Monitoring of Innate Cellular Immune Response in Chronic Lymphocytic Leukemia- A Pilot Study to Assess Patient Risk of Infection
Dimitrios Kontoyiannis, M.D.
University of Texas M. D. Anderson Cancer Center
Abstract:
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Infections are a major cause of illness and death in patients with CLL. These patients are predisposed to infectious complications due to immune compromise inherent to the leukemia itself. In addition, chemotherapy, corticosteroids and/or monoclonal antibodies that are commonly used as treatment of CLL further predispose these patients to severe, often fatal infections. Despite advances in supportive care and the widespread use of antibacterial and antiviral prophylaxis, infection still accounts for over 60% of deaths in patients with CLL. Low levels of natural antibodies that fight infections in the serum (immunoglobulins) and low numbers of some important immune cells (e.g., white cell count) have long been considered to be major predisposing factors for severe, life-threatening infections in this patient population. However, persistent qualitative deficiencies in cellular immune function might equally be as important, since these immune cells are the initial critical line of defense protecting patients from catastrophic infection from a broad spectrum of pathogens.
Currently available laboratory tests can detect only quantitative deficiencies in immune cells and immunoglobulins through blood tests. However, these tests do not provide information on qualitative defects of cellular immunity critical for identifying patients who are at high risk of for serious infectious despite near normal cell counts. This pilot study, first of its kind, attempts to characterize the qualitative immunodeficiency in CLL patients, and focuses on differences in their phagocytic killing against key bacterial pathogens and fungi that frequently lead to death in CLL patients. Our long-term goal is to use data from this study to develop unique diagnostic tools that will enable clinicians to effectively identify patients who are at the highest risk for catastrophic infection. These patients could then be treated more aggressively with antibacterial, antifungal and antiviral prophylaxis to prevent death from an undiagnosed infection.