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Invasive Aspergillosis in Patients with Acute Leukemia: Comparison Between Acute Myeloid and Acute Lymphoid Leukemia

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Abstract

Background

The epidemiology of invasive aspergillosis (IA) in patients with acute lymphoid leukemia (ALL) has not been well characterized.

Objectives

To identify potential peculiarities in the natural history, treatment response and outcome of IA diagnosed in patients with ALL and AML.

Methods

This is a retrospective cohort study conducted in seven tertiary-care hospitals between 2009 and 2017 of all consecutive episodes of IA occurring in adult patients with acute leukemia. Demographic characteristics, underlying disease and recent treatment, antifungal prophylaxis, neutropenia, receipt of corticosteroids, clinical and radiological findings, mycological results, antifungal therapy, and 6-week and 12-week survival were recorded.

Results

We identified 77 cases of IA in 54 patients with AML and 23 patients with ALL. The majority of patients developed IA in the context of induction chemotherapy for newly diagnosed (48.0%) or relapsed (41.6%) leukemia, with no differences between ALL and AML. Lung involvement was more frequent in AML (96.3% vs. 82.6%, p = 0.06) and rhinosinusitis was more common in ALL (43.5% vs. 24.1%, p = 0.09). Galactomannan was the microbiologic documentation of IA in 76.6%, with similar patterns of positivity in AML and ALL. The 6-week survival of IA in patients with AML and ALL was 63.0% and 56.5%, respectively (p = 0.60).

Conclusions

The epidemiology, clinical presentation, diagnosis and outcome of IA in ALL patients are similar to patients with AML.

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References

  1. Nucci M, Garnica M, Gloria AB, Lehugeur DS, Dias VC, Palma LC, Cappellano P, Fertrin KY, Carlesse F, Simoes B, Bergamasco MD, Cunha CA, Seber A, Ribeiro MP, Queiroz-Telles F, Lee ML, Chauffaille ML, Silla L, de Souza CA, Colombo AL. Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil. Clin Microbiol Infect. 2013;19:745–51. https://doi.org/10.1111/1469-0691.12002.

    Article  CAS  PubMed  Google Scholar 

  2. Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, Pastore D, Picardi M, Bonini A, Chierichini A, Fanci R, Caramatti C, Invernizzi R, Mattei D, Mitra ME, Melillo L, Aversa F, Van Lint MT, Falcucci P, Valentini CG, Girmenia C, Nosari A. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75. https://doi.org/10.3324/haematol.2009.012054.

    Article  PubMed  Google Scholar 

  3. Nucci M, Anaissie E. How we treat invasive fungal diseases in patients with acute leukemia: the importance of an individualized approach. Blood. 2014;124:3858–69. https://doi.org/10.1182/blood-2014-04-516211.

    Article  CAS  PubMed  Google Scholar 

  4. Cornely OA, Leguay T, Maertens J, Vehreschild MJGT, Anagnostopoulos A, Castagnola C, Verga L, Rieger C, Kondakci M, Harter G, Duarte RF, Allione B, Cordonnier C, Heussel CP, Morrissey CO, Agrawal SG, Donnelly JP, Bresnik M, Hawkins MJ, Garner W, Gokbuget N. Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia. J Antimicrob Chemother. 2017;72:2359–67. https://doi.org/10.1093/jac/dkx133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Souza L, Nouer SA, Morales H, Simoes B, Solza C, Queiroz-Telles F, Nucci M. Epidemiology of invasive fungal disease in haematologic patients. Mycoses. 2021;64:252–6. https://doi.org/10.1111/myc.13205.

    Article  CAS  PubMed  Google Scholar 

  6. Cattaneo C, Gramegna D, Malagola M, Pagani C, Borlenghi E, Cerqui E, Passi A, Sciume M, Bernardi S, Crippa C, Dalceggio D, Carbone C, Pelizzari AM, Re A, Russo D, Rossi G. Invasive pulmonary aspergillosis in acute leukemia: a still frequent condition with a negative impact on the overall treatment outcome. Leuk Lymphoma. 2019;60:3044–50. https://doi.org/10.1080/10428194.2019.1613535.

    Article  PubMed  Google Scholar 

  7. Wang SS, Kotecha RS, Bernard A, Blyth CC, McMullan BJ, Cann MP, Yeoh DK, Bartlett AW, Ryan AL, Moore AS, Bryant PA, Clark J, Haeusler GM. Invasive fungal infections in children with acute lymphoblastic leukaemia: results from four Australian centres, 2003–2013. Pediatr Blood Cancer. 2019;66:e27915. https://doi.org/10.1002/pbc.27915.

    Article  PubMed  Google Scholar 

  8. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, Ito J, Andes DR, Baddley JW, Brown JM, Brumble LM, Freifeld AG, Hadley S, Herwaldt LA, Kauffman CA, Knapp K, Lyon GM, Morrison VA, Papanicolaou G, Patterson TF, Perl TM, Schuster MG, Walker R, Wannemuehler KA, Wingard JR, Chiller TM, Pappas PG. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50:1091–100. https://doi.org/10.1086/651263.

    Article  PubMed  Google Scholar 

  9. Hsu LY, Lee DG, Yeh SP, Bhurani D, Khanh BQ, Low CY, Norasetthada L, Chan T, Kwong YL, Vaid AK, Alejandria I, Mendoza M, Chen CY, Johnson A, Tan TY. Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study. Clin Microbiol Infect. 2015;21:594–611. https://doi.org/10.1016/j.cmi.2015.02.019.

    Article  Google Scholar 

  10. Hoenigl M, Zollner-Schwetz I, Sill H, Linkesch W, Lass-Florl C, Schnedl WJ, Krause R. Epidemiology of invasive fungal infections and rationale for antifungal therapy in patients with haematological malignancies. Mycoses. 2011;54:454–9. https://doi.org/10.1111/j.1439-0507.2010.01881.x.

    Article  CAS  PubMed  Google Scholar 

  11. Girmenia C, Raiola AM, Piciocchi A, Algarotti A, Stanzani M, Cudillo L, Pecoraro C, Guidi S, Iori AP, Montante B, Chiusolo P, Lanino E, Carella AM, Zucchetti E, Bruno B, Irrera G, Patriarca F, Baronciani D, Musso M, Prete A, Risitano AM, Russo D, Mordini N, Pastore D, Vacca A, Onida F, Falcioni S, Pisapia G, Milone G, Vallisa D, Olivieri A, Bonini A, Castagnola E, Sica S, Majolino I, Bosi A, Busca A, Arcese W, Bandini G, Bacigalupo A, Rambaldi A, Locasciulli A. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant. 2014;20:872–80. https://doi.org/10.1016/j.bbmt.2014.03.004.

    Article  PubMed  Google Scholar 

  12. Del Principe MI, Dragonetti G, Conti A, Verga L, Ballanti S, Fanci R, Candoni A, Marchesi F, Cattaneo C, Lessi F, Fracchiolla N, Spolzino A, Prezioso L, Delia M, Potenza L, Decembrino N, Castagnola C, Nadali G, Picardi M, Zama D, Orciulo E, Veggia B, Garzia M, Dargenio M, Melillo L, Manetta S, Russo D, Mancini V, Piedimonte M, Tisi MC, Toschi N, Busca A, Pagano L, behalf of the Sg, SorveglianzaEpidemiologicaInfezioninelleEmopatie g. Invasive aspergillosis in relapsed/refractory acute myeloid leukaemia patients: results from SEIFEM 2016-B survey. Mycoses. 2022;65:171–7. https://doi.org/10.1111/myc.13384.

    Article  CAS  PubMed  Google Scholar 

  13. Candoni A, Farina F, Perruccio K, Di BR, Criscuolo M, Cattaneo C, Delia M, Zannier ME, Dragonetti G, Fanci R, Martino B, Del Principe MI, Fianchi L, Vianelli N, Chierichini A, Garzia M, Petruzzellis G, Nadali G, Verga L, Busca A, Pagano L. Impact of invasive aspergillosis occurring during first induction therapy on outcome of acute myeloid leukaemia (SEIFEM-12B study). Mycoses. 2020;63:1094–100. https://doi.org/10.1111/myc.13147.

    Article  CAS  PubMed  Google Scholar 

  14. Rodriguez-Veiga R, Montesinos P, Boluda B, Lorenzo I, Martinez-Cuadron D, Salavert M, Peman J, Calvillo P, Cano I, Acuna E, Villalba A, Pinana JL, Sanz J, Solves P, Senent L, Vicente A, Sempere A, Cervera J, Barragan E, Jarque I, Torres A, Sanz MA, Sanz GF. Incidence and outcome of invasive fungal disease after front-line intensive chemotherapy in patients with acute myeloid leukemia: impact of antifungal prophylaxis. Ann Hematol. 2019;98:2081–8. https://doi.org/10.1007/s00277-019-03744-5.

    Article  CAS  PubMed  Google Scholar 

  15. Pagano L, Caira M, Candoni A, Offidani M, Martino B, Specchia G, Pastore D, Stanzani M, Cattaneo C, Fanci R, Caramatti C, Rossini F, Luppi M, Potenza L, Ferrara F, Mitra ME, Fadda RM, Invernizzi R, Aloisi T, Picardi M, Bonini A, Vacca A, Chierichini A, Melillo L, de Waure C, Fianchi L, Riva M, Leone G, Aversa F, Nosari A. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica. 2010;95:644–50. https://doi.org/10.3324/haematol.2009.012054.

    Article  PubMed  Google Scholar 

  16. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG. 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;71:1367–76. https://doi.org/10.1093/cid/ciz1008.

    Article  PubMed  Google Scholar 

  17. Girmenia C, Micozzi A, Piciocchi A, Gentile G, Di CL, Nasso D, Minotti C, Capria S, Cartoni C, Alimena G, Meloni G, Amadori S, Foa R, Venditti A. Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia. Leuk Res. 2014;38:469–74. https://doi.org/10.1016/j.leukres.2014.01.007.

    Article  PubMed  Google Scholar 

  18. Nicolato A, Nouer SA, Garnica M, Portugal R, Maiolino A, Nucci M. Invasive fungal diseases in patients with acute lymphoid leukemia. Leuk Lymphoma. 2016;57:2084–9. https://doi.org/10.3109/10428194.2016.1154957.

    Article  PubMed  Google Scholar 

  19. Delliere S, Dannaoui E, Fieux M, Bonfils P, Gricourt G, Demontant V, Podglajen I, Woerther PL, Angebault C, Botterel F. Analysis of microbiota and mycobiota in fungal ball rhinosinusitis: specific interaction between aspergillus fumigatus and haemophilus influenza? J Fungi (Basel). 2021. https://doi.org/10.3390/jof7070550.

    Article  PubMed  Google Scholar 

  20. Candoni A, Klimko N, Busca A, Di Blasi R, Shadrivova O, Cesaro S, Zannier ME, Verga L, Forghieri F, Calore E, Nadali G, Simonetti E, Muggeo P, Quinto AM, Castagnola C, Cellini M, Del Principe MI, Fracchiolla N, Melillo L, Piedimonte M, Zama D, Farina F, Giusti D, Mosna F, Capelli D, Delia M, Picardi M, Decembrino N, Perruccio K, Vallero S, Aversa F, Fanin R, Pagano L, Group S. Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases. Mycoses. 2019;62:252–60. https://doi.org/10.1111/myc.12884.

    Article  CAS  PubMed  Google Scholar 

  21. Patterson TF, Thompson GR III, Denning DW, Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Nguyen MH, Segal BH, Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR, Young JA, Bennett JE. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;63:e1–60. https://doi.org/10.1093/cid/ciw326.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B, Invasive Fungal Infections Group of the European Organisation for R, Treatment of C, The Global Aspergillus Study G. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15. https://doi.org/10.1056/NEJMoa020191.

    Article  CAS  PubMed  Google Scholar 

  23. Denning DW. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis. 1996;23:608–15. https://doi.org/10.1093/clinids/23.3.608.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Nucci M, Nouer SA, Grazziutti M, Kumar NS, Barlogie B, Anaissie E. Probable invasive aspergillosis without prespecified radiologic findings: proposal for inclusion of a new category of aspergillosis and implications for studying novel therapies. Clin Infect Dis. 2010;51:1273–80. https://doi.org/10.1086/657065.

    Article  PubMed  Google Scholar 

  26. Bergamasco MD, Pereira CAP, Arrais-Rodrigues C, Ferreira DB, Baiocchi O, Kerbauy F, Nucci M, Colombo AL. Epidemiology of invasive fungal diseases in patients with hematologic malignancies and hematopoietic cell transplantation recipients managed with an antifungal diagnostic driven approach. J Fungi (Basel). 2021. https://doi.org/10.3390/jof7080588.

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Natacha Cerchiari and Jeronimo Gerolin in the support to the data collection process. We thank COLSAN-Associaçao Beneficiente de Coleta de Sangue for the administration and accountability of the Pfizer Grant.

Funding

This work was supported by Pfizer Inc.

Author information

Authors and Affiliations

  1. Departamento de Medicina, Division of Infectious Diseases, Hospital São Paulo - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo, 669, Edifício de Pesquisas II, 5Thfloor, São Paulo, CEP 04039-032, Brazil

    Arnaldo L. Colombo & Maria Daniela Bergamasco

  2. Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 Sala 4A12, Rio de Janeiro, 21941-590, Brazil

    Simone A. Nouér & Marcio Nucci

  3. Hospital de Câncer de Barretos, Barretos, SP, Brazil

    Paulo de Tarso Oliveira e Castro

  4. Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil

    Alessandro C. Pasqualotto

  5. Department of Public Health, Universidade Federal do Paraná, Curitiba, Brazil

    Flavio de Queiroz-Telles

  6. Instituto do Cancer do Estado de São Paulo-ICESP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil

    Edson Abdala

  7. Hospital Sírio-Libanês, São Paulo, Brazil

    Jessica F. Ramos

  8. Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Diego R. Falci

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  1. Arnaldo L. Colombo
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  10. Marcio Nucci
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Contributions

ALC and MN designed the study, analyzed the data and wrote the paper; MDB, SAN, PTOC, ACP, FQT, EA, JFR and DRF performed the research and collected data.

Corresponding authors

Correspondence to Arnaldo L. Colombo or Marcio Nucci.

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Conflict of interest

Arnaldo L. Colombo (ALC) has received an Independent Investigator Grant Initiative from Pfizer that partially supported the present study. ALC also received educational grants and travel support for scientific meetings from Biotoscana-Knight, Eurofarma, United Medical, and Pfizer. Alessandro C. Pasqualotto (ACP) has received research grants from Pfizer, Gilead, and MSD. He has given paid talks and received honoraria on behalf of Pfizer, Gilead, IMMY, United Medical, MSD, Astellas, and Teva. Paulo de Tarso Oliveira e Castro has received educational grants and travel support for scientific meetings from United Medical, and Pfizer. Diego R. Falci (DRF) has received research support, payment for lectures and consulting fees from United Medical, Gilead, Astellas, MSD, IMMY and Pfizer, not related to this work. Jessica F. Ramos (JFR) has received research support, payment for lectures and consulting fees from Biotoscana-Knight, Merck Sharp and Dohme and Pfizer, not related to this work. Edson Abdala has received educational grants and travel support for scientific meetings from Biotoscana-Knight, United Medical, Abbott, Teva, MSD, Roche and Pfizer. Marcio Nucci has received honoraria for consulting and lectures from MSD, Teva, Knight, Pfizer, F2G, Takeda, Cidara, Gilead, Janssen, Abbvie, Basilea, Astellas, Abbott and Amgen. All other authors have nothing to disclose.

Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki and approved by the Ethical Committees of each participating center. Waiver of informed consent was granted by the ethical committees.

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Colombo, A.L., Bergamasco, M.D., Nouér, S.A. et al. Invasive Aspergillosis in Patients with Acute Leukemia: Comparison Between Acute Myeloid and Acute Lymphoid Leukemia. Mycopathologia 188, 1–8 (2023). https://doi.org/10.1007/s11046-022-00684-z

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