Stefan W. Krause, Christina Rieger, Andrew J. Ullmann, Silke Neumann, Meinolf Karthaus, Dieter Buchheidt, Werner J. Heinz, Georg Maschmeyer and Helmut Ostermann. Tables were revised following email-based discussion and then presented for final discussion with the committee at the AGIHO guideline conference in Frankfurt on November 13, 2013. The draft manuscript, including the results of the AGIHO guideline conference, was prepared by Daniela Tacke and Oliver A. Cornely and sent to authors for critical revision. All authors approved the submitted version.

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Tacke, D., Buchheidt, D., Karthaus, M. et al. Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Ann Hematol 93, 1449–1456 (2014). https://doi.org/10.1007/s00277-014-2108-y

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