S4742 Bosutinib-Induced Moderate Pancolitis in a Patient With Chronic Myeloid Leukemia: A Rare Adverse Effect of a Second Generation Tyrosine Kinase Inhibitor

Introduction: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder driven by the BCR-ABL1 fusion gene. Tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes, with second-generation agents like Bosutinib used for patients intolerant or resistant to first-line therapy. While gastrointestinal side effects such as diarrhea are common, biopsy-proven colitis remains an underrecognized complication. Case Description/Methods: A 59-year-old man with CML, intolerant to multiple TKIs, began Bosutinib 400 mg daily. Over 6 months, he developed persistent watery and occasionally bloody diarrhea (3–4 episodes/day, including nocturnal), rectal burning, and a 40-pound weight loss. Dietary interventions and antidiarrheals were ineffective. Colonoscopy showed moderate pancolitis; biopsy revealed active colitis throughout the colon. Laboratory studies were unremarkable. After multidisciplinary evaluation, bosutinib was held, and the patient was treated with a 10-week course of prednisone resulting in significant symptom resolution. Due to limited alternatives, bosutinib was cautiously restarted at a lower dose with close monitoring. Discussion: Bosutinib-induced diarrhea is common, but histologically confirmed colitis is rare. Its pathophysiology is thought to involve inhibition of SRC family kinases important for epithelial signaling, barrier function, and immune homeostasis, resulting in mucosal injury and inflammation. Histologically, TKI-induced colitis features cryptitis, basal plasmacytosis, and increased apoptosis, resembling inflammatory bowel disease. Dysregulated cytokines (e.g., TNF-α, IL-1β) and alterations in gut microbiota may further contribute. In this case, endoscopic and histologic evaluation were key to ruling out other etiologies. Prednisone was effective, consistent with prior reports, and a reduced-dose rechallenge was successfully implemented, reflecting a practical approach in TKI-intolerant CML patients. Bosutinib-induced colitis is an uncommon but clinically important adverse effect. Physicians should consider this diagnosis in patients with persistent gastrointestinal symptoms during TKI therapy. Prompt endoscopic evaluation and histologic confirmation are essential for diagnosis. Management includes drug discontinuation and corticosteroids, with dose reduction and rechallenge as feasible options in select cases.