Severe hemorrhagic colitis in a patient with chronic myeloid leukemia in the blastic phase after dasatinib use

Abstract

Dasatinib is a second-line tyrosine kinase inhibitor used in patients with imatinib resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute leukemia. Gastrointestinal bleeding may occur in up to 7% of patients using dasatinib, although, severe dasatinib-related acute colitis had rarely been reported. Here, we present the case of a 36-year-old female who progressed to acute myeloid leukemia after fourteen months of receiving imatinib for CML in the chronic phase and was treated with a dasatinib-containing chemotherapy regimen. On day 34 of treatment, the patient developed moderate abdominal pain and bloody diarrhea with mucous. Analyses of stool specimens were negative for parasites, Clostridium difficile, and other pathogenic bacteria. The cytomegalovirus pp65 antigen was negative in her blood leukocytes. A colonoscopy revealed acute colitis, and a mucosal biopsy showed nonspecific colitis. The patient was treated with broad-spectrum antibiotics, bowel rest and hydration, and dasatinib treatment was stopped. Her bloody diarrhea improved within 72 h. After confirming cytological remission, the patient received initial course of consolidation, and dasatinib treatment was reinstated. However, hemorrhagic colitis recurred. After discontinuing dasatinib, herhemorrhagic colitis drastically improved and did not recur following the administration of nilotinib. The characteristics of our patient suggest that dasatinib treatment can lead to hemorrhagic colitis, which typically resolves after discontinuation of the drug.

Keywords: Philadelphia chromosome, Chronic myeloid leukemia, Dasatinib, Colitis

Core tip: Dasatinib is a second-line tyrosine kinase inhibitor used in imatinib resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute leukemia patients. Dasatinib, which binds to the active and inactive conformation of the BCR-ABL oncoprotein, demonstrates greater potency than imatinib for wild-type and mutant BCR-ABL cases, with the exception of the T315I mutation. The most frequent adverse effects include myelosuppression, diarrhea, nausea and peripheral edema. Severe dasatinib-relatedacute colitis without thrombocytopenia, coagulation abnormalities or colonic ulcers has rarely been reported. Here, we report the case of an adult patient with Philadelphia chromosome positive CML in the blastic phase who developed acute colitis after dasatinib use.