Skip to main content

Advertisement

Log in

Aspergillosis in hematopoietic stem cell transplant recipients: Risk factors, prophylaxis, and treatment

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

This article discusses newer antifungal agents, recent randomized controlled trials, and the 2008 guidelines for treatment of aspergillosis in reference to hematopoietic stem cell transplantation (HSCT). Strategies such as reduced-intensity conditioning and agents such as infliximab shed new light on aspergillosis risk. The association between Toll-like receptor polymorphisms and aspergillosis is an exciting development. Posaconazole was evaluated in two randomized prophylaxis trials, and a large, randomized trial established voriconazole’s therapeutic superiority to amphotericin. However, many questions remain regarding which patients benefit most from prophylaxis; resistance to newer antifungals; and combination, salvage, and immunomodulatory therapies. Current therapies and strategies have improved the outlook of HSCT recipients with invasive aspergillosis. Future directions include increasingly sophisticated risk stratification, clinical testing of combination therapies, and adjunctive immunomodulatory therapies.

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.

Similar content being viewed by others

References and Recommended Reading

  1. Centers for Disease Control and Prevention, Infectious Disease Society of America, American Society of Blood and Marrow Transplantation: Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Recomm Rep 2000, 49(RR-10):1–125, CE 121–127.

    Google Scholar 

  2. Walsh TJ, Anaissie EJ, Denning DW, et al.: Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008, 46:327–360.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. De Pauw B, Walsh TJ, Donnelly JP, et al.: Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008, 46:1813–1821.

    Article  PubMed  Google Scholar 

  5. van Burik JA, Carter SL, Freifeld AG, et al.: Higher risk of cytomegalovirus and aspergillus infections in recipients of T cell-depleted unrelated bone marrow: analysis of infectious complications in patients treated with T cell depletion versus immunosuppressive therapy to prevent graft-versus-host disease. Biol Blood Marrow Transplant 2007, 13:1487–1498.

    Article  PubMed  Google Scholar 

  6. 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, 42:955–963.

    Article  PubMed  CAS  Google Scholar 

  7. Garcia-Vidal C, Upton A, Kirby KA, Marr KA: Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis 2008, 47:1041–1050.

    Article  PubMed  Google Scholar 

  8. Kontoyiannis DP, Chamilos G, Lewis RE, et al.: Increased bone marrow iron stores is an independent risk factor for invasive aspergillosis in patients with high-risk hematologic malignancies and recipients of allogeneic hematopoietic stem cell transplantation. Cancer 2007, 110:1303–1306.

    Article  PubMed  Google Scholar 

  9. Fukuda T, Boeckh M, Carter RA, et al.: Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood 2003, 102:827–833.

    Article  PubMed  CAS  Google Scholar 

  10. Kojima R, Kami M, Nannya Y, et al.: Incidence of invasive aspergillosis after allogeneic hematopoietic stem cell transplantation with a reduced-intensity regimen compared with transplantation with a conventional regimen. Biol Blood Marrow Transplant 2004, 10:645–652.

    Article  PubMed  CAS  Google Scholar 

  11. Labbe AC, Su SH, Laverdiere M, et al.: High incidence of invasive aspergillosis associated with intestinal graft-versushost disease following nonmyeloablative transplantation. Biol Blood Marrow Transplant 2007, 13:1192–1200.

    Article  PubMed  Google Scholar 

  12. Mihu CN, King E, Yossepovitch O, et al.: Risk factors and attributable mortality of late aspergillosis after T-cell depleted hematopoietic stem cell transplantation. Transpl Infect Dis 2008, 10:162–167.

    Article  PubMed  CAS  Google Scholar 

  13. Mossad SB, Avery RK, Bolwell BJ: Importance of antifungal prophylaxis in patients who received a nonmyeloablative allogeneic PBSC transplant. Clin Infect Dis 2003, 36:1503–1504; author reply 1504.

    Article  PubMed  Google Scholar 

  14. Mossad SB, Avery RK, Longworth DL, et al.: Infectious complications within the first year after nonmyeloablative allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant 2001, 28:491–495.

    Article  PubMed  CAS  Google Scholar 

  15. Marty FM, Lee SJ, Fahey MM, et al.: Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Blood 2003, 102:2768–2776.

    Article  PubMed  CAS  Google Scholar 

  16. Bochud PY, Chien JW, Marr KA, et al.: Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med 2008, 359:1766–1777.

    Article  PubMed  CAS  Google Scholar 

  17. Kesh S, Mensah NY, Peterlongo P, et al.: TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann N Y Acad Sci 2005, 1062:95–103.

    Article  PubMed  CAS  Google Scholar 

  18. Nucci M, Biasoli I, Akiti T, et al.: A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients. Clin Infect Dis 2000, 30:300–305.

    Article  PubMed  CAS  Google Scholar 

  19. Oren I, Rowe JM, Sprecher H, et al.: A prospective randomized trial of itraconazole vs fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2006, 38:127–134.

    Article  PubMed  CAS  Google Scholar 

  20. Glasmacher A, Prentice AG: Evidence-based review of antifungal prophylaxis in neutropenic patients with haematological malignancies. J Antimicrob Chemother 2005, 56(Suppl 1):i23–i32.

    Article  PubMed  CAS  Google Scholar 

  21. 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, 96:2055–2061.

    PubMed  CAS  Google Scholar 

  22. van Burik JA, Ratanatharathorn V, Stepan DE, et al.: Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 2004, 39:1407–1416.

    Article  PubMed  Google Scholar 

  23. Madureira A, Bergeron A, Lacroix C, et al.: Breakthrough invasive aspergillosis in allogeneic haematopoietic stem cell transplant recipients treated with caspofungin. Int J Antimicrob Agents 2007, 30:551–554.

    Article  PubMed  CAS  Google Scholar 

  24. Schwartz S, Behre G, Heinemann V, et al.: Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial. Blood 1999, 93:3654–3661.

    PubMed  CAS  Google Scholar 

  25. Alexander BD, Dodds Ashley ES, Addison RM, et al.: Non-comparative evaluation of the safety of aerosolized amphotericin B lipid complex in patients undergoing allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2006, 8:13–20.

    Article  PubMed  CAS  Google Scholar 

  26. Cornely OA, Maertens J, Winston DJ, et al.: Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007, 356:348–359.

    Article  PubMed  CAS  Google Scholar 

  27. Ullmann AJ, Lipton JH, Vesole DH, et al.: Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007, 356:335–347.

    Article  PubMed  CAS  Google Scholar 

  28. Mullane K, Toor AA, Kalnicky C, et al.: Posaconazole salvage therapy allows successful allogeneic hematopoietic stem cell transplantation in patients with refractory invasive mold infections. Transpl Infect Dis 2007, 9:89–96.

    Article  PubMed  CAS  Google Scholar 

  29. Raad, II, Hanna HA, Boktour M, et al.: Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin. Leukemia 2008, 22:496–503.

    Article  PubMed  CAS  Google Scholar 

  30. Walsh TJ, Raad I, Patterson TF, et al.: Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis 2007, 44:2–12.

    Article  PubMed  CAS  Google Scholar 

  31. van Burik JA, Hare RS, Solomon HF, et al.: Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis 2006, 42:e61–e65.

    Article  PubMed  Google Scholar 

  32. Raad, II, Hachem RY, Herbrecht R, et al.: Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis 2006, 42:1398–1403.

    Article  PubMed  CAS  Google Scholar 

  33. Cornely OA, Bohme A, Buchheidt D, et al.: Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica 2009, 94:113–122.

    Article  PubMed  Google Scholar 

  34. Leather HL, Wingard JR: New strategies of antifungal therapy in hematopoietic stem cell transplant recipients and patients with hematological malignancies. Blood Rev 2006, 20:267–287.

    Article  PubMed  CAS  Google Scholar 

  35. Siegel JD, Rhinehart E, Jackson M, Chiarello L: 2007 Guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control 2007, 35(10 Suppl 2):S65–S164.

    Article  PubMed  Google Scholar 

  36. Boyce JM, Pittet D: Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep 2002, 51(RR-16):1–45, quiz CE 41–44.

    PubMed  Google Scholar 

  37. Rutala WA, Weber DJ, Healthcare Infection Control Practices Advisory Committee (HICPAC): Guideline for disinfection and sterilization in healthcare facilities, 2008. Available at http://www.cdc.gov/ncidod/dhqp/pdf/guidelines/Disinfection_Nov_2008.pdf. Accessed December 2008.

  38. Sehulster L, Chinn RY: Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep 2003, 52(RR-10):1–42.

    PubMed  Google Scholar 

  39. Herbrecht R, Denning DW, Patterson TF, et al.: Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002, 347:408–415.

    Article  PubMed  CAS  Google Scholar 

  40. Ito JI, Chandrasekar PH, Hooshmand-Rad R. Effectiveness of amphotericin B lipid complex (ABLC) treatment in allogeneic hematopoietic cell transplant (HCT) recipients with invasive aspergillosis (IA). Bone Marrow Transplant 2005, 36:873–877.

    Article  PubMed  CAS  Google Scholar 

  41. Kontoyiannis DP, Ratanatharathorn V, Young JA, et al.: Micafungin alone or in combination with other systemic antifungal therapies in hematopoietic stem cell transplant recipients with invasive aspergillosis. Transpl Infect Dis 2009, 11:89–93.

    Article  PubMed  CAS  Google Scholar 

  42. Marty FM, Lowry CM, Cutler CS, et al.: Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006, 12:552–559.

    Article  PubMed  CAS  Google Scholar 

  43. Conlon JD, Dauenhauer M, Tonkovic-Capin V, et al.: Voriconazole-induced blistering in the setting of graft versus host disease: A report of 2 patients. J Am Acad Dermatol 2008, 58:484–487.

    Article  PubMed  Google Scholar 

  44. Trifilio S, Singhal S, Williams S, et al.: Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole. Bone Marrow Transplant 2007, 40:451–456.

    Article  PubMed  CAS  Google Scholar 

  45. Kontoyiannis DP, Lionakis MS, Lewis RE, 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, 191:1350–1360.

    Article  PubMed  Google Scholar 

  46. Johnson MD, Perfect JR: Combination antifungal therapy: what can and should we expect? Bone Marrow Transplant 2007, 40:297–306.

    Article  PubMed  CAS  Google Scholar 

  47. Leather HL, Wingard JR: Is combination antifungal therapy for invasive aspergillosis a necessity in hematopoietic stem-cell transplant recipients? Curr Opin Infect Dis 2006, 19:371–379.

    Article  PubMed  Google Scholar 

  48. Kontoyiannis DP, Hachem R, Lewis RE, et al.: Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer 2003, 98:292–299.

    Article  PubMed  CAS  Google Scholar 

  49. Safdar A, Rodriguez G, Rolston KV, et al.: High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation. Bone Marrow Transplant 2007, 39:157–164.

    Article  PubMed  CAS  Google Scholar 

  50. Segal BH, Kwon-Chung J, Walsh TJ, et al.: Immunotherapy for fungal infections. Clin Infect Dis 2006, 42:507–515.

    Article  PubMed  CAS  Google Scholar 

  51. Safdar A: Strategies to enhance immune function in hematopoietic transplantation recipients who have fungal infections. Bone Marrow Transplant 2006, 38:327–337.

    Article  PubMed  CAS  Google Scholar 

  52. Safdar A, Rodriguez GH, Lichtiger B, et al.: Recombinant interferon gamma1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions. Cancer 2006, 106: 2664–2671.

    Article  PubMed  CAS  Google Scholar 

  53. Safdar A, Rodriguez G, Ohmagari N, et al.: The safety of interferon-gamma-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation. Cancer 2005, 103:731–739.

    Article  PubMed  CAS  Google Scholar 

  54. Price TH, Bowden RA, Boeckh M, et al.: Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation. Blood 2000, 95:3302–3309.

    PubMed  CAS  Google Scholar 

  55. Perruccio K, Tosti A, Burchielli E, et al.: Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood 2005, 106:4397–4406.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robin K. Avery.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Avery, R.K. Aspergillosis in hematopoietic stem cell transplant recipients: Risk factors, prophylaxis, and treatment. Curr Infect Dis Rep 11, 223–228 (2009). https://doi.org/10.1007/s11908-009-0033-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-009-0033-3

Keywords

Navigation