Disease activity and pretreatment, rather than hypogammaglobulinaemia, are major risk factors for infectious complications in patients with chronic lymphocytic leukaemia

Abstract

To identify patients at high risk of life-threatening infections, we retrospectively analysed the prevalence of infectious complications in 187 chronic lymphocytic leukaemia patients treated in our institution since 1999 and correlated them with clinical features. A questionnaire with detailed questions regarding infectious complications was mailed to patients and their general practitioners. Major infections (requiring intravenous antibiotics or inpatient treatment) were reported in 37 patients (19.8%) and minor infections (requiring oral antibiotics and outpatient treatment) in 113 patients (60.4%). Univariate analysis identified advanced disease (P = 0.02), gender (P = 0.01), duration of disease (P = 0.007), number of previous chemotherapy regimens (P < 0.001), previous therapy with purine analogues and monoclonal antibodies (P < 0.001; P = 0.019), massive splenomegaly (P = 0.03), low granulocyte count (P < 0.001), low serum immunoglobulin concentration (P = 0.005), low haemoglobin concentration (P < 0.001) and high serum lactate dehydrogenase (LDH) concentration (P < 0.001) as risk factors for major infections. In multivariable logistic regression analysis, only the number of previous chemotherapy regimens (risk ratio [RR] = 1.8; 95% confidence interval [CI] 1.2-8.0) and haemoglobin concentration (RR = 0.6; CI 0.5-0.8) remained significant for major infections. The number of previous chemotherapy regimens was the only independent risk factor for minor (RR = 7.6; CI 2.2-25.7) and varicella-zoster virus infections (RR = 2.1; CI 1.3-3.4). In untreated patients, the only risk factor for major infections was LDH concentration. Patients treated with purine analogues or autologous stem cell transplantation had a higher risk of developing viral infections. In conclusion, disease activity and pretreatment extent have a stronger impact on the risk of severe infectious complications than hypogammaglobulinaemia. Preferably, prophylactic strategies should be evaluated in patients defined by these parameters.

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

“…Indeed, a great proportion of patients with unmutated IgV H genes require chemotherapy, which also may increase their risk of infections. 23,25 It is surprising that ZAP-70 expression was not predictive of infection risk, given the reported strong correlation between ZAP-70 expression and IgV H mutation status. 4 Our correlation was around 60%, clearly below most reported series, 4 implying that our ZAP-70 results must be regarded with caution.…”

“…7,10,23,25 Several predisposing factors have been suggested over the last 50 years, including hypo-g-globulinemia, neutropenia, defective T-cell function, and reduced complement activity. 7,26 In keeping with previous reports, the infective pattern observed in the current work was very similar to that observed in primary humoral immune deficiencies.…”

“…[23][24][25] The current study provides a comprehensive analysis of major infective complications in a large group of unselected patients with CLL. (D) genetic abnormalities, and (E) initial therapy.…”

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

“…A number of factors have been identified that contribute to increased risk of infection in patients with CLL, including age, type and/or number of prior treatments, and immune cell status [21,27,36]. A retrospective analysis of 187 patients with CLL demonstrated that the number of chemotherapy (p<0.001), purine analogue (p<0.001), and monoclonal antibody treatments (p=0.019) significantly increased the risk for major infections [21].…”

“…A retrospective analysis of 187 patients with CLL demonstrated that the number of chemotherapy (p<0.001), purine analogue (p<0.001), and monoclonal antibody treatments (p=0.019) significantly increased the risk for major infections [21]. Due to the chronic nature of CLL and subsequent disease relapses, most patients receive more than one treatment over the course of the malignancy.…”