Similar incidence of typhlitis in patients receiving various doses of daunorubicin or idarubicin as induction for acute myeloid leukemia.

BACKGROUND: The current standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed by abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction chemotherapy with idarubicin 12 mg/m2 (IDA), daunorubicin 60 mg/m2 (DNA60), or daunorubicin 90 mg/m2 (DNA90).

METHODS: Adult patients with AML or MDS receiving either daunorubicin or idarubicin along with cytarabine as part of their induction regimen between January 1, 2009 and June 30, 2013 were included. A definition of typhlitis required CT confirmation of inflammation of the cecum only, defined as non-tumoral bowel wall thickening with or without pericolonic fat infiltration and fluid, according to CTCAE version 4.03 along with clinical symptoms. The primary endpoint was to determine the incidence of typhlitis among IDA, DNA60, and DNA90. Secondary endpoints included characterizing the variability of doses used in induction therapy and identifying any potential risk factors for the development of typhlitis.

RESULTS: The overall incidence of typhlitis was 2.5%. When the definition was broadened to include the colitis, enteritis, or enterocolitis, the incidence increased. The inter-reliability ratings of the 2 radiologists' evaluations for each definition indicated substantial agreement (0.803 cecum, 0.834 ileocecal region only, and 0.752 enterocolitis). Neither the anthracycline chosen, nor the dose had a statistically significant impact on the incidence of typhlitis. In patients that developed typhlitis, all patients had clinical symptoms in addition to documented cecum inflammation on CT scan. All patients were managed conservatively with intravenous broad-spectrum antibiotics.

CONCLUSION: To our knowledge, this is the first study to compare the incidence of typhlitis in adult patients receiving idarubicin or daunorubicin for the treatment of AML. The cumulative incidence of typhlitis was similar to the currently published literature, with the incidence being similar irrespective of the anthracycline chosen or dose. All patients were managed conservatively with broad-spectrum antibiotics. A more definitive definition of typhlitis may help clinicians identify affected patients sooner and choose appropriate targeted therapy.