Inflammatory Response Following Neutrophil Recovery Postchemotherapy in Acute Myeloid Leukemia Cases Without Evidence of Infection: Role of Homing of Neutrophils

Neutropenic sepsis is a common clinical entity occurring in postchemotherapy patients. Infection may not be the cause of fever in such patients after neutrophil-count recovery. Herein, we present two patients who developed fever during the neutropenic phase of induction chemotherapy and were treated with broad-spectrum antibiotics until they were no longer febrile and had recovered their neutrophil count. Being off antibiotics, they redeveloped fever within 48-72 hours. These fevers seemed to be secondary to postinfectious inflammatory response and not infection, supported by the fact that adequate antibiotic treatment was given and the collected fluid contained neutrophils but the cultures were negative. We hypothesize an explanation for this phenomenon based on the "homing of neutrophils" to bone marrow, which involves chemoattraction of CXC chemokine receptor (CXCR)-4 expressed on neutrophils towards the chemokine stromal cell-derived factor (SDF)-1 (CXCL12) expressed constitutively by bone marrow. Literature has shown that elevation of SDF-1 levels at injured/inflamed sites might create a similar gradient. This gradient results in the migration of neutrophils to the sites of previous injury/inflammation, leading to the formation of sterile abscesses. Based on our cases, we also conclude that antibiotics do not prevent the formation or treat such sterile "abscesses"; however, the drainage of these "abscesses" and treatment with anti-inflammatory agents are useful in such cases.