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. Here, 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.

Oral mycobiome identification in atopic dermatitis, leukemia, and HIV patients – a systematic review

“…IFI also represents a significative factor of morbidity and mortality for acute leukemia (AL) patients [24]. The increased risk of IFI in these patients relies on a combination of several factors related to the disease itself, the status of the patients' health and the treatment modality [25]. In general, AL is characterized by an abnormal proliferation and differentiation of bone marrow progenitor cells that originate the myeloid and lymphoid cell lineages [25].…”

“…The increased risk of IFI in these patients relies on a combination of several factors related to the disease itself, the status of the patients' health and the treatment modality [25]. In general, AL is characterized by an abnormal proliferation and differentiation of bone marrow progenitor cells that originate the myeloid and lymphoid cell lineages [25]. Acute myeloid leukemia (AML) leads to neutropenia and impaired granulocyte functions, and immature myeloid cells can inhibit T-cell specific antigen response [25].…”

“…In general, AL is characterized by an abnormal proliferation and differentiation of bone marrow progenitor cells that originate the myeloid and lymphoid cell lineages [25]. Acute myeloid leukemia (AML) leads to neutropenia and impaired granulocyte functions, and immature myeloid cells can inhibit T-cell specific antigen response [25]. On the other hand, acute lymphocytic leukemia (ALL) is characterized by the proliferation of poorly differentiated lymphoid cells [26].…”

“…On the other hand, acute lymphocytic leukemia (ALL) is characterized by the proliferation of poorly differentiated lymphoid cells [26]. Neutrophil-depletion is believed to be the main factor that predicts a higher risk of IFI in AML than in ALL, with exception of Pneumocystis carinii pneumonia that is more common in the latter [24,25,27]. Despite of these differences, AML and ALL treatments have high doses of cytotoxic drugs in common, which results in leukopenia [25].…”

“…Neutrophil-depletion is believed to be the main factor that predicts a higher risk of IFI in AML than in ALL, with exception of Pneumocystis carinii pneumonia that is more common in the latter [ 24 , 25 , 27 ]. Despite of these differences, AML and ALL treatments have high doses of cytotoxic drugs in common, which results in leukopenia [ 25 ]. In addition, radio- and chemotherapy injure the mucosal barrier and this creates a propitious entrance for opportunistic pathogens [ 25 ].…”