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A retrospective study evaluating the impact of infectious complications during azacitidine treatment

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Abstract

Azacitidine has become an available therapy for high-risk myelodysplastic syndromes. Infectious complications (IC) may impede the success of therapy. Since most patients are managed in an outpatient setting, often with low level of clinical and microbiological documentation, the impact of IC remains unclear. We retrospectively evaluated the clinical course of 77 patients with MDS treated with azacitidine between 2004 and 2015 (median age 69 years). Clinical workup included severity and type of IC, days in the hospital and with antimicrobial therapy, response to azacitidine, and overall survival (OS). In total, 614 azacitidine cycles were administered, 81 cycles with at least one IC. The median number of administered cycles was 6 (range 1–43). Median OS after the start of azacitidine was 17 months (range 1–103). Infection rates were higher in the first 3 cycles with bacterial infections leading. The better patients’ hematological response to azacitidine with less IC occurred, and fewer days with antimicrobial treatment were needed. Compared to progressive disease, stable disease made no significant improvement in occurrence of IC and days in the hospital. Older age was associated with more IC and longer time in the hospital. Comorbidities or IPSS-R had no influence on IC. The incidence of IC correlated with hematological response and age. Stable disease led to longer OS, but incidence of IC was comparable to progressive disease and survival seemed to be bought by a considerable number of IC. IC rates were highest in the first 3 cycles. We recommend response evaluation after 4–6 cycles.

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References

  1. Kuendgen A, Strupp C, Aivado M et al (2006) Myelodysplastic syndromes in patients younger than age 50. J Clin Oncol 24:5358–5365

    Article  PubMed  Google Scholar 

  2. Xicoy B, Jiménez M, García et al (2013) Results of treatment with azacitidine in patients aged ≥75 years included in the Spanish Registry of Myelodysplastic Syndromes. Leuk Lymphoma 55:1300–1303

    Article  PubMed  Google Scholar 

  3. Germing U, Kobbe G, Haas R et al (2013) Myelodysplastic syndromes: diagnosis, prognosis, and treatment. Dtsch Arztebl Int 110:783–790

    PubMed  PubMed Central  Google Scholar 

  4. Neukirchen J, Lauseker M, Blum S et al (2014) Validation of the revised International Prognostic Scoring System (IPSS-R) in patients with myelodysplastic syndrome: a multicenter study. Leuk Res 38:57–64

    Article  PubMed  Google Scholar 

  5. Greenberg PL, Tuechler H, Schanz J et al (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120:2454–2465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kaminskas E, Farrell AT, Wang YC et al (2005) FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist 10:176–182

    Article  CAS  PubMed  Google Scholar 

  7. Miller KB, Kim K, Morrison FS et al (1992) The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. Ann Hematol 65:162–168

    Article  CAS  PubMed  Google Scholar 

  8. Silverman LR, Demakos EP, Peterson BL et al (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J Clin Oncol 20:2429–2440

    Article  CAS  PubMed  Google Scholar 

  9. Silverman LR, Holland JF, Demakos EP et al (1994) Azacitidine (Aza C) in myelodysplastic syndromes (MDS), CALGB studies 8421 and 8921. Ann Hematol 68:A12

    Google Scholar 

  10. Silverman LR, Holland JF, Ellison RR (1990) Low dose continuous infusion azacytidine is an effective therapy for patients with myelodysplastic syndromes, a study of Cancer and Leukemia Group B. J Cancer Res Clin Oncol 116(suppl):816

    Google Scholar 

  11. Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10:223–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al (2010) Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 28:562–569

    Article  CAS  PubMed  Google Scholar 

  13. Nachtkamp K, Stark R, Strupp C et al (2016) Causes of death in 2877 patients with myelodysplastic syndromes. Ann Hematol 95:937–944

    Article  PubMed  Google Scholar 

  14. Mufti GJ, International Working Group on Morphology of myelodysplastic syndrome et al (2008) Diagnosis and classification of myelodysplastic syndrome: international Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica 93:1712–1717

    Article  PubMed  Google Scholar 

  15. Cheson BD, Greenberg PL, Bennett JM et al (2006) Clinical application and proposal for modification of the international Working Group (IWG) response criteria in myelodysplasia. Blood 108:419–425

    Article  CAS  PubMed  Google Scholar 

  16. Greenberg P, Cox C, LeBeau MM et al (1997) International scoring system for prognosis in myelodysplastic syndromes. Blood 89:2079

    CAS  PubMed  Google Scholar 

  17. De Pauw B, Walsh T, Donnely et al (2009) 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 46:1813–1821

    Article  Google Scholar 

  18. Della Porta MG, Malcoavti L, Strupp C et al (2011) Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica 96:441–449

    Article  PubMed  Google Scholar 

  19. Merkel D, Filanovsky K, Gafter-Gvili A et al (2013) Predicting infections in high-risk patients with myelodyslastic syndrome/acute myeloid leukemia treated with azacitidine: a retrospective multicenter study. Am J Hematol 88:130–134

    Article  CAS  PubMed  Google Scholar 

  20. Ofran Y, Filanovsky K, Gafter-Gvili A et al (2015) Higher infection rate after 7-compared with 5- day cycle of Azacitidine in patients with higher-risk myelodysplastic syndrome. Clin Lymphoma Myeloma Leuk 15:e95–e99

    Article  PubMed  Google Scholar 

  21. Pomares H, Arnan M, Sánchez-Ortega I et al (2016) Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering fungal prophylaxis? Mycoses 59:516–519

    Article  CAS  PubMed  Google Scholar 

  22. Knipp S, Hildebrand B, Kündgen A et al (2007) Intensive chemotherapy is not recommended for patients aged > 60 years who have myelodysplastic syndromes or acute myeloid leukemia with high-risk karyotypes. Cancer 110:345–352

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Anna Schuck.

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Conflict of interest

Anna Schuck: Financial travel support from Celgene.

Judith Neukirchen: Financial travel support and speakers honorarium from Celgene.

Andrea Kündgen: Financial travel support from Celgene.

Thomas Schroeder: Financial travel support, research funding, lecture fees from Celegene.

Guido Kobbe: Research funding, financial travel support and lecture fees from Celgene.

Ullrich Germing: Speakers honorarium from Celgene, Janssen-Cilag, Novartis, Research support Celgene, Novartis.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Schuck, A., Goette, MC., Neukirchen, J. et al. A retrospective study evaluating the impact of infectious complications during azacitidine treatment. Ann Hematol 96, 1097–1104 (2017). https://doi.org/10.1007/s00277-017-3001-2

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  • DOI: https://doi.org/10.1007/s00277-017-3001-2

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