Current Approach to the Management of Neutropenia

Abstract

Neutrophils have a critical role in host defense. Reduction in the absolute neutrophil count to below 1,000/μL is associated with increased susceptibility to infection. The pattern of infections depends on the severity and the duration of neutropenia and other associated defects in host defense mechanisms and exposure to antibiotics and other drugs, particularly corticosteroids and immunosuppressive agents. Breaks in the integrity of the skin or the gastrointestinal mucosal surfaces serve as the portals of entry for the majority of infecting organisms. Empiric antibiotic therapy and hospitalization are almost always required for the management of fever (temperature >38.2°C) in a neutropenic patient. A single antibiotic (e.g., ceftazidime or imipenem) or a combination of antibiotics with activity against both gram-positive and gram-negative organisms usually provides effective antimicrobial therapy. In low-risk patients, trials of out-patient therapy are ongoing. When febrile neutropenia does not respond to empiric broad-spectrum antibacterial therapy, fungal infections, particularly Candida and Aspergillus, should be considered, and antifungal therapy should be initiated. Recently, availability of the hematopoietic growth factors, particularly G-CSF and GM-CSF, have changed the approach to prevention and treatment of neutropenia. Randomized controlled studies have established that these growth factors accelerate hematopoietic recovery following chemotherapy and bone marrow transplantation. By shortening the duration of neutropenia, many of the heretofore inevitable problems with fever and infection can be avoided. The only major factor limiting the use of these agents is their cost. Despite the use of these growth factors, some patients will still experience slow hematopoietic recovery. For these patients, use of neutrophil transfusions, possibly from G-CSF-stimulated normal donors, may prove to be a useful adjunctive therapy.