TY - JOUR

T1 - Antimicrobial use before chronic lymphocytic leukemia

T2 - a retrospective cohort study

AU - Andersen, Michael Asger

AU - Rostgaard, Klaus

AU - Niemann, Carsten Utoft

AU - Hjalgrim, Henrik

N1 - Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2021

Y1 - 2021

N2 - Chronic lymphocytic leukemia (CLL) is accompanied by increased risk of potentially fatal infections. While this can mostly be attributed to disease-related immune dysfunction, it is not known if CLL patients are also constitutionally susceptible to infections. We linked nation-wide Danish registers to explore this possibility, approximating infection susceptibility by use of antimicrobials. We assessed the incidence of antimicrobials among CLL patients and matched controls from the general population for up to 22 years before index diagnosis, and among children and grandchildren of CLL patients and their matched controls. Our analyses showed that for CLL patients overall antimicrobial use began to increase gradually six years before leukemia diagnosis. Before this time point, CLL patients had used significantly more macrolides (relative risk = 1.15; 95% confidence interval 1.10–1.20), antimycotics (1.18; 1.08–1.30), and antivirals (1.62; 1.45–1.81) than controls for up to 22 years before diagnosis. The same pattern of increased use was found among CLL patients’ children and grandchildren. Our study suggests that CLL diagnosis is preceded by decades of increased susceptibility to infections. The duration of this time window is compatible with causal roles of immune dysfunction and/or certain infections in CLL pathogenesis, possibly mediating the association between constitutional infection susceptibility and CLL risk.

AB - Chronic lymphocytic leukemia (CLL) is accompanied by increased risk of potentially fatal infections. While this can mostly be attributed to disease-related immune dysfunction, it is not known if CLL patients are also constitutionally susceptible to infections. We linked nation-wide Danish registers to explore this possibility, approximating infection susceptibility by use of antimicrobials. We assessed the incidence of antimicrobials among CLL patients and matched controls from the general population for up to 22 years before index diagnosis, and among children and grandchildren of CLL patients and their matched controls. Our analyses showed that for CLL patients overall antimicrobial use began to increase gradually six years before leukemia diagnosis. Before this time point, CLL patients had used significantly more macrolides (relative risk = 1.15; 95% confidence interval 1.10–1.20), antimycotics (1.18; 1.08–1.30), and antivirals (1.62; 1.45–1.81) than controls for up to 22 years before diagnosis. The same pattern of increased use was found among CLL patients’ children and grandchildren. Our study suggests that CLL diagnosis is preceded by decades of increased susceptibility to infections. The duration of this time window is compatible with causal roles of immune dysfunction and/or certain infections in CLL pathogenesis, possibly mediating the association between constitutional infection susceptibility and CLL risk.

U2 - 10.1038/s41375-020-0980-0

DO - 10.1038/s41375-020-0980-0

M3 - Journal article

C2 - 32684631

AN - SCOPUS:85088146303

VL - 35

SP - 747

EP - 751

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 3

ER -