Invasive pulmonary aspergillosis in patients with acute leukemia

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Olfa Kassar
Aicha Ben Kahla
Yosra Fakhfakh
Wiem Feki
Fatma cheikhrouhou
Moez Elloumi

Abstract

Introduction: Invasive pulmonary aspergillosis is a serious complication in hematology.
Aim: Describe the prevalence, diagnostic aspects, therapeutic modalities, and evolution of the IPA cases occurring in patients with acute leukemia.
Methods: Our study was retrospective including patients with acute leukemia who developed invasive pulmonary aspergillosis during the period January 2009 and December 2020 at the hematology department in south Tunisia. The IPA was defined in three levels of probability according to the criteria of the EORTC / MSG 2019.
Results: We collected 127 patients who presented with Invasive pulmonary aspergillosis. Sixty-three percent of our patients had acute myeloid leukemia. The diagnosis of invasive pulmonary aspergillosis was during the induction course in 76% of cases. Twenty-seven of our patients had chest pain. The chest Computed tomography (CT) scan showed the Halo sign in 89% of cases. The Aspergillus galactomannan antigen was positive in 38% of cases. Extrapulmonary aspergillosis involvement was noted in 18% of cases: IPA was possible and probable respectively in 59% and 41% of cases. All patients treated with Voriconazole with a favorable response in 54% of cases. The mortality rate was 46%. The overall survival at week 12 was 56%.
Conclusion: The morbidity and mortality of patients who developed invasive pulmonary aspergillosis with acute leukemia in our series were high. We need to improve our strategy for early diagnosis and management.

Keywords:

Invasive pulmonary aspergillosis, acute leukemia, epidemiology, diagnosis, voriconazole

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References

  1. Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J, 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(3):265–73.
  2. Bergeron A, Porcher R, Sulahian A, De Bazelaire C, Chagnon K, Raffoux E, et al. The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies. Blood. 2012;119(8):1831–7.
  3. Baddley JW, Andes DR, Marr KA, Kontoyiannis DP, Alexander BD, Kauffman CA, et al. Factors associated with mortality in transplant patients with invasive aspergillosis. Clin Infect Dis. 2010;50(12):1559–67.
  4. Gheith S, Saghrouni F, Bannour W, Ben Youssef Y, Khelif A, Normand AC, et al. Characteristics of Invasive Aspergillosis in Neutropenic Haematology Patients (Sousse, Tunisia). Mycopathologia. 2014;177(5–6):281–9.
  5. Hadrich I, Makni F, Sellami H, Cheikhrouhou F, Sellami A, Bouaziz H, et al. Invasive aspergillosis: Epidemiology and environmental study in haematology patients (Sfax, Tunisia). Mycoses. 2010;53(5):443–7.
  6. Douglas AP, Smibert OC, Bajel A, Halliday CL, Lavee O, McMullan B, et al. Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021. Intern Med J. 2021;51(S7):143–76.
  7. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, 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) C. Clin Infect Dis. 2008;46(12):1813–21.
  8. Peter Donnelly J, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020;71(6):1367–76.
  9. Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer Consensus Criteria. Clin Infect Dis. 2008;47(5):674–83.
  10. Saghrouni F, Ben Youssef Y, Gheith S, Bouabid Z, Ben Abdeljelil J, Khammari I, et al. Twenty-nine cases of invasive aspergillosis in neutropenic patients. Med Mal Infect. 2011;41(12):657–62.
  11. Alberti C, Bouakline A, Ribaud P, Lacroix C, Rousselot P, Leblanc T, et al. Relationship between environmental fungal contamination and the incidence of invasive aspergillosis in haematology patients. J Hosp Infect. 2001;48(3):198–206.
  12. Loschi M, Thill C, Gray C, David M, Bagatha MF, Chamseddine A, et al. Invasive Aspergillosis in Neutropenic Patients During Hospital Renovation: Effectiveness of Mechanical Preventive Measures in a Prospective Cohort of 438 Patients. Mycopathologia. 2015;179(5–6):337–45.
  13. Moro ML. Epidemiology of nosocomial fungal infections. Alpe Adria Microbiol J. 1998;7(3):226–8.
  14. Barkati S, Dufresne SF, Belanger S, Vadnais B, Bergeron J, Labbe AC, et al. Incidence of invasive aspergillosis following remission-induction chemotherapy for acute leukemia: a retrospective cohort study in a single Canadian tertiary care centre. C Open. 2014;2(2):E86–93.
  15. Maertens J, Buvé K, Theunissen K, Meersseman W, Verbeken E, Verhoef G, et al. Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients. Cancer. 2009;115(2):355–62.
  16. Denning DW, Cadranel J, Beigelman-Aubry C, Ader F, Chakrabarti A, Blot S, et al. Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management. Eur Respir J [Internet]. 2016;47(1):45–68.
  17. Neofytos D, Railkar R, Mullane KM, Fredricks DN, Granwehr B, Marr KA, et al. Correlation between circulating fungal biomarkers and clinical outcome in invasive aspergillosis. PLoS One. 2015;10(6):1–13.
  18. Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;63(4):e1–60.
  19. Rudramurthy SM, Paul RA, Chakrabarti A, Mouton JW, Meis JF. Invasive aspergillosis by aspergillus flavus: Epidemiology, diagnosis, antifungal resistance, and management. J Fungi. 2019;5(3):1–23.
  20. Caillot D, Casasnovas O, Bernard A, Couaillier JF, Durand C, Cuisenier B, et al. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol. 1997;15(1):139–47.
  21. Curtis McB. A, Smith GJW, Ravin CE. Air crescent sign of invasive aspergillosis. Radiology. 1979;133(1 I):17–21.
  22. Godoy M, Viswanathan C, Marchiori E, Truong MT, Benveniste MF, Rossi S, et al. The reversed halo sign: Update and differential diagnosis. Br J Radiol. 2012;85(1017):1226–35.
  23. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102(3):433–44.
  24. Lortholary O, Gangneux JP, Sitbon K, Lebeau B, de Monbrison F, Le Strat Y, et al. Epidemiological trends in invasive aspergillosis in France: The SAIF network (2005-2007). Clin Microbiol Infect. 2011;17(12):1882–9.
  25. Marr KA, Boeckh M, Carter RA, Hyung WK, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39(6):797–802.
  26. Dragonetti G, Criscuolo M, Fianchi L, Pagano L. Invasive aspergillosis in acute myeloid leukemia: Are we making progress in reducing mortality? Med Mycol. 2017;55(1):82–6.