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Chronic lymphocytic leukemia

Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal nation-wide cohort study

A Correction to this article was published on 27 July 2020

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Abstract

Patients with chronic lymphocytic leukemia (CLL) have a high risk of bloodstream infections (BSI). BSI cause significant morbidity and mortality among CLL patients; approximately one-third of fatalities in CLL list infections as cause of death. All CLL patients in Denmark diagnosed between 2008 and 2016 were followed through registries for the event of a BSI. Patient characteristics and bacterial findings were analyzed separately for treatment-naive and treated patients. A total of 3677 and 1020 patients with CLL were followed as treatment-naive and treated patients, respectively. We identified 145 cases of Gram-positive bacteremia. Streptococcus pneumoniae accounted for 32 (22%) cases, while Staphylococcus aureus was found 30 times (21%). Gram-negative microorganisms were found in 166 (46%) cases. Escherichia coli accounted for 77 (46%) cases. Lastly, we identified six episodes of candidemia of which five (83%) were fatal within 30 days of the infection. Based on increased frequency of S. pneumoniae and Pseudomonas aeruginosa and the high mortality of candidemia in CLL, empirical antibiotics with double coverage for S. pneumoniae and P. aeruginosa is recommended; upon suspected or proven candidemia, treatment with broad-spectrum fungicidal agents are recommended.

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References

  1. da Cunha-Bang C, Geisler CH, Enggaard L, Poulsen CB, de Nully Brown P, Frederiksen H. The Danish National Chronic Lymphocytic Leukemia Registry. Clin Epidemiol. 2016;8:561–5.

    Article  Google Scholar 

  2. Cunha-Bang C, da, Simonsen J, Rostgaard K, Geisler CH, Hjalgrim H, Niemann C. Improved survival for patients with CLL in the era of combination chemoimmunotherapy - a Danish Population Based Study. Blood 3. 2015;126:1740.

    Article  Google Scholar 

  3. Francis S, Karanth M, Pratt G, Starczynski J, Hooper L, Fegan C. The effect of immunoglobulin VH gene mutation status and other prognostic factors on the incidence of major infections in patients with chronic lymphocytic leukemia. Cancer. 2006;107:1023–33.

    Article  CAS  Google Scholar 

  4. da Cunha-Bang C, Simonsen J, Rostgaard K, Geisler C, Hjalgrim H, Niemann CU. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: a Danish population-based study of 10455 patients. Blood Cancer J. 2016;6:e499–e499.

    Article  Google Scholar 

  5. Wadhwa P, Morrison V. Infectious complications of chronic lymphocytic leukemia. Semin Oncol. 2006;33:240–9.

    Article  CAS  Google Scholar 

  6. Andersen MA, Eriksen CT, Brieghel C, Biccler JL, da Cunha-Bang C.Helleberg M, Incidence and predictors of infection among patients prior to treatment of chronic lymphocytic leukemia: a Danish nationwide cohort study. Haematologia. 2018;haematol.2017.182006.

  7. Crassini KR, Zhang E, Balendran S, Freeman JA, Best OG, Forsyth CJ. Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia. Br J Haematol 1. 2018;181:97–101.

    Article  CAS  Google Scholar 

  8. Moreira J, Rabe KG, Cerhan JR, Kay NE, Wilson JW, Call TG. Infectious complications among individuals with clinical monoclonal B-cell lymphocytosis (MBL): a cohort study of newly diagnosed cases compared to controls. Leukemia. 2013;27:136–41.

    Article  CAS  Google Scholar 

  9. Morrison VA. Infectious complications in patients with chronic lymphocytic leukemia: pathogenesis, spectrum of infection, and approaches to prophylaxis. Clin Lymphoma Myeloma. 2009;9:365–70.

    Article  CAS  Google Scholar 

  10. Blanco J, Muriel-Bombín A, Sagredo V, Taboada F, Gandía F, Tamayo L. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care Lond Engl. 2008;12:R158.

    Article  Google Scholar 

  11. Kjellander C, Björkholm M, Källman O, Giske CG, Weibull CE, Löve TJ. Bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal single-center study. Ann Hematol. 2016;95:871–9.

    Article  Google Scholar 

  12. Williams AM, Baran AM, Meacham PJ, Feldman MM, Valencia HE, Newsom-Stewart C. Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies. Leuk Lymphoma. 2018;59:625-632.

  13. Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54:4851–63.

    Article  CAS  Google Scholar 

  14. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446–56.

    Article  CAS  Google Scholar 

  15. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;25:2745-276.

  16. Voldstedlund M, Haarh M, Mølbak K. The Danish Microbiology Database (MiBa) 2010 to 2013. Eur Surveill. 2014;19:20667.

    Article  Google Scholar 

  17. Gubbels, S, Nielsen, J, Voldstedlund, M, Kristensen, B, Schønheyder, H, Ellermann-Eriksen, S, et al. National Automated Surveillance of Hospital-Acquired Bacteremia in Denmark Using a Computer Algorithm. Infection Control & Hospital Epidemiology. 2017;38:559–566. https://doi.org/10.1017/ice.2017.1

  18. Statistics Denmark: STATBANK:  http://www.statbank.dk/statbank5a/default.asp?w=1920

  19. The Comprehensive R Archive Network: https://cran.r-project.org/

  20. Twomey JJ. Infections complicating multiple myeloma and chronic lymphocytic leukemia. Arch Intern Med. 1973;132:562–5.

    Article  CAS  Google Scholar 

  21. Andersen MA, Vojdeman FJ, Andersen MK, Brown P de N, Geisler CH, Bjerrum OW. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death. Leuk Lymphoma. 2016;7:1–8.

  22. Freeman JA, Crassini KR, Best OG, Forsyth CJ, Mackinlay NJ, Han P. Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2013;54:99–104.

    Article  CAS  Google Scholar 

  23. Nørgaard M, Larsson H, Pedersen G, Schønheyder HC, Sørensen HT. Risk of bacteraemia and mortality in patients with haematological malignancies. Clin Microbiol Infect. 2006;12:217–23.

    Article  Google Scholar 

  24. Harboe ZB, Thomsen RW, Riis A, Valentiner-Branth P, Christensen JJ, Lambertsen L. Pneumococcal serotypes and mortality following invasive pneumococcal disease: A Population-Based Cohort Study. PLoS Med. 2009;6:e1000081.

    Article  Google Scholar 

  25. Backhaus E, Berg S, Andersson R, Ockborn G, Malmström P, Dahl M. Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors. BMC Infect Dis [Internet]. december 2016 [henvist 16. April 2018];16. Tilgængelig hos: http://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-1648-2

  26. Lindström V, Aittoniemi J, Salmenniemi U, Käyhty H, Huhtala H, Itälä-Remes M. Antibody persistence after pneumococcal conjugate vaccination in patients with chronic lymphocytic leukemia. Hum Vaccin Immunother. 2018;0:1–4.

    Google Scholar 

  27. Sinisalo M, Vilpo J, Itälä M, Väkeväinen M, Taurio J, Aittoniemi J. Antibody response to 7-valent conjugated pneumococcal vaccine in patients with chronic lymphocytic leukaemia. Vaccine. 2007;26:82–7.

    Article  CAS  Google Scholar 

  28. Svensson T, Kättström M, Hammarlund Y, Roth D, Andersson P-O, Svensson M. Pneumococcal conjugate vaccine triggers a better immune response than pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia A randomized study by the Swedish CLL group. Vaccine [Internet]. maj 2018 [henvist 22. maj 2018]; Tilgængelig hos: http://linkinghub.elsevier.com/retrieve/pii/S0264410X18306194

  29. Travade P, Dusart JD, Cavaroc M, Beytout J, Rey M. [Severe infections associated with chronic lymphoid leukemia. 159 infectious episodes in 60 patients]. Presse Med Paris Fr 1983. 1986;15:1715–8.

    CAS  Google Scholar 

  30. Wardill HR, Bowen JM. Chemotherapy-induced mucosal barrier dysfunction: an updated review on the role of intestinal tight junctions. Curr Opin Support Palliat Care. 2013;7:155–61.

    Article  Google Scholar 

  31. Yel L. Selective IgA deficiency. J Clin Immunol. 2010;30:10–6.

    Article  CAS  Google Scholar 

  32. Nørgaard M, Larsson H, Pedersen G, Schønheyder HC, Sørensen HT. Haematological malignancies–A predictor of a poor outcome in patients with bacteraemia. J Infect. 2006;53:190–8.

    Article  Google Scholar 

  33. Gubbels S, Nielsen J, Voldstedlund M, Kristensen B, Schønheyder HC, Vandenbroucke-Grauls CMJE, et al. Utilization of blood cultures in Danish hospitals: a population-based descriptive analysis. Clin Microbiol Infect. 2015;21:344.e13–e21. https://doi.org/10.1016/j.cmi.2014.11.018

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by Danish National Research Foundation grant 126 through the PERSIMUNE project. We thank the Danish hematology centers that participated with data submission to the Danish National CLL Registry. The following physicians contributed to data collection and represent the Danish Hematology centers participating in the Danish National CLL Registry: Christian Hartmann Geisler, Lisbeth Enggaard, Christian Bjørn Poulsen, Peter de Nully Brown, Henrik Frederiksen, Olav Jonas Bergmann, Elisa Jacobsen Pulczynski, Robert Schou Pedersen, and Linda Højberg Nielsen.

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Correspondence to Carsten Utoft Niemann.

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CUN has received consultancy fees and/or travel grants from Janssen, Abbvie, Novartis, Roche, Gilead, AstraZeneca, and CSL Behring, research support from Abbvie and Janssen, outside this project. This work is in part supported by funding from Novo Nordisk Foundation, grant NNF16OC0019302. The other authors declare that they have no conflict of interest.

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Andersen, M.A., Moser, C.E., Lundgren, J. et al. Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal nation-wide cohort study. Leukemia 33, 662–670 (2019). https://doi.org/10.1038/s41375-018-0316-5

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