Publication Only: Chronic lymphocytic leukemia and related disorders - Clinical
Infections represent a major contributor to morbidity and mortality in chronic lymphocytic leukaemia (CLL). Hypogammaglobulinemia (HGG) is a common immune dysfunction in CLL and has been associated with an increased risk of infections.
To analyze impact of HGG on infection free survival (IFS), infectious risk and major infections in a monocentric real life cohort of CLL patients followed for 25 years; to determine impact of IgA deficiency, combined antibody deficiency (CAD) and HGG late onset on infectious death risk.
We retrospectively evaluated 211 unselected CLL patients, diagnosed from 01/1988 to 03/2018, median age 64 years (range 37-88). HGG was evaluated at diagnosis (n = 175), before first line therapy (n = 100) and 12 months after therapy (n = 92). Infection rate during course of disease and infectious morbidity have been collected.
During the course of disease 126 patients (60%) underwent at least one infectious event, regardless of severity. Of these, 51 (24%) reported at least one major infectious event (grade ≥3 CTCAE), mainly pneumonitis, skin and soft tissue infections. IgA levels at diagnosis were significantly lower in B and C Binet stage (p = 0.002); IgG (p < 0.001) and IgA levels (p = 0.03) were significantly reduced in patients who experienced infections within 12 months after diagnosis (Fig.1-A); 51 patients (24%) reported major infections and showed reduced IgG and IgA levels at diagnosis (p = 0.01 and p = 0.006, respectively). 25-year IFS for major infections was 67.2% for the entire cohort. Patients in C Binet stage showed significantly lower IFS in comparison with A and B stage (21.5% vs 73.5% and 73.3%, respectively. P < 0.001) (Fig.1-B). In multivariate analysis IGHV unmutated status was associated with lower IFS (p = 0.009). CAD was observed ad diagnosis in 60% of patients with severe infections versus 27% of patients who did not experience these events (p < 0.001). Furthermore, 20.4% of patients developed a late onset CAD with a significant reduction of IFS and an increase of serious infectious events. Overall survival (OS) was heavily reduced by early infectious events occurred during the first year from diagnosis, with higher mortality rate in patients with CAD at diagnosis or late onset; in both cases, risk of infectious death was 10 times higher compared to remaining cohort (p = 0.004).
Our results confirmed the negative impact of HGG on infectious risk and major infections. IgA deficit and CAD were strong predictors for development of these events. Early identification of clinical profile of high risk infections (selective IgA deficit, CAD, late onset HGG) is useful in optimal management of CLL patients.