Neutropenic Enterocolitis in Adult Patients with Acute Leukemia: A Single Center Experience

Neutropenic enterocolitis (NEC), a complication associated with chemotherapy induced neutropenia, is defined by abdominal pain and fever with bowel wall thickening observed on imaging studies. The published literature regarding this complication comes from case reports and small, predominantly pediatric, series. We conducted a single center retrospective chart review to examine the clinical features of NEC in adults treated with chemotherapy for acute leukemia or myelodysplastic syndrome (MDS).

A key word search of radiology records for “acute leukemia” and “neutropenic enterocolitis” or “typhilitis” identified a total of 20 cases which occurred during the period of 1/2008 to 3/2012. Only cases with documented fever (T >38°C), abdominal pain, neutropenia (<500/mm³), and findings of submucosal edema, pericolonic inflammation or bowel wall thickening on computed tomographic imaging plus a diagnosis of acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) or high risk MDS were included. All 20 cases identified by the record search met these criteria.

Male: female ratio was 1:1 and the mean age was 51.5 years (range 25 to 82). There were 15 patients (pts) with AML, 3 with ALL, 1 with acute promyelocytic leukemia (APL) and 1 with high risk MDS. 10 pts developed NEC during hospitalization for newly diagnosed disease, 8 during relapsed disease, and 2 during remission consolidation therapy. 17 pts received anthracycline-based therapy prior to the development of NEC; 16 received cytarabine, of which 5 received high dose cytarabine. 13 pts had diarrhea. 5 pts had documented Clostridium difficile infection during the same admission. 11 pts had positive blood cultures during the course of NEC: Enterococcus faecium (6), E. coli (4), and Klebsiella species (1). All pts received broad spectrum antibiotics. 11 pts received a carbapenem antibiotic, 5 pts received an aminoglycoside antibiotic, 18 received anaerobic coverage, and 19 received antifungal coverage. 9 pts were placed on total bowel rest, 11 kept on a clear liquid diet, 13 received a proton pump inhibitor (PPI), 1 received an H2 blocker, and 13 received filgrastim to facilitate recovery of the neutrophil count. 3 pts died; the cause of death was attributed to NEC in all 3. The mean duration of time from the onset of symptoms to the time of documentation of NEC by means of imaging studies was 5.6 days (range 0–15), the mean overall duration of symptoms was 16.4 days (range 0–46), and the mean duration of neutropenia prior to the diagnosis of NEC was 10.9 days (range 0–32). The 3 pts who died had a shorter mean duration of time from the onset of symptoms to the time of documentation of NEC by imaging studies (1.7 days), shorter mean duration of symptoms (7.3 days), and shorter mean duration of neutropenia prior to diagnosis of NEC (6 days). Among the 17 pts who recovered from NEC these durations were 6.3 days, 17.9 days, and 11.7 days, respectively. The mean age of the 3 pts who died was 72 years (range 67–82); while the mean age of the 17 pts who recovered was 47 years (range 25–69). All 3 pts who died had AML, 2 receiving induction therapy and 1 remission consolidation therapy at the time of NEC. All 3 pts had involvement of the cecum on imaging. 1 had associated Clostridium difficile infection and 2 pts had positive blood cultures: Klebsiella species (1), Enterococcus faecium (1). 2 of the 3 pts who died had received a PPI and filgrastim. None of the 20 pts required surgical intervention.

NEC is a life threatening complication of treatment of acute leukemia and high risk MDS. This is the largest single institution retrospective case study of NEC developing in adult patients with acute leukemia. 17 of 20 pts recovered. The 3 pts who died as a result of NEC had a shorter duration of symptoms and neutropenia prior to the diagnosis of NEC, suggesting an aggressive form of the disease with rapid development of symptoms. Older age may be a risk factor for poor outcome. 11 of the 17 pts who survived were kept on a clear liquid diet, suggesting that complete bowel rest may not be necessary for the successful treatment of NEC. NEC remains a dreaded complication of acute leukemia therapy and further studies in the adult population are needed to establish guidelines for the diagnosis and optimal management of NEC.

No relevant conflicts of interest to declare.