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Microbial Issues

ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients

Abstract

As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); β-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.

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Acknowledgements

The ECIL Organization Committee is indebted to the companies that supported the expert meetings through educational grants since ECIL 1 in 2005: Astellas Pharma, Bristol-Myers Squibb, Cephalon, Gilead Sciences, Glaxo-Smith Kline Beecham, MSD, Novartis, Pfizer, Schering-Plough, Wyeth, Zeneus-Pharma and Cephalon. We are thankful to Jean-Michel Gosset and the staff of KOBE, Group GL events, Lyon, France for the organization of the meetings. We are also indebted to the participants of the ECIL 3 meeting: Murat Akova, Turkey; Maiken Arendrup, Denmark; Jacques Bille, Switzerland; Catherine Cordonnier, France; Oliver A Cornely, Germany; Eric Dannaoui, France; Rafael De La Camara, Spain; Emma Dellow (Gilead Sciences), UK; Lubos Drgona, Slovakia; Hermann Einsele, Germany; Dan Engelhard, Israel; Ursula Flückiger, Switzerland; Bertrand Gachot, France; Jesus Gonzales-Moreno (MSD), Spain; Andreas Groll, Germany; Ina Hanel (Astellas), Germany; Raoul Herbrecht, France; Claus-Peter Heussel, Germany; Christopher Kibbler, UK; Nikolai Klimko, Russia Michal Kouba, Czech Republic; Fanny Lanternier, France; Alexey Maschan, Russia; Livio Pagano, Italy; Goergios Petrikos, Greece; Zdenek Racil, Czech Republic; Pierre Reusser, Switzerland; Patricia Ribaud, France; Valérie Rizzi-Puechal (Pfizer), France; Markus Ruhnke, Germany; Janos Sinko, Hungary; Anna Skiada, Greece; Jan Styczynski, Poland; Anne Thiebaut, France; Janice Wahl (Schering-Plough) USA; Katherine Ward, UK.

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Correspondence to S Bretagne.

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Competing interests

Oscar Marchetti received unrestricted research grants and/or educational grants and/or speaker's honoraria and/or consultant's honoraria from the Foundation for the Advancement in Medical Microbiology and Infectious Diseases, FAMMID, Lausanne, Switzerland, Associates of Cape Code, BioMérieux—Cepheid, Bio-Rad, Wako, and Roche Diagnostics. Stéphane Bretagne received consultant's honoraria from Myconostica. The remaining authors declare no conflict of interest.

Appendix

Appendix

ECIL Laboratory Working Groups

The ECIL is a common initiative of the following groups or organizations: the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT-IDWP), the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer (EORTC-IDG), the European Leukemia Net (ELN) (EU Grant Number: LSHC-CT-2004) and the International Immunocompromised Host Society (ICHS).

Galactomannan: Paul Verweij (leader), Lena Klingspor, Thomas Lehrnbecher, Johan Maertens.

β-glucan: Oscar Marchetti (leader), Frédéric Lamoth, Mario Cruciani, Elio Castagnola, Olivier Lortholary, Malcolm Richardson.

Cryptococcus antigen and mannan antigen/anti-mannan antibodies: Claudio Viscoli (leader), Malgorzata Mikulska, Maurizio Sanguinetti, Daniel Poulain, Thierry Calandra.

PCR for the diagnosis of invasive aspergillosis: Stéphane Bretagne (leader), Rosemary Barnes, Manuel Cuenca-Estrella, Peter Donnelly, Brian Jones, Lena Klingspor, Thomas Lehrnbecher, Juergen Loeffler, Johan Maertens, Paul Verweij, Philipe Lewis White.

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Marchetti, O., Lamoth, F., Mikulska, M. et al. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant 47, 846–854 (2012). https://doi.org/10.1038/bmt.2011.178

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Keywords

  • galactomannan
  • β-glucan
  • Cryptococcus Ag
  • mannan
  • anti-mannan
  • Aspergillus PCR
  • invasive fungal diseases

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