The effect of immunoglobulin VH gene mutation status and other prognostic factors on the incidence of major infections in patients with chronic lymphocytic leukemia

BACKGROUND. Infections are a major factor in the clinical course of chronic lymphocytic leukemia (CLL) and account for 30% to 50% of all deaths. The pathogenesis of infections in CLL is related to hypo-gamma-globulinemia, T-cell immune dysfunction, and the immunosuppressive effect of treatment. METHODS. The authors retrospectively assessed the correlations between new prognostic markers and types of infections encountered, the time taken to develop these infections, and infection-related mortality in 280 unselected patients with CLL. RESULTS. One hundred patients (36%) had at least I major infection (median, 2 major infections; range, 1-8 major infections) over a median follow-up of 67 months. Infections were the most common cause of death, accounting for 51% of all fatalities. Older age (P = .007), clinical Stage B or C disease (P <.001), unmutated immunoglobulin (Ig)V-H gene status (P <.001), genetic abnormalities (P <.001), positive CD38 status (P <.001), and type of initial therapy were associated with a significantly shorter time to first infection. Equally, patient age (P <.001), disease stage (P <.001), CD38 expression (P <.001), IgV(H) mutation status (P <.001), and genetic abnormalities (P = .003) had a significant impact on infection-related mortality. CONCLUSIONS. Clinical stage at diagnosis, IgV(H) mutation status, and initial therapy were possible predictors of severe infections in patients with CLL. The current results may help to identify which patients with CLL are at particularly high risk of developing serious infections and, thus, should be considered for Ig or antibiotic prophylaxis.