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A Prospective Observational Multi-institutional Study on Invasive Fungal Infections Following Chemotherapy for Acute Myeloid Leukemia (MISFIC Study): A Real World Scenario from India

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Abstract

We performed a prospective multi-centre observational study to understand the incidence of IFI in patients with AML in India with use of anti-fungal prophylaxis. All patients with AML receiving either induction chemotherapy or salvage chemotherapy between November 2014 and February 2016 were included in this prospective observational study from 10 Indian centres. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy used, type of anti-fungal prophylaxis used, time to neutrophil recovery, incidence of IFI and survival were collected. Two hundred patients (118 male and 82 females) with a median age of 35 years (range: 2–66) were recruited. One hundred and eighty-six (93%) had newly diagnosed acute myeloid leukemia (AML) while 14 (7%) had relapsed disease. IFI occurred in 53 patients (26.5%) with proven or probable IFI occurring in 17 (8.5%). Use of posaconazole prophylaxis (p = 0.027) was the only factor found to be associated with a reduced incidence of IFI. The overall survival (OS) at 6 weeks and 3 months respectively was similar among patients who had IFI (83.0 ± 5.2%; 81.0 ± 5.4%) as compared to those without IFI (84.4 + 3.0%; 81.4 ± 3.2%). This prospective study reveals a high incidence of IFI in patients undergoing chemotherapy for AML in India. The use of posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal strategies to prevent IFI need to be studied.

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References

  1. Auberger J, Lass-Florl C, Ulmer H et al (2008) Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int J Hematol 88(5):508–515

    Article  Google Scholar 

  2. Caira M, Candoni A, Verga L et al (2015) Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010—a multicenter study). Haematologica 100(2):284–292

    Article  Google Scholar 

  3. Gomes MZR, Mulanovich VE, Jiang Y, Lewis RE, Kontoyiannis DP (2014) Incidence density of invasive fungal infections during primary antifungal prophylaxis in newly diagnosed acute myeloid leukemia patients in a tertiary cancer center, 2009 to 2011. Antimicrob Agents Chemother 58(2):865–873

    Article  Google Scholar 

  4. Girmenia C, Micozzi A, Piciocchi A et al (2014) Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia. Leuk Res 38(4):469–474

    Article  Google Scholar 

  5. Michallet M, Bénet T, Sobh M et al (2012) Invasive aspergillosis: an important risk factor on the short- and long-term survival of acute myeloid leukemia (AML) patients. Eur J Clin Microbiol Infect Dis 31(6):991–997

    Article  CAS  Google Scholar 

  6. Tang JL, Kung HC, Lei WC et al (2015) High incidences of invasive fungal infections in acute myeloid leukemia patients receiving induction chemotherapy without systemic antifungal prophylaxis: a prospective observational study in Taiwan. PLoS ONE 10(6):e0128410

    Article  Google Scholar 

  7. Cho SY, Lee DG, Choi SM et al (2015) Posaconazole for primary antifungal prophylaxis in patients with acute myeloid leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a single-centre retrospective study in Korea and clinical considerations. Mycoses 58(9):565–571

    Article  CAS  Google Scholar 

  8. Korula A, Abraham A, Abubacker FN, Viswabandya A, Lakshmi KM, Abraham OC, Rupali P, Varghese GM, Michael JS, Srivastava A, Mathews V, George B (2017) Invasive fungal infection following chemotherapy for acute myeloid leukaemia—experience from a developing country. Mycoses 60(10):686–691

    Article  CAS  Google Scholar 

  9. Cornely OA, Maertens J, Winston DJ et al (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356(4):348–359

    Article  CAS  Google Scholar 

  10. Barreto JN, Beach CL, Wolf RC et al (2013) The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole. Am J Hematol 88:283–288

    Article  CAS  Google Scholar 

  11. Ananda-Rajah MR, Grigg A, Downey MT et al (2012) Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12- year period. Haematologica 97(3):459–463

    Article  CAS  Google Scholar 

  12. Malhotra P, Makkar A, Guru Murthy GS et al (2014) Empirical amphotericin B therapy on day 4 or day 8 of febrile neutropenia. Mycoses 57(2):110–115

    Article  CAS  Google Scholar 

  13. Freifeld AG, Bow EJ, Sepkowitz KA et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52(4):e56–e93

    Article  Google Scholar 

  14. Cornely OA, Cuenca-Estrella M, Meis JF et al (2014) European Society of Clinical Microbiology and Infectious Diseases (ESCMID) fungal infection study group (EFISG) and European Confederation of Medical Mycology (ECMM) 2013 joint guidelines on diagnosis and management of rare and emerging fungal diseases. Clin Microbiol Infect 20:1–4

    Article  Google Scholar 

  15. Tissot F, Agrawal S, Pagano L et al (2017) ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 102(3):433–444

    Article  Google Scholar 

  16. Hsu LY, Lee DG, Yeh SP et al (2015) Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study. Clin Microbiol Infect. https://doi.org/10.1016/j.cmi.2015.02.019

    Article  PubMed  Google Scholar 

  17. Jha AK, Bansal D, Chakrabarti A, Shivaprakash MR, Trehan A, Marwaha RK (2013) Serum galactomannan assay for the diagnosis of invasive aspergillosis in children with haematological malignancies. Mycoses 56(4):442–448

    Article  CAS  Google Scholar 

  18. De Pauw B, Walsh TJ, Donnelly JP et al (2008) 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 46(12):1813–1821

    Article  Google Scholar 

  19. van de Peppel RJ, Visser LG, Dekkers OM, de Boer MGJ (2018) The burden of Invasive Aspergillosis in patients with haematological malignancy: a meta-analysis and systematic review. J Infect 76(6):550–562

    Article  Google Scholar 

  20. Soyer N, Kiper Ünal HD, Vural F, Şahin F, Töbü M, Dönmez A, Tombuloğlu M, Arda B, Saydam G (2017) Epidemiology and analysis of invasive fungal infections in patients with hematological malignancies: a single-center real-life experience. Turk J Med Sci 47(5):1535–1542

    Article  CAS  Google Scholar 

  21. Tormo M, Pérez-Martínez A, Calabuig M, Hernández-Boluda JC, Amat P, Navarro D, Solano C (2018) Primary prophylaxis of invasive fungal infections with posaconazole or itraconazole in patients with acute myeloid leukaemia or high-risk myelodysplastic syndromes undergoing intensive cytotoxic chemotherapy: a real-world comparison. Mycoses 61(3):206–212

    Article  CAS  Google Scholar 

  22. Dahlén T, Kalin M, Cederlund K, Nordlander A, Björkholm M, Ljungman P, Blennow O (2016) Decreased invasive fungal disease but no impact on overall survival by posaconazole compared to fluconazole prophylaxis: a retrospective cohort study in patients receiving induction therapy for acute myeloid leukaemia/myelodysplastic syndromes. Eur J Haematol 96(2):175–180

    Article  Google Scholar 

  23. Lee CH, Lin C, Ho CL, Lin JC (2018) Primary fungal prophylaxis in haematological malignancy: a network meta-analysis of randomized controlled trials. Antimicrob Agents Chemother. https://doi.org/10.1128/aac.00355-18

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was funded through an education grant from Merck, Sharpe and Dome (MSD).

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Correspondence to Biju George.

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All research involving human participants was performed as per the guidelines established by the Helsinki declaration. All participating institutions obtained ethical clearance from their respective institutions before starting the trial.

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George, B., Menon, H., Bhurani, D. et al. A Prospective Observational Multi-institutional Study on Invasive Fungal Infections Following Chemotherapy for Acute Myeloid Leukemia (MISFIC Study): A Real World Scenario from India. Indian J Hematol Blood Transfus 36, 97–103 (2020). https://doi.org/10.1007/s12288-019-01173-y

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  • DOI: https://doi.org/10.1007/s12288-019-01173-y

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