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Infectious complications of chronic lymphocytic leukaemia: pathogenesis, spectrum of infection, preventive approaches

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Infectious complications continue to be a major cause of morbidity and mortality in patients with chronic lymphocytic leukaemia (CLL). The pathogenesis of infections in these patients is multifactorial, related to inherent immune defects and therapy-related immunosuppression. Hypogammaglobulinaemia is an important predisposing factor for infection in all patients. The use of the purine analogues such as fludarabine, and monoclonal antibodies such as rituximab and alemtuzumab, has introduced a new spectrum of infectious complications caused by pathogens such as Pneumocystis, Listeria, mycobacteria, herpesviruses Candida and Aspergillus, related to the cellular immune suppression induced by these agents. This review focusses on the pathogenesis and risk factors for infections in patients with CLL, the spectrum of infectious complications and preventive approaches to infection in these patients, using antimicrobial and immunoglobulin prophylaxis and vaccination strategies.

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Pathogenesis of infection in patients with chronic lymphocytic leukaemia

Patients with CLL are at risk for infection for a variety of aetiologies. These patients have inherent immune defects in humoral, as well as cell-mediated, immunity, which are related to the primary disease process. These defects include hypogammaglobulinaemia, abnormalities in T-cell subsets and defects in complement activity and neutrophil/monocyte function [1], [2]. In addition, specific immunodeficiencies related to therapies rendered to these patients result in additional immunosuppression.

Spectrum of infectious complications in patients with CLL

There has been an evolution in the spectrum of infections that are more commonplace in patients with CLL. For the most part, this has been related to the introduction of newer therapies that have their own unique impact on immune function, as the purine analogues and monoclonal antibodies. We discuss this spectrum as follows by type of therapy administered.

Antimicrobial prophylaxis

There are no standard guidelines for antimicrobial prophylaxis in CLL patients, and in general, most recommendations for these agents are derived from clinical trials and anecdotal reports. Herpesvirus infections, most of which were localised grade 1/2 infections, have been found to be more common in patients receiving single agent fludarabine, as compared to chlorambucil in a retrospective review [12]. Some advocate the use of antiviral prophylaxis in CLL patients with a low CD4 count and in

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