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Infection

Risk factors for invasive aspergillosis in neutropenic patients with hematologic malignancies

Leukemia volume 19, pages 545–550 (2005)Cite this article

Abstract

Risk factors for invasive aspergillosis (IA) are incompletely identified and may undergo changes due to differences in medical practice. A cohort of 189 consecutive, adult patients with neutropenia hospitalized in the hemato-oncology ward of the University hospital Berne between 1995 and 1999 were included in a retrospective study to assess risk factors for IA. In total, 45 IA cases (nine proven, three probable, 33 possible), 11 patients with refractory fever and 133 controls were analyzed. IA cases had more often acute leukemia or myelodysplastic syndrome (MDS) (88 vs 38%, P<0.001) and a longer duration of neutropenia (mean 20.6 vs 9.9 days, P<0.001). They also had fewer neutropenic episodes during the preceding 6 months (mean 0.42 vs 1.03, P<0.001), that is, confirmed (82%) and probable (73%) IA occurred most often during the induction cycle. A short time interval (⩽14 days) between neutropenic episodes increased the risk of IA four-fold (P=0.06). Bacteremia, however, was not related to the number of preceding neutropenic episodes. Therefore, neutropenic patients with leukemia or MDS have the highest risk of IA. The risk is highest during the first induction cycle of treatment and increases with short-time intervals between treatment cycles.

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References

  1. Bodey G, Bueltmann B, Duguid W, Gibbs D, Hanak H, Hotchi M et al. Fungal infections in cancer patients: an international autopsy survey. Eur J Clin Microbiol Dis 1992; 11: 99–109.

    Article  CAS  Google Scholar 

  2. Denning DW . Invasive aspergillosis. Clin Infect Dis 1998; 26: 781–805.

    Article  CAS  Google Scholar 

  3. Denning DW . Therapeutic outcome in invasive aspergillosis. Clin Infect Dis 1996; 23: 608–615.

    Article  CAS  Google Scholar 

  4. von Eiff M, Roos N, Schulten R, Hesse M, Zuhlsdorf M, van de Loo J . Pulmonary aspergillosis: early diagnosis improves survival. Respiration 1995; 62: 341–347.

    Article  CAS  Google Scholar 

  5. Prentice HG, Kibbler CC, Prentice AG . Towards a targeted, risk-based, antifungal strategy in neutropenic patients. Br J Haematol 2000; 110: 273–284.

    Article  CAS  Google Scholar 

  6. Gerson SL, Talbot GH, Hurwitz S, Strom BL, Lusk EJ, Cassileth PA . Prolonged granulocytopenia: the major risk factor for invasive aspergillosis in patients with acute leukemia. Ann Int Med 1984; 100: 345–351.

    Article  CAS  Google Scholar 

  7. Baddley JW, Stroud TP, Salzmann D, Pappas PG . Invasive mold infections in allogenic bone marrow transplant recipients. Clin Infect Dis 2001; 32: 1319–1324.

    Article  CAS  Google Scholar 

  8. Roilides E, Uhlig K, Venzon D, Pizzo PA, Walsh TJ . Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon. Infect Immun 1993; 61: 4870–4877.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ng TT, Robson GD, Denning DW . Hydrocortisone-enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology 1994; 140: 2475–2479.

    Article  CAS  Google Scholar 

  10. Bow EJ, Loewen R, Cheang MS, Schacter B . Invasive fungal disease in adults undergoing remission-induction therapy for acute myeloid leukemia: the pathogenetic role of the antileukemic regimen. Clin Infect Dis 1995; 21: 316–319.

    Article  Google Scholar 

  11. Coiffier B, Frobert Y, Revol L . Polymorphonuclear function in acute myeloblastic leukemia. Biomedicine 1977; 27: 94–96.

    CAS  PubMed  Google Scholar 

  12. Warnock DW, Hajjeh RA, Lasker BA . Epidemiology and prevention of invasive aspergillosis. Curr Infect Dis Rep 2001; 3: 507–516.

    Article  Google Scholar 

  13. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F 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.

    Article  CAS  Google Scholar 

  14. Charlson ME, Pompei P, Ales KL, MacKenzie CR . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373–383.

    Article  CAS  Google Scholar 

  15. Denning DW, Marinus A, Cohen J, Spence D, Herbrecht R, Pagano L 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: 173–180.

    Article  CAS  Google Scholar 

  16. Lortholary O, Ascioglu S, Moreau P, Herbrecht R, Marinus A, Casassus P et al. Invasive aspergillosis as an opportunistic infection in nonallografted patients with multiple myeloma: a European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the Intergroupe Francais du Myelome. Clin Infect Dis 2000; 30: 41–46.

    Article  CAS  Google Scholar 

  17. Wiley JM, Smith N, Leventhal BG, Graham ML, Strauss LC, Hurwitz CA et al. Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariante analysis of risk factors. J Clin Oncol 1990; 8: 280–286.

    Article  CAS  Google Scholar 

  18. Oren I, Haddad N, Finkelstein R, Rowe JM . Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: before and after chemoprophylaxis and institution of HEPA filters. Am J Hematol 2001; 66: 257–262.

    Article  CAS  Google Scholar 

  19. Pagano L, Girmenia C, Mele L, Ricci P, Tosti ME, Nosari A, et al., GIMEMA Infection Program, Gruppo Italiano Malattie Ematologiche dell’Adulto. Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program. Haematologica 2001; 86: 862–870.

    CAS  PubMed  Google Scholar 

  20. Martino P, Raccah R, Gentile G, Venditti M, Girmenia C, Mandelli F . Aspergillus colonization of the nose and pulmonary aspergillosis in neutropenic patients: a retrospective study. Haematologica 1989; 74: 263–265.

    CAS  PubMed  Google Scholar 

  21. Leenders AC, van Belkum A, Behrendt M, Luijendijk A, Verbrugh HA . Density and molecular epidemiology of aspergillus in air and relationship to outbreaks of aspergillus infection. J Clin Microbiol 1999; 37: 1752–1757.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. de Repentigny L, Petitbois S, Boushira M, Michaliszyn E, Senechal S, Gendron N et al. Acquired immunity in experimental murine aspergillosis is mediated by macrophages. Infect Immun 1993; 6: 3791–3802.

    Google Scholar 

  23. Marr KA, Carter RA, Crippa F, Wald A, Corey L . Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002; 34: 909–917.

    Article  Google Scholar 

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Authors and Affiliations

  1. Institute for Infectious Diseases, University of Berne, Berne, Switzerland

    K Mühlemann, C Wenger & M G Täuber

  2. Department of Infectious Diseases, University Hospital Berne, Berne, Switzerland

    K Mühlemann & M G Täuber

  3. Department of Medical Oncology, University Hospital Berne, Berne, Switzerland

    R Zenhäusern

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  1. K Mühlemann
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  2. C Wenger
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  3. R Zenhäusern
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  4. M G Täuber
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Correspondence to K Mühlemann.

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Mühlemann, K., Wenger, C., Zenhäusern, R. et al. Risk factors for invasive aspergillosis in neutropenic patients with hematologic malignancies. Leukemia 19, 545–550 (2005). https://doi.org/10.1038/sj.leu.2403674

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