Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment

Abstract

Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial, and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. In this review, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.

Keywords: Bacteremia; Chemotherapy; Infectious disease; Leukemia; Sepsis; Stem cell transplantation.

Figure 1

Risk factors for infections in patients with leukemia. The figure summarizes risk factors for infection in leukemia patients, which broadly could be divided into disease specific factors, patient related factors, and treatment related factors.

Figure 2

Risk factors for infections in patients with leukemia. The figure illustrate an algorithm for management of FN in leukemia patients, including prognostic, diagnostic and treatment decision work up. Abbreviations: ANC, absolute neutrophil count; C, Celcius; FiO₂, Fraction of inspired Oxygen; GCS, Glasgow coma scale; L, liter; MAP, Mean Arterial Pressure; MASCC, Multinational Association for Supportive Care in Cancer; PaO₂, Partial pressure of Oxygen; Pip/tazo, piperacillin/tazobactam; qSOFA, quick Sepsis Related Organ Failure Assessment; SOFA, Sequential Organ Failure Assessment.