Antibody Deficiency Secondary to Chronic Lymphocytic Leukemia: Should Patients be Treated with Prophylactic Replacement Immunoglobulin?

Abstract

Hypogammaglobulinemia is a common finding in chronic lymphocytic leukemia (CLL). Its incidence increases with disease duration and stage such that it is present in up to 85 % of patients at some point in their disease course. It is therefore important to monitor patients for the development of an antibody deficiency. However, not all patients with antibody deficiency secondary to CLL are symptomatic with bacterial infections. In addition patients are susceptible to viral, fungal and opportunistic infections as a result of iatrogenic immunosuppression and through a variety of disease-related mechanisms, which affect cellular immunity and phagocytes. Published guidelines suggest that patients with a history of recurrent bacterial infections and a documented failure of antibody production should be treated with antibiotic prophylaxis in the first instance, with replacement immunoglobulin reserved for those who continue to suffer with significant bacterial infections. Here we present a review of the existing literature in order to provide a practical approach, based on best available evidence, to the investigation, monitoring and treatment of patients with antibody failure secondary to CLL; and we highlight areas in which further studies are needed.

A Canadian Perspective on the Use of Immunoglobulin Therapy to Reduce Infectious Complications in Chronic Lymphocytic Leukemia

“…Those infections have traditionally been classified as moderate (that is, requiring oral antibiotics and no hospitalization) or severe (that is, requiring parenteral antibiotics or hospitalization, or both). Before the advent of novel therapeutics, mortality rates of 25%-50% were found to be directly attributable to such infections 7,8 .…”

“…Infections in patients with cll are paradigmatically bacterial in origin and tend to occur in the respiratory tract; however, they can also affect the skin, gastrointestinal tract, and bloodstream 7 . Before the use of purine analogues, the most frequent bacterial infections included Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli 8 .…”

“…In addition, certain antineoplastic agents (for example, purine analogues, alkylating agents, alemtuzumab, and combination chemotherapy) can also increase the risk of select viral diseases (herpes simplex, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 8, for instance) 7,8 . Furthermore, novel therapies have recently changed the landscape of cll treatment.…”

Secondary antibody deficiency – causes and approach to diagnosis

“…Malignancies, especially lymphoproliferative disorders (chronic lymphocytic leukaemia (CLL) 9 and myeloma), are commonly associated with hypogammaglobulinaemia. This may be due to the malignancy itself or treatment of the condition.…”

Clinical profile associated with infections in patients with chronic lymphocytic leukemia. Protective role of immunoglobulin replacement therapy

“…[10][11][12] Attempts have been made to define the risk factors for infections in CLL in order to select patients who could benefit most from IgRT, even with a pre-emptive approach. Dhalla et al 1 suggested that immunization responses could be used to stratify infection risk and select patients for IgRT. Freeman et al 13 proposed that screening patients with CLL for IgG subclass deficiency could be a useful adjunct in stratifying the patients' risk for infection.…”