Skip to main content

Advanced Search

Haematologica
  • Home
  • Current Issue
  • Ahead Of Print
  • Archive
  • Submit a Manuscript
    • Author Guidelines
    • Reviewer Guidelines
    • Submit a Manuscript
    • Track a Manuscript
  • About Us
    • About Haematologica
    • Editorial Board
    • Our Policies
  • More
    • Advertising
    • Rights & Permissions
    • Alerts
    • Feedback
    • Contact
Voriconazole as secondary antifungal prophylaxis in stem cell transplant recipients
Catherine Cordonnier, Montserrat Rovira, Johan Maertens, Oliver A Cornely, Per Ljungman, Hermann Einsele
Haematologica February 2011 96: e9-e10; doi:10.3324/haematol.2010.038463
Catherine Cordonnier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: carlcord@club-internet.fr
Montserrat Rovira
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Johan Maertens
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver A Cornely
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Per Ljungman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hermann Einsele
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site

Author Affiliations

  1. Catherine Cordonnier1⇓,
  2. Montserrat Rovira2,
  3. Johan Maertens3,
  4. Oliver A Cornely4,
  5. Per Ljungman5 and
  6. Hermann Einsele6
  7. on behalf of the Voriconazole for Secondary Prophylaxis of Invasive Fungal Infections in Patients With Allogeneic Stem Cell Transplants (VOSIFI) study group and the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
  1. 1 Service d’Hematologie Clinique, Hôpital Henri Mondor, AP-HP and Université Paris 12, Créteil, France
  2. 2 Hospital Clinic, Barcelona, Spain
  3. 3 Katholieke Universiteit Leuven and Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium
  4. 4 1st Department of Internal Medicine, CIO Köln Bonn and ZKS Köln (BMBF 01KN0706), CECAD University of Cologne, Cologne, Germany
  5. 5 Karolinska Institute University Hospital, Stockholm, Sweden
  6. 6 Universitätsklinik Würzburg, Würzburg, Germany
  1. Correspondence: Catherine Cordonnier, Service d’Hématologie Clinique, Hôpital Henri Mondor, 51, Av. Maréchal de Lattre de Tassigny, 94000 Créteil, France. Tel.: + 33 1 49 81 20 57; Fax : +33 1 49 81 20 67; E-mail: carlcord{at}club-internet.fr
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

A recently published editorial by Dr. Girmenia addressed the difficult issue of preventing invasive fungal disease in hematology patients. 1 The author concluded that several questions remained unanswered concerning the use of secondary antifungal prophylaxis in this setting. We agree with Dr. Girmenia that most previous reports on secondary antifungal prophylaxis were retrospective, uncontrolled, and potentially biased toward reporting positive experiences, 2 which reduces our ability to come to clear-cut conclusions. An exception is our recently published prospective, non-comparative study of secondary antifungal prophylaxis with voriconazole in allogeneic hematopoietic stem cell transplant recipients. 3

The relapse rate of previous invasive fungal disease during subsequent high-risk periods (i.e. following hematopoietic stem cell transplant or during prolonged neutropenia in general) appears to be extremely high. 2, 4, 5 The use of secondary antifungal prophylaxis in affected hematology patients may, therefore, be of considerable benefit, despite the shortage of prospective data supporting such a strategy. This is actually reflected in current international, European and Italian consensus guidelines which generally grade secondary antifungal prophylaxis for hematopoietic stem cell transplant recipients as “AII” (i.e. highly recommended, limited clinical evidence) or “AIII” (i.e. highly recommended, expert opinion). 6– 8 Ultimately, a placebo-controlled trial would be required to confirm the efficacy of secondary antifungal prophylaxis in hematopoietic stem cell transplant recipients. However, such a study is improbable, given the likely reluctance of clinicians to withhold secondary antifungal prophylaxis from hematopoietic stem cell transplant candidates with a history of invasive fungal disease. The optimal antifungal agents in this setting, on the other hand, remain to be established. Of note, the causative pathogen of the prior invasive fungal disease and the individual response to specific antifungal therapy are major considerations when choosing the optimal agent for secondary antifungal prophylaxis.

A key issue for retrospective clinical trials is the actual definition of secondary antifungal prophylaxis. Dr. Girmenia mentions that the efficacy of secondary anti-fungal prophylaxis in patients with active invasive fungal disease or persistent radiological abnormalities has not yet been clarified. Strictly speaking, however, the term secondary prophylaxis is only applicable to a population with inactive or “apparently resolved” disease, as defined by Sipsas et al. 2 Retrospective studies of secondary anti-fungal prophylaxis were limited by the fact that they generally included patients with presumably inactive as well as those with active invasive fungal disease. Our study of secondary antifungal prophylaxis with voriconazole 2 avoided this issue by enrolling only patients with inactive/resolved invasive fungal disease, according to a list of minimum criteria in agreement with the proposed definitions by Sipsas et al. Our criteria may not have fully ensured a complete cure of the previous episode, but they did allow us to better distinguish between: a) the actual treatment phase of the previous episode; and b) the secondary antifungal prophylaxis phase aiming to avoid disease relapse. While the methodology for evaluating primary antifungal prophylaxis was developed years ago during the fluconazole era, our study represents the first attempt at prospectively assessing secondary antifungal prophylaxis. Although our methodology is certainly open to criticism, it should prove useful for future clinical trials of secondary antifungal prophylaxis in hematology patients.

Another key consideration is the aim of secondary anti-fungal prophylaxis. While primarily aiming to prevent the recurrence of a previous infection, an invasive fungal disease posttransplant may also be due to an entirely new infection. These two types can be difficult to differentiate; for example, if diagnosis of a previous probable aspergillosis was based on a positive galactomannan test, without species identification. Most invasive fungal disease risk factors during acute leukemia induction chemotherapy, including genetic predisposition, likely remain posttransplant. 9 Such patients are consequently at a considerably increased risk of a new invasive fungal disease, even though the previous invasive fungal disease may not relapse. Indeed, candidates for secondary anti-fungal prophylaxis are excellent subjects for illustrating the benefit of antifungal prophylaxis due to their high risk of developing a new or reactivated invasive fungal disease episode. In our study, the one-year cumulative incidence of invasive fungal disease was 6.7%±3.6% among 42 allogeneic hematopoietic stem cell transplant recipients. 2 This is close to the incidence observed with primary prophylaxis 10 and, therefore, strongly supports recent international guidelines recommending voriconazole prophylaxis in allogeneic hematopoietic stem cell transplant recipients with a previous history of invasive aspergillosis. 7 Since the invasive fungal disease incidence during secondary antifungal prophylaxis with voriconazole appears to be so low, it will be extremely difficult to conduct comparative trials in this setting. To detect potential differences between drugs, such trials would have to include hundreds of patients, which may be logistically impossible given the very low incidence of previous invasive fungal disease among hematopoietic stem cell transplant recipients observed in previous case series. 4, 5 Hopefully, the increased use of effective primary prophylaxis will further reduce the number of patients referred to transplant with a past history of invasive fungal disease. For those patients who do fall into this category, secondary antifungal prophylaxis with voriconazole is likely to reduce the incidence of invasive fungal disease and transplant-related mortality.

Acknowledgments

Editorial support was provided by D. Wolf of PAREXEL and was funded by Pfizer Inc.

Footnotes

  • The information provided by the authors about contributions from persons listed as authors and in acknowledgments is available with the full text of this paper at www.haematologica.org.

  • Financial and other disclosures provided by the authors using the ICMJE (www.icmje.org) Uniform Format for Disclosure of Competing Interests are also available at www.haematologica.org.

  • Copyright© Ferrata Storti Foundation

References

  1. 1.↵
    1. Girmenia C
    (2010) Prophylaxis of invasive fungal diseases in patients with hematologic disorders. Haematologica 95(10):1630–2.
    OpenUrlFREE Full Text
  2. 2.↵
    1. Sipsas NV,
    2. Kontoyiannis DP
    (2006) Clinical issues regarding relapsing aspergillosis and the efficacy of secondary antifungal prophylaxis in patients with hematological malignancies. Clin Infect Dis 42(11):1584–91.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Cordonnier C,
    2. Rovira M,
    3. Maertens J,
    4. Olavarria E,
    5. Faucher C,
    6. Bilger K,
    7. et al.
    (2010) Voriconazole for secondary prophylaxis of invasive fungal infection in allogeneic stem cell transplant recipients: results of the VOSIFI Study. Haematologica 95(10):1762–8.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Fukuda T,
    2. Boeckh M,
    3. Guthrie K,
    4. Mattson DK,
    5. Owens S,
    6. Wald A,
    7. et al.
    (2004) Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10 year experience at a single transplant center. Biol Bone Marrow Transplant 10(7):494–503.
    OpenUrl
  5. 5.↵
    1. Martino R,
    2. Parody R,
    3. Fukuda T,
    4. Maertens J,
    5. Theunissen K,
    6. Ho A,
    7. et al.
    (2006) Impact of the intensity of the pretransplant conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic stem cell transplantation: A retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood 108(9):2928–36.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Maertens J,
    2. Marchetti O,
    3. Herbrecht R,
    4. Cornely OA,
    5. Flückiger U,
    6. Frere P,
    7. et al.
    (Jul 26, 2010) European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL3 2009 update. Bone Marrow Transplant, [Epub ahead of print].
  7. 7.↵
    1. Tomblyn M,
    2. Chiller T,
    3. Einsele H,
    4. Gres R,
    5. Spekowitz K,
    6. Soterk J,
    7. et al.
    (2009) Guidelines for preventing infectious complications among hematopoietic stem cell transplant recipients: a global perspective. Biol Blood Marrow Transplant 15(10):1143–238.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Girmenia C,
    2. Barosi G,
    3. Aversa F,
    4. Bacigalupo A,
    5. Barbui T,
    6. Baronciani D,
    7. et al.
    (2009) Prophylaxis and treatment of invasive fungal diseases in allogeneic stem cell transplantation: results of a consensus process by Gruppo Italiano Trapianto di Midollo Osseo (GITMO) Clin Infect Dis 49(8):1226–36.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Bochud PY,
    2. Chein JW,
    3. Marr KA,
    4. Leisenring WM,
    5. Upton A,
    6. Janer M,
    7. et al.
    (2008) Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med 359(17):1766–77.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    1. Wingard JR,
    2. Carter SL,
    3. Walsh TJ,
    4. Kurtzberg J,
    5. Small TN,
    6. Baden LR,
    7. et al.
    (2010) Randomized double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection (IFI) after allogeneic hematopoietic cell transplantation (HCT) Blood 116(24):5111–8.
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top

Vol 96 Issue 2

Haematologica: 96 (2)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
Email

Thank you for your interest in spreading the word about Haematologica.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Voriconazole as secondary antifungal prophylaxis in stem cell transplant recipients
(Your Name) has forwarded a page to you from Haematologica
(Your Name) thought you would like to see this page from the Haematologica web site.
Print
Citation Tools
Voriconazole as secondary antifungal prophylaxis in stem cell transplant recipients
Catherine Cordonnier, Montserrat Rovira, Johan Maertens, Oliver A Cornely, Per Ljungman, Hermann Einsele
Haematologica Feb 2011, 96 (2) e9-e10; DOI: 10.3324/haematol.2010.038463

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Catherine Cordonnier, Montserrat Rovira, Johan Maertens, Oliver A Cornely, Per Ljungman, Hermann Einsele
Haematologica Feb 2011, 96 (2) e9-e10; DOI: 10.3324/haematol.2010.038463
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Request Permissions
  • Tweet Widget
  • Facebook Like
  • Alert me when this article is cited
  • Alert me if a correction is posted

Jump To

  • Article
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

More in this TOC Section

  • Molecular remissions are observed in chronic adult T-cell leukemia/lymphoma in patients treated with mogamulizumab
  • The non-erythroid myeloblast count rule in myelodysplastic syndromes: fruitful or futile?
  • Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses
Show more Online Only Articles

Related Articles

Cited By...

What about you?
Tell us your interests and get all the new contents of Haematologica in advance

 

 

Navigate

  • Home
  • Current issue
  • Ahead of print
  • Archive
  • Info for
    • Authors
    • Reviewers
    • Advertisers
    • Subscribers
  • About us
    • About Haematologica
    • Editorial Board
    • Our policies

For Authors

  • Author guidelines
  • Submit Manuscript
  • Track Manuscript

For Reviewers

  • Reviewer Guidelines
  • Access Your Profile
  • Access Your Tasks
  • 2014 reviewers

For Advertisers

  • Information For Advertising

Education

  • Review Articles
  • Guideline Articles

More

  • Rights & Permissions
  • Advertising
  • Alerts
  • Feedback
  • Contact
  • App

Copyright © 2019 by the Ferrata Storti Foundation

ISSN 0390-6078 print

ISSN 1592-8721 online