Skip to main content

Advertisement

Log in

Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Invasive fungal infections (IFI) remain a leading cause of morbidity and mortality in immunocompromised patients. This retrospective single-center study analyzed incidence, treatment and outcome of invasive fungal infections in 1,095 patients with hematological malignancies receiving either cytoreductive chemotherapy or autologous or allogeneic hematopoietic stem cell transplantation at our institution between 1995 and 2004. IFI occurred in 167/1,095 (15%) patients with a significant increase over time (12.7% between 1995 and 2000 vs. 18.1% in the later IFI cohort, P = 0.0134). Fifty-four (32%) patients had proven, 70 (42%) patients had probable, and 43 (26%) patients suffered from possible IFI according to EORTC/MSG criteria. In 108/124 (87%) cases with proven or probable IFI, moulds were the causative pathogens. Both, Aspergillus fumigatus (n = 46) and Aspergillus terreus (n = 41) were predominant. Yeast infections (Candida spp.) were documented in 16/124 (10%) cases with proven or probable IFI. Median overall survival of the entire IFI cohort was 7 (3–17) months. Overall survival was significantly better in patients with probable or possible IFI (37 and 38%, respectively) compared with patients with proven IFI (28%, P = 0.019). In 35% of patients, IFI was the principal cause of death with a significant decrease over time (44% in time cohort 1995–2000 vs. 28% in the later IFI cohort, P = 0.018) accompanied by an increased use of novel antifungals. By multivariate analysis, only proven IFI was significantly predictive for death (HR 1.7, P = 0.018). A significant decrease in fungus-related deaths was observed despite a significant increase of IFI over time, probably due to improved diagnostic and therapeutic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14. doi:10.1086/323335.

    Article  CAS  PubMed  Google Scholar 

  2. Pagano L, Caira M, Candoni A, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.

    PubMed  Google Scholar 

  3. Bow EJ. Considerations in the approach to invasive fungal infection in patients with haematological malignancies. Br. J. Haematol. 2008;140:133–52.

    Article  PubMed  Google Scholar 

  4. Barnes PD, Marr KA. Risks, diagnosis and outcomes of invasive fungal infections in haematopoietic stem cell transplant recipients. Br J Haematol. 2007;139:519–31. doi:10.1111/j.1365-2141.2007.06812.x.

    Article  PubMed  Google Scholar 

  5. Cornet M, Fleury L, Maslo C, Bernard JF, Brucker G. Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area. J Hosp Infect. 2002;51:288–96. doi:10.1053/jhin.2002.1258.

    Article  CAS  PubMed  Google Scholar 

  6. Denning DW. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis. 1996;23:608–15.

    Article  CAS  PubMed  Google Scholar 

  7. Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32:358–66. doi:10.1086/318483.

    Article  CAS  PubMed  Google Scholar 

  8. Singh N, Paterson DL. Aspergillus infection in transplant recipients. Clin Microbiol Rev. 2005;18:44–69. doi:10.1128/CMR.18.1.44-69.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bedini A, Venturelli C, Mussini C, et al. Epidemiology of candidaemia and antifungal susceptibility patterns in an Italian tertiary-care hospital. J Clin Microbiol. 2006;12:75–80.

    CAS  Google Scholar 

  10. Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood. 2002;100:4358–66. doi:10.1182/blood-2002-05-1496.

    Article  CAS  PubMed  Google Scholar 

  11. Cordonnier C, Ribaud P, Herbrecht R, et al. Prognostic factors for death due to invasive aspergillosis after hematopoietic stem cell transplantation: a 1-year retrospective study of consecutive patients at French transplantation centers. Clin Infect Dis. 2006;42:955–63. doi:10.1086/500934.

    Article  CAS  PubMed  Google Scholar 

  12. Lass-Flörl C, Resch G, Nachbaur D, et al. The value of computed tomography-guided percutaneous lung biopsies in diagnosing invasive fungal infections in immunocompromised patients. Clin Infect Dis. 2007;45:101. doi:10.1086/521245.

    Article  Google Scholar 

  13. Patterson TF. Advances and challenges in management of invasive mycoses. Lancet. 2005;366:1013–25. doi:10.1016/S0140-6736(05)67381-3.

    Article  PubMed  Google Scholar 

  14. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15. doi:10.1056/NEJMoa020191.

    Article  CAS  PubMed  Google Scholar 

  15. Kauffman CA. Clinical efficacy of new antifungal agents. Curr Opin Microbiol. 2006;9:483–8. doi:10.1016/j.mib.2006.08.001.

    Article  CAS  PubMed  Google Scholar 

  16. Boeckh M, Kim HW, Flowers ME, Meyers JD, Bowden RA. Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation—a randomized double-blind placebo-controlled study. Blood. 2006;107:1800–5. doi:10.1182/blood-2005-09-3624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Marr KA, Seidel K, Slavin MA, et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood. 2000;96:2055–61.

    CAS  PubMed  Google Scholar 

  18. Marr KA, Crippa F, Leisenring W, et al. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood. 2004;103:1527–33. doi:10.1182/blood-2003-08-2644.

    Article  CAS  PubMed  Google Scholar 

  19. Einsele H, Hebart H, Roller G, et al. Detection and identification of fungal pathogens in blood by using molecular probes. J Clin Microbiol. 1997;35:1353–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Maertens J, Theunissen K, Lodewyck T, Lagrou K, Eldere JV. Advances in the serological diagnosis of invasive Aspergillus infections in patients with haematological disorders. Mycoses. 2007;50:2–17. doi:10.1111/j.1439-0507.2007.01375.x.

    Article  CAS  PubMed  Google Scholar 

  21. Lass-Flörl C, Gunsilius E, Gastl G, Freund M, Dierich MP, Petzer A. Clinical evaluation of Aspergillus-PCR for detection of invasive aspergillosis in immunosuppressed patients. Mycoses. 2005;48:12–7. doi:10.1111/j.1439-0507.2005.01104.x.

    Article  PubMed  Google Scholar 

  22. Walsh TJ, Lee J, Dismukes WE. Decisions about voriconazole versus liposomal amphotericin B N Engl J Med. 2002;346:1499. doi:10.1056/NEJM200205093461915.

    Article  PubMed  Google Scholar 

  23. Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347:2020–9. doi:10.1056/NEJMoa021585.

    Article  CAS  PubMed  Google Scholar 

  24. Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39:797–802. doi:10.1086/423380.

    Article  CAS  PubMed  Google Scholar 

  25. Sendid B, Cotteau A, Francois N, et al. Candidaemia and antifungal therapy in French University Hospital: rough trends over a decade and possible links. BMC Infect Dis. 2006;6:80. doi:10.1186/1471-2334-6-80.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Böhme A, Ruhnke M, Buchheidt D, et al. Treatment of fungal infections in hematology and oncology—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol. 2003;82:133–40. doi:10.1007/s00277-003-0767-1.

    Article  Google Scholar 

  27. Post MJ, Lass-Flörl C, Gastl G, Nachbaur D. Invasive fungal infections in allogeneic and autologous stem cell transplant recipients: a single-center study of 166 transplanted patients. Transpl Infect Dis. 2007;9:189–95. doi:10.1111/j.1399-3062.2007.00219.x.

    Article  CAS  PubMed  Google Scholar 

  28. Cornillet A, Camus C, Nimubona S, et al. Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and non neutropenic patients: a 6-year survey. Clin Infect Dis. 2006;43:577–84. doi:10.1086/505870.

    Article  CAS  PubMed  Google Scholar 

  29. Denning DW, Marinus A, Cohen J, et al. An EORTC multicentre prospective survey of invasive aspergillosis in haematological patients: diagnosis and therapeutic outcome. EORTC Invasive Fungal Infections Cooperative Group. J Infect. 1998;37:173–80. doi:10.1016/S0163-4453(98)80173-4.

    Article  CAS  PubMed  Google Scholar 

  30. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis. 2007;44:531–40. doi:10.1086/510592.

    Article  PubMed  Google Scholar 

  31. Martino R, Subira M, Rovira M, et al. Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients. Br J Haematol. 2002;116:475–82. doi:10.1046/j.1365-2141.2002.03259.x.

    Article  PubMed  Google Scholar 

  32. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell recipients. Clin Infect Dis. 2002;34:909–17. doi:10.1086/339202.

    Article  PubMed  Google Scholar 

  33. Cailliod D, Casasnovas O, Bernard A, et al. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol. 1997;15:139–47.

    Article  Google Scholar 

  34. Metcalf SC, Dockrell DH. Improved outcomes associated with advances in therapy for invasive fungal infections in immunocompromised hosts. J Infect. 2007;55:287–99. doi:10.1016/j.jinf.2007.06.012.

    Article  CAS  PubMed  Google Scholar 

  35. Spanakis EK, Aperis G, Mylonakis G. New agents for the treatment of fungal infections: clinical efficacy and gaps in coverage. Clin Infect Dis. 2006;43:1060–8. doi:10.1086/507891.

    Article  CAS  PubMed  Google Scholar 

  36. Hachem RY, Kontoyiannis DP, Boktour MR, et al. Aspergillus terreus: an emerging amphotericin B-resistant opportunistic mold in patients with hematologic malignancies. Cancer. 2004;101:194–600. doi:10.1002/cncr.20554.

    Article  Google Scholar 

  37. Lass-Flörl C, Fille M, Gunsilius E, Gastl G, Nachbaur D. Disseminated infection with Prototheca zopfii after unrelated stem cell transplantation for leukemia. J Clin Microbiol. 2004;42:4907–8. doi:10.1128/JCM.42.10.4907-4908.2004.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jutta Auberger.

About this article

Cite this article

Auberger, J., Lass-Flörl, C., Ulmer, H. et al. Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol 88, 508–515 (2008). https://doi.org/10.1007/s12185-008-0184-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-008-0184-2

Keywords

Navigation