Infections in chronic lymphocytic leukemia. Analysis of incidence as a function of length of follow-up

Abstract

Background and methods: Infections represent the major cause of death in chronic lymphocytic leukemia (CLL); however, clinical studies dealing with their incidence have yielded inconclusive results. In order to address this issue we reviewed the records of 125 CLL patients (mean age 65.6 yrs; 81 M/44 F; Stage A, 48; Stage B, 37; Stage C, 40) followed up at our institution over a 10-year period.

Results: The 125 patients accrued 447 person-years, a mean of 3.8 years per person. There were 199 recorded infections: 47 severe (crude rate 9.8 per 100 person-years) and 72 moderate, respectively. The 5-year risk of developing a severe infection for the whole series was 26% (95% CI: 24.7-27.3%), and 21 out of 71 deaths (29.5%) could be attributed to infectious causes. Despite a linear trend toward increased risk (r = 0.98), hazard function analysis showed a constant pattern of risk (r = 0.30), suggesting a lack of correlation of this event with time. Furthermore, the 5-year risk of developing a severe infection increased to 57.1% (95% CI: 36.4-77.8%) for patients with low IgG levels (less than 6.5 gr/L), and to 68% for those with both low IgG levels and disease stage C. On the other hand, patients who experienced a severe infection more frequently had advanced clinical stage (P < 0.001), low IgG levels (P < 0.01) and diffuse bone marrow (BM) histology (P < 0.05).

Conclusions: Infection is a constant risk in CLL that is associated with shortened survival. Factors such as hypogammaglobulinemia and advanced disease appear to be the major predisposing factors.