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Overview of Invasive Fungal Disease in Oncology Patients

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Principles and Practice of Cancer Infectious Diseases

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

The spectrum of invasive fungal disease has changed considerably in the past 2 decade. Since early 1990s, triazole prophylaxis has resulted in a significant decline in cases of invasive candidiasis among patients undergoing hematopoietic stem cell transplantation and those with acute leukemia. Recently, reduced rates of invasive mold disease following echinocandin and antimold triazoles use during the high-risk periods have ushered optimism. This trend in effective drug-mediated prevention has not been without setbacks including unexpected toxicity due to drug–drug interaction, and difficult-to-treat breakthrough fungal disease due to previously uncommon yeasts and filamentous fungi. The rise in virulent non-albicans Candida species and non-Aspergillus molds has, to some extent, compromised the recent advances in early diagnosis and effective antifungal therapy. As the understanding of hosts’ genetic (polymorphisms) vulnerability to fungal ­disease improves, next generation of diagnostic assays (DNA proliferation, microarray and other technologies) gain ­clinical validation, approach toward mitigating underlying immune defects with recombinant cytokines, strategies to restore innate and adaptive immune dysfunction become feasible, and target-specific effective antineoplastic therapy is introduced in the cancer fighting armamentarium; these accomplishments in a new era for improved outcomes in cancer patients who are susceptible to invasive fungal disease.

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References

  1. Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992;326:845–51.

    Article  PubMed  CAS  Google Scholar 

  2. Wingard JR, Merz WG, Rinaldi MG, Johnson TR, Karp JE, Saral R. Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med. 1991;325:1274–7.

    Article  PubMed  CAS  Google Scholar 

  3. Safdar A, van Rhee F, Henslee-Downey JP, Singhal S, Mehta J. Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. Bone Marrow Transplant. 2001;28:873–8.

    Article  PubMed  CAS  Google Scholar 

  4. Horn DL, Neofytos D, Anaissie EJ, et al. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis. 2009;48:1695–703.

    Article  PubMed  CAS  Google Scholar 

  5. van Burik JA, Ratanatharathorn V, Stepan DE, Miller CB, Lipton JH, Vesole DH, et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. 2004;39:1407–16.

    Article  PubMed  Google Scholar 

  6. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356:348–59.

    Article  PubMed  CAS  Google Scholar 

  7. Marty FM, Cosimi LA, Baden LR. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med. 2004;350:950–2.

    Article  PubMed  CAS  Google Scholar 

  8. Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005;191:1350–60.

    Article  PubMed  Google Scholar 

  9. Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351:1391–402.

    Article  PubMed  CAS  Google Scholar 

  10. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347:2020–9.

    Article  PubMed  CAS  Google Scholar 

  11. Pappas PG, Rotstein CM, Betts RF, Nucci M, Talwar D, De Waele JJ, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007;45:883–93.

    Article  PubMed  CAS  Google Scholar 

  12. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15.

    Article  PubMed  CAS  Google Scholar 

  13. Neofytos D, Horn D, Anaissie E, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis. 2009;48:265–73.

    Article  PubMed  CAS  Google Scholar 

  14. Upton A, Kirby KA, Carpenter P, et al. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis. 2007;44:531–40.

    Article  PubMed  Google Scholar 

  15. Nivoix Y, Velten M, Letscher-Bru V, et al. Factors associated with overall and attributable mortality in invasive aspergillosis. Clin Infect Dis. 2008;47:1176–84.

    Article  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Lamaris GA, Lewis RE, Chamilos G, et al. Caspofungin mediated b-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hypae. J Infect Dis. 2008;198:186–92.

    Article  PubMed  CAS  Google Scholar 

  18. Hohl TM, Feldmesser M, Perlin DS, Pamer EG. Caspofungin modulates inflammatory responses to Aspergillus fumigatus through stage-specific effects on fungal b-glucan exposure. J Infect Dis. 2008;198:176–85.

    Article  PubMed  CAS  Google Scholar 

  19. Plantinga TS, van der Velden WJ, Ferwerda B, et al. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009;49:724–32.

    Article  PubMed  CAS  Google Scholar 

  20. Bochud PY, Chien JW, Marr KA, et al. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med. 2008;359:1766–77.

    Article  PubMed  CAS  Google Scholar 

  21. Carvalho A, Cunha C, Carotti A, et al. Polymorphisms in Toll-like receptor genes and susceptibility to infections in allogeneic stem cell transplantation. Exp Hematol. 2009;37:1022–9.

    Article  PubMed  CAS  Google Scholar 

  22. Ferwerda B, McCall MB, Alonso S, et al. TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proc Natl Acad Sci USA. 2007;104:16645–50.

    Article  PubMed  Google Scholar 

  23. Seo KW, Kim DH, Sohn SK, et al. Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation. Bone Marrow Transplant. 2005;36:1089–95.

    Article  PubMed  CAS  Google Scholar 

  24. Sainz J, Perez E, Hassan L, et al. Variable number of tandem repeats of TNF receptor type 2 promoter as genetic biomarker of susceptibility to develop invasive pulmonary aspergillosis. Hum Immunol. 2007;68:41–50.

    Article  PubMed  CAS  Google Scholar 

  25. Zaas AK, Liao G, Chien JW, et al. Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS Genet. 2008;4:e1000101.

    Article  PubMed  Google Scholar 

  26. Safdar A. Difficulties with fungal infections in acute myelogenous leukemia patients: immune enhancement strategies. Oncologist. 2007;12 Suppl 2:2–6.

    PubMed  CAS  Google Scholar 

  27. Safdar A. Strategies to enhance immune function in hematopoietic transplantation recipients who have fungal infections. Bone Marrow Transplant. 2006;38(5):327–37.

    Article  PubMed  CAS  Google Scholar 

  28. Safdar A. Immunomodulation therapy for invasive aspergillosis – discussion on myeloid growth factors, recombinant cytokines and antifungal drug immune modulation. Curr Fungal Infect Rep. 2010;4:1–7.

    Article  PubMed  Google Scholar 

  29. Freireich EJ, Levin RH, Whang J, Carbone PP, Bronson W, Morse EE. The function and face of transfused leukocytes from donors with chronic myelocytic leukemia in leukopenic recipients. Ann NY Acad Sci. 1964;113:1081–90.

    Article  PubMed  CAS  Google Scholar 

  30. Seidel MG, Peters C, Wacker A, Northoff H, Moog R, Boehme A, et al. Randomized phase III study of granulocyte transfusions in neutropenic patients. Bone Marrow Transplant. 2008;42(10):679–84.

    Article  PubMed  CAS  Google Scholar 

  31. Safdar A, Rodriguez G, Ohmagari N, Kontoyiannis DP, Rolston KV, Raad II, et al. The safety of interferon-gamma-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation. Cancer. 2005;103:731–9.

    Article  PubMed  CAS  Google Scholar 

  32. Gil-Lamaignere C, Winn RM, Simitsopoulou M, Maloukou A, Walsh TJ, Roilides E. Inteferon gamma and granulocyte-­macrophage colony-stimulating factor augment the antifungal activity of human polymorphonuclear leukocytes against Scedosporium spp.: comparison with Aspergillus spp. Med Mycol. 2005;43:253–60.

    Article  PubMed  CAS  Google Scholar 

  33. Dignani MC, Rex JH, Chan KW, Dow G, deMagalhaes-Silverman M, Maddox A, et al. Immunomodulation with interferon-gamma and colony-stimulating factors for refractory fungal infections in patients with leukemia. Cancer. 2005;104:199–204.

    Article  PubMed  CAS  Google Scholar 

  34. Tramsen L, Beck O, Schuster FR, et al. Generation and characterization of anti-Candida T cells as potential immunotherapy in patients with Candida infection after allogeneic hematopoietic stem-cell transplant. J Infect Dis. 2007;196:485–92.

    Article  PubMed  CAS  Google Scholar 

  35. Tramsen L, Koehl U, Tonn T, et al. Clinical-scale generation of human anti-Aspergillus T cells for adoptive immunotherapy. Bone Marrow Transplant. 2009;43:13–9.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Amar Safdar .

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Safdar, A. (2011). Overview of Invasive Fungal Disease in Oncology Patients. In: Safdar, A. (eds) Principles and Practice of Cancer Infectious Diseases. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-644-3_22

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  • DOI: https://doi.org/10.1007/978-1-60761-644-3_22

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  • Publisher Name: Humana Press, Totowa, NJ

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