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

Abstract

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‐γ‐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 1 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)VH 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), IgVH mutation status (P < .001), and genetic abnormalities (P = .003) had a significant impact on infection‐related mortality.CONCLUSIONS.Clinical stage at diagnosis, IgVH 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. Cancer 2006. © 2006 American Cancer Society.

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

“…Recent studies have reported on the potential association between high-risk prognostic markers (e.g., elevated thymidine kinase, CD38 + status, unmutated IgV H status, and presence of genomic abnormalities) and an increased risk of developing infectious complications in patients with CLL [11,15]. The utility of these biomarkers in clinical practice remains to be established.…”

Perturbation of the normal immune system in patients with CLL

“…13, 40 In a study of 231 patients, those with U-CLL had increased infectious morbidity and mortality and shorter time to first infection compared with those with M-CLL. 40 Another study of untreated patients showed that U-CLL tumors were correlated with shorter time to onset of recurrent infection.…”

“…40 Another study of untreated patients showed that U-CLL tumors were correlated with shorter time to onset of recurrent infection. 13 However, U-CLL progress more rapidly, 3 and it remains difficult to exclude that the differences depend on different tumor load in the subsets.…”

Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time?

“…65,66 These percentages are probably higher in patients who are refractory to fludarabine and/or alemtuzumab, 15,29 precisely those patients who are referred for allo-HCT. This susceptibility is both disease and therapy-related and is secondary to multiple factors, including hypogammaglobulinemia, defective T and natural killer cell function, neutropenia, and deficient complement activity.…”