Skip to main content
SpringerLink
Log in

Antifungal prophylaxis during 7 + 3 induction chemotherapy for acute myeloid leukemia is associated with improved survival, in a setting with low incidence of invasive mold infections

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myeloid leukemia (AML). In this patient population, antifungal prophylaxis (AP) has been associated with decreased incidence of IFIs and better survival. However, some centers have not adopted AP during induction chemotherapy for AML, as it is unclear whether AP improves outcomes in settings where the incidence of invasive mold infections is low. We retrospectively assessed the differences in clinical outcomes and resource utilization in patients undergoing 7 + 3 induction chemotherapy for AML, after implementing a policy of AP as part of a dedicated inpatient malignant hematology service (HS) at Rhode Island Hospital. Between January 1, 2007 and April 1, 2019, 56 patients with AML received AP during 7 + 3 induction chemotherapy and 52 patients did not, without significant differences in their baseline characteristics. Use of AP was associated with less proven or probable IFI (0% vs. 6%, P = 0.1) and lower all-cause in-hospital mortality (7% vs. 21%, P < 0.05), without significant increases in resource utilization or toxicities. Empiric and targeted antifungal therapies were more frequently started in the non-AP group (69%) than changed in the AP group (41%, P < 0.005). Having a dedicated inpatient malignant hematology service was also associated with improved outcomes. However, use of AP was associated with better survival (30-day post-induction survival log-rank P < 0.05), prior to the implementation of this clinical service as well, which is suggestive of an independent benefit from AP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Halpern AB, Lyman GH, Walsh TJ, Kontoyiannis DP, Walter RB (2015) Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia. Blood 126(26):2790–2797. https://doi.org/10.1182/blood-2015-07-627323

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356(4):348–359. https://doi.org/10.1056/NEJMoa061094

    Article  PubMed  CAS  Google Scholar 

  3. Lupianez CB, Canet LM, Carvalho A, Alcazar-Fuoli L, Springer J, Lackner M, Segura-Catena J, Comino A, Olmedo C, Rios R, Fernandez-Montoya A, Cuenca-Estrella M, Solano C, Lopez-Nevot MA, Cunha C, Oliveira-Coelho A, Villaescusa T, Fianchi L, Aguado JM, Pagano L, Lopez-Fernandez E, Potenza L, Luppi M, Lass-Florl C, Loeffler J, Einsele H, Vazquez L, Group PS, Jurado M, Sainz J (2015) Polymorphisms in host immunity-modulating genes and risk of invasive aspergillosis: results from the AspBIOmics consortium. Infect Immun 84(3):643–657. https://doi.org/10.1128/IAI.01359-15

    Article  PubMed  CAS  Google Scholar 

  4. Network NCC (2020) Prevention and Treatment of Cancer-Related Infections (Version 1.2020). http://www.nccn.org/professionals/physician_gls/pdf/infections.pdf. Accessed Feb 17 2020

  5. Maertens JA, Girmenia C, Bruggemann RJ, Duarte RF, Kibbler CC, Ljungman P, Racil Z, Ribaud P, Slavin MA, Cornely OA, Peter Donnelly J, Cordonnier C, European Conference on Infections in Leukaemia ajvotEGfB, Marrow Transplantation tEOfR, Treatment of Cancer tIHSa, European Conference on Infections in Leukaemia ajvotEGfB, Marrow Transplantation tEOfR, Treatment of Cancer tIHS, the European L (2018) European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia. J Antimicrob Chemother 73 (12):3221–3230. https://doi.org/10.1093/jac/dky286

  6. De Pauw BE, Donnelly JP (2007) Prophylaxis and aspergillosis--has the principle been proven? N Engl J Med 356(4):409–411. https://doi.org/10.1056/NEJMe068266

    Article  PubMed  Google Scholar 

  7. Hammond SP, Marty FM, Bryar JM, DeAngelo DJ, Baden LR (2010) Invasive fungal disease in patients treated for newly diagnosed acute leukemia. Am J Hematol 85(9):695–699. https://doi.org/10.1002/ajh.21776

    Article  PubMed  Google Scholar 

  8. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE, European Organization for R, Treatment of Cancer/Invasive Fungal Infections Cooperative G, National Institute of A, Infectious Diseases Mycoses Study Group Consensus G (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. https://doi.org/10.1086/588660

    Article  PubMed  PubMed Central  Google Scholar 

  9. Network NCC (2020) Acute myeloid leukemia (Version 3.2020). https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed Feb 17 2020

  10. Foundation ABoIM (2012) Choosing wisely: EKGs and exercise stress tests. American Board of Internal Medicine Foundation, Washington, DC

  11. Pagano L, Caira M, Candoni A, Aversa F, Castagnola C, Caramatti C, Cattaneo C, Delia M, De Paolis MR, Di Blasi R, Di Caprio L, Fanci R, Garzia M, Martino B, Melillo L, Mitra ME, Nadali G, Nosari A, Picardi M, Potenza L, Salutari P, Trecarichi EM, Tumbarello M, Verga L, Vianelli N, Busca A, Group S (2012) Evaluation of the practice of antifungal prophylaxis use in patients with newly diagnosed acute myeloid leukemia: results from the SEIFEM 2010-B registry. Clin Infect Dis 55(11):1515–1521. https://doi.org/10.1093/cid/cis773

    Article  PubMed  CAS  Google Scholar 

  12. Nomura K, Kawasugi K, Morimoto T (2006) Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy. Eur J Cancer Care 15(1):44–50. https://doi.org/10.1111/j.1365-2354.2005.00618.x

    Article  CAS  Google Scholar 

  13. Busca A, Lessi F, Verga L, Candoni A, Cattaneo C, Cesaro S, Dragonetti G, Delia M, De Luca A, Guglielmi G, Tumbarello M, Martino G, Nadali G, Fanci R, Picardi M, Potenza L, Nosari A, Aversa F, Pagano L, on the behalf of the SG (2017) SEIFEM 2010-E: economic evaluation of posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia receiving induction chemotherapy. Leuk Lymphoma 58(12):2859–2864. https://doi.org/10.1080/10428194.2017.1318438

    Article  PubMed  CAS  Google Scholar 

  14. Lundberg J, Hoglund M, Bjorkholm M, Akerborg O (2014) Economic evaluation of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infection in high-risk neutropenic patients in Sweden. Clin Drug Investig 34(7):483–489. https://doi.org/10.1007/s40261-014-0199-9

    Article  PubMed  Google Scholar 

  15. Cho SY, Lee DG, Choi JK, Lee HJ, Kim SH, Park SH, Choi SM, Choi JH, Yoo JH, Kim YJ, Kim HJ, Min WS, Back H, Kang S, Lee EK (2015) Cost-benefit analysis of posaconazole versus fluconazole or itraconazole as a primary antifungal prophylaxis in high-risk hematologic patients: a propensity score-matched analysis. Clin Ther 37(9):2019–2027. https://doi.org/10.1016/j.clinthera.2015.06.014

    Article  PubMed  Google Scholar 

  16. Camara R, Gozalbo I, Jurado M, Sanz J, Aragon B, Grau S (2017) Cost-effectiveness of posaconazole tablets for invasive fungal infections prevention in acute myelogenous leukemia or myelodysplastic syndrome patients in Spain. Adv Ther 34(9):2104–2119. https://doi.org/10.1007/s12325-017-0600-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Hillner BE, Smith TJ, Desch CE (2000) Hospital and physician volume or specialization and outcomes in cancer treatment: importance in quality of cancer care. J Clin Oncol 18(11):2327–2340. https://doi.org/10.1200/JCO.2000.18.11.2327

    Article  PubMed  CAS  Google Scholar 

  18. Giri S, Pathak R, Aryal MR, Karmacharya P, Bhatt VR, Martin MG (2015) Impact of hospital volume on outcomes of patients undergoing chemotherapy for acute myeloid leukemia: a matched cohort study. Blood 125(21):3359–3360. https://doi.org/10.1182/blood-2015-01-625764

    Article  PubMed  CAS  Google Scholar 

  19. Zeidan AMPN, Wang X et al (2019) Patterns of care and clinical outcomes with 7+3 induction chemotherapy for patients (pts) with acute myeloid leukemia (AML) in the United States (US): a large population-based study. Blood 134(116)

Download references

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Andrew Hsu & John L. Reagan

  2. Division of Hematology/Oncology, Rhode Island Hospital, Lifespan Cancer Institute, Providence, RI, USA

    Andrew Hsu & John L. Reagan

  3. Department of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Robert Matera

  4. Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Kendra Vieira & Dimitrios Farmakiotis

Authors
  1. Andrew Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Matera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kendra Vieira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John L. Reagan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dimitrios Farmakiotis
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AH, RM, KV, JLR, and DF all helped write and revise the manuscript. AH and RM verified and extracted the data. AH, JLR, and DF analyzed the data. AH and DF created tables and figures.

Corresponding author

Correspondence to Andrew Hsu.

Ethics declarations

Conflict of interest

Farmakiotis: Astellas: Research Funding; Viracor-Eurofins: Consultancy, Research Funding.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hsu, A., Matera, R., Vieira, K. et al. Antifungal prophylaxis during 7 + 3 induction chemotherapy for acute myeloid leukemia is associated with improved survival, in a setting with low incidence of invasive mold infections. Support Care Cancer 29, 707–712 (2021). https://doi.org/10.1007/s00520-020-05535-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-020-05535-5

Keywords

Search

Navigation