Introduction

Since the earliest studies of chronic lymphocytic leukemia (CLL), it has been recognized that infectious complications are a major cause of morbidity and mortality. It is critically important that physicians caring for these patients have a thorough understanding of the host deficiencies predisposing to infection associated with the disease process and its therapy as well as the pathogens associated with these deficiencies. For example, introduction of the purine analogs has caused a major change in the infectious complications of these patients. Although this discussion focuses on the infectious problems in CLL, it should be recognized that many patients enjoy years of normal life, especially during the early stages of the disease.

Because of the chronicity of CLL and differing therapeutic approaches, precise information regarding the frequency of infectious complications over long periods of observation is difficult to obtain. Both the disease process itself and its therapy affect host defenses, and the types of infection depend on specific deficiencies in host defenses. Hence, there is a wide diversity of infectious complications in populations of CLL patients. It has been estimated that as many as 80% of these patients will develop at least one severe infection during the course of their disease, and approx 60% will die of infection (1). It has also been estimated that there is a mean of10 severe infectious episodes per 100 patient yr and that the 5-yr risk of developing a serious infection is about 25% (2). These latter figures are derived from a mixture of patients in various stages of the disease. Table 1 summarizes data on infectious complications from several studies.

Prior to the availability of effective therapy, most infections were attributed to deficiencies in immunoglobulins or occasionally to neutropenia secondary to bone marrow failure. Most of these infections involved the respiratory tract and were caused by encapsulated bacteria. In most reports Streptococcus pneumoniae was the predominant pathogen. The first effective therapeutic agents were alkylating agents, which were administered alone or in combination with vincristine and prednisone. Since alkylating agents are myelosuppressive, there was a shift to a predominance of Gram-negative bacillary infections associated with therapy-induced neutropenia. More recently, the discovery of the efficacy of the purine analogs, especially fludarabine, which have profound effects on cellular immunity, has led to a new spectrum of infections (see Subheading 2.3).

From: Contemporary Hematology Chronic Lymphocytic Leukemia: Molecular Genetics, Biology, Diagnosis, and Management Edited by: G. B. Faguet © Humana Press Inc., Totowa, NJ

Table 1

Frequency of Infection in Patients With Cancer

Table 1

Frequency of Infection in Patients With Cancer

Author

Yr

Patient

% Infected

% Died of infection

Osgood and Seaman (41)

1952

102

29

11

Shaw et al. (24)

I960

42

60

Aroesty and Furth (43)

1962

61

61

56

Zippin et al. (86)

1973

839

23

7

Revol et al. (87)

1974

266

39

Morrison et al. (50)

2001

Fludarabine

188

77

Chlorambucil

189

61

Combination

144

85

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