Critical Complication in Childhood Leukemia: Neutropenic Enterocolitis, Risk Factors, and Outcomes

Abstract

Objective: Neutropenic enterocolitis is characterized by inflammation of the cecum and distal ileum. The clinical triad consists of fever, abdominal pain, neutropenia, and imaging findings of colonic inflammation. Herein, we report the clinical characteristics, imaging findings and risk factors of typhlitis in pediatric patients with leukemia.

Methods: In this retrospective study, 72 pediatric patients who were followed up due to acute lymphoblastic or myeloblastic leukemia and diagnosed with typhlitis were evaluated between August 2019 and March 2023. Typhlitis was diagnosed based on the presence of neutropenia (absolute neutrophil count [ANC] <500/mm³ or an ANC expected to decrease to <500/mm³ within the next 48 h), at least one clinical symptom or sign, and confirmatory imaging showing cecum wall thickness >3 mm on ultrasonography. Patients' data regarding age, sex, chemotherapy regimens, clinical symptoms, port/catheter and peripheral blood cultures, imaging findings, comorbidities, length of hospital stay, management of typhlitis, and mortality rates were evaluated.

Results: Neutropenic enterocolitis was diagnosed in 72 children based on clinical and imaging features with an incidence of 36% (5 patients had recurrent episodes). Common manifestations included abdominal pain (81.8%), fever (48.1%), and diarrhea (42.9%). The most isolated organism in patients' port catheter and peripheral blood cultures was Klebsiella pneumonia. The most frequently affected bowel segments as seen on ultrasonograms were the cecum and terminal ileum (37.7%). The mean wall thickness was 4.6±1.7 mm. The median duration of intravenous broad-spectrum antibiotic treatment in our patients was 13 days (range: 8 to 24). The mean time to resume chemotherapy in our patients was 13.6±15.5 days. The median hospital stay of patients due to neutropenic enterocolitis was prolonged by 12 days. Surgical intervention was performed in three patients due to intestinal perforation. Four patients (5%) died due to neutropenic enterocolitis and sepsis. Patients who died from typhlitis and sepsis had a longer duration of typhlitis, although this difference was not statistically significant in terms of mortality rates.

Conclusion: Neutropenic enterocolitis is a complex clinical challenge that requires early diagnosis and a multidisciplinary approach. It should be suspected in any patient who developed neutropenia because of chemotherapy and presents with gastrointestinal symptoms such as nausea, vomiting, diarrhea, and severe abdominal pain.

Keywords: children; leukemia; neutropenic enterocolitis.