Significance of Fecal Occult Blood Test Followed By Colonoscopy for Asymptomatic Dasatinib-Induced Hemorrhagic Colitis (CML1501 Study)

Introduction: Positive fecal occult blood test (FOBT) was occasionally observed in some chronic myeloid leukemia (CML) patients treated with a tyrosine kinase inhibitor (TKI). Although there are several case reports of hemorrhagic colitis in patients treated with dasatinib, the incidence of TKI-induced hemorrhagic colitis and the screening efficacy of FOBT followed by colonoscopy are unknown.

Methods: We prospectively enrolled CML patients treated with a TKI. The first FOBT (FOBT1) was performed for all patients. The first CF (CF1) was performed for patients with positive FOBT1. When there were any lesions, tissue biopsy was performed for pathological analyses. After confirmation of TKI-induced colitis by pathological analyses, the TKI was interrupted for 2-4 weeks. And then, FOBTs were re-evaluated (FOBT2).

Results: Between February 2015 and September 2015, 30 patients were enrolled in this study. All patients were in chronic phase. FOBT1 was positive in 10 of 30 patients. All patients with positive FOBT1 were treated with dasatinib and revealed no symptoms. CF1 was performed for 10 patients with positive FOBT1. All patients showed abnormal endoscopic findings: colitis in 6 patients, polyps in 3, and hemorrhoid in 1. Dasatinib-induced hemorrhagic colitis was confirmed in 6 of 18 patients treated with dasatinib (33%). Median duration of dasatinib before FOBT1 was 16 months (range 3-35 months). Median dose of dasatinib was 85mg (range 50-100mg). It had been reduced in 3 patients due to pleural effusion. Its endoscopic feature was read flare and/or erosion. Immunohistological analyses showed CD3+, CD8+, CD56+ and Granzyme B+ cytotoxic T lymphocyte infiltration. Dasatinib was discontinued at a median of 27 days after CF1 in patents with dasatinib-induced hemorrhagic colitis. Discontinuation period was 14 days in 4 patients, 27 days in 1, and 28 days in 1. FOBT2 was negative in all but one patient who had concurrent colorectal polyps. No CML progression due to dasatinib discontinuation was observed.

Conclusion: Dasatinib-induced hemorrhagic colitis was observed in a third of asymptomatic patients treated with dasatinib. FOBT can be a useful non-invasive screening for the disease, and it can be confirmed by the following CF and pathological analyses. It was caused by cytotoxic T lymphocytes, and hemorrhage was resolved after dasatinib discontinuation.