A 67-year-old male patient presented with a three-day history of diarrhea. He had received 14 months of dasatinib therapy (100 mg/day) for the treatment of CML, and He had chronic kidney disease. Physical examination revealed no fever and mild abdominal pain without any tenderness. At hospitalization, he had white blood cell (WBC) count of 19,430/mm³ (lymphocyte, 71%), hemoglobin (Hb) level of 8.0 g/dl, platelet count of 239,000/mm³, and a blood urea nitrogen/creatinine ratio of 85.2/3.08 mg/dl. On the 2nd day, his WBC count declined sharply to 8,720/mm³ (lymphocyte 20%), and he developed hematochezia without thrombocytopenia on 3rd day of admission. At this point, his blood and stool cultures tested negative. Dasatinib-induced hemorrhagic colitis was suspected, and a total colonoscopy revealed edematous and friable mucosa, along with a loss of vascularity from the cecum to rectum (Fig. 1A). His symptoms did not improve upon the discontinuation of dasatinib and with conservative care. After 4 days of admission, biopsy tissue showed positive CMV-specific IHC staining, and a blood CMV real time quantitative polymerase chain reaction (RQ-PCR) also tested positive (760 copies/ml). His symptoms subsided following 19 days of ganciclovir (5 mg/kg IV q12hr) administration. Dasatinib was re-started subsequently, and the CMV colitis did not relapse (15 months).

A 43-year-old female patient complained of watery diarrhea and abdominal pain for two weeks. She had received two months of dasatinib (140 mg/day) for chronic phase CML and entecavir (0.5 mg/day) for chronic hepatitis B. Hematochezia and fever (38.1°C) developed on the day of admission. Her laboratory results were as follows: WBC count, 7,390/mm³ (lymphocyte, 34%); Hb, 8.4 g/dl; platelets, 141,000/mm³; and C-reactive protein, 2.7 mg/dl. Empirical antibiotic treatment (cefepime, metronidazole) was administered. However, the diarrhea and hematochezia persisted.

A sigmoidoscopy revealed multiple diffuse erythema, and shallow ulcerations with spontaneous bleeding involving the rectum and sigmoid colon (Fig. 1B). These findings indicated CMV colitis, dasatinib-induced hemorrhagic colitis, or both, and dasatinib was discontinued. On day 5, she showed decreased lymphocyte count (1,080/mm³), blood CMV load of 1,650 copies/ml, and positive CMV-specific IHC staining in the biopsied colon tissue (Fig. 2). CMV colitis was diagnosed and ganciclovir (5 mg/kg IV q12hr) was administered. Her dasatinib treatment was restarted during this time. After five days of ganciclovir treatment, she again developed hematochezia, and dasatinib was discontinued for a second time. A repeat sigmoidoscopy revealed improvements, and the CMV IHC staining and RQ-PCR both tested negative. However, a Clostridium difficile toxin assay tested positive. She was treated with metronidazole (1,500 mg/day PO) and vancomycin (500 mg/day PO). After 12 days of ganciclovir administration and antibiotic regimen for C. difficile-associated diarrhea (CDAD), she got better; dasatinib was restarted and she was discharged. The CMV colitis did not relapse (16 months).

A 51-year-old male patient visited our outpatient clinic for consultation on CMV colitis. He had undergone a colonoscopy two weeks before at a local clinic for a small amount of hematochezia, and had received a CMV colitis diagnosis. He had started receiving dasatinib (140 mg/day) for chronic phase CML 14 months prior to the onset of hematochezia, and had also received 6 cycle of systemic chemotherapy for diffuse large B-cell lymphoma nine months before symptom onset. Dasatinib had been maintained subsequent to the end of chemotherapy. At the time of presenting as an outpatient, the hematochezia had subsided and he had no symptoms.

His laboratory results revealed WBC of 6,330/mm³ (lymphocyte, 54%) without lymphopenia, Hb of 11.4 g/dl, and platelets of 199,000/mm³. Because, he was in stable condition and his laboratory results were within normal limits, dasatinib was maintained and CMV colitis treatment was not initiated. Six weeks after presentation, he re-developed hematochezia. A colonoscopy was performed again and the results revealed erythema, friability, and easy touch bleeding from the ileocecal valve to the sigmoid colon. Further, tissue biopsy also showed positive CMV-specific IHC staining. Thereafter, he received three weeks of oral valganciclovir (900 mg BID) treatment, and his symptoms improved. Hematochezia developed again two weeks after the end of the valganciclovir treatment. A repeat colonoscopy showed improvements, and his symptoms of hematochezia became better than before. We therefore decided to observe him without retreatment for CMV. The dasatinib dose was maintained, and CMV colitis did not relapse (16 months).

A 54-year-old male patient presented with diarrhea and hematochezia. He was treated with dasatinib (100 mg/day) for three months for relapsed Ph+ ALL, and had also received salvage chemotherapy of high-dose cytarabine, mitoxantrone, and etoposide. The laboratory results revealed persistent lymphopenia and thrombocytopenia (lymphocyte count, 748/mm³; platelets, 18,000/mm³). A sigmoidoscopy showed edematous mucosa with erythema and shallow erosions. Although CMV colitis was diagnosed based on the presence of pathologic tissue that showed positive CMV-specific IHC staining, symptoms continued to improve with conservative care and empirical antibiotic treatment (piperacillin, tazobactam) in the absence of any antiviral agent.

Hematochezia developed again ten days later. CMV colitis was confirmed based on pathologic findings in a repeat sigmoidoscopy (Fig. 1C), and blood CMV load of 925 copies/ml. In addition, a diagnosis of CDAD was made following positive toxin assay result and negative results for diarrheagenic bacterial pathogens (in-house multiplex PCR). Metronidazole and ganciclovir (5 mg/kg IV q12hr) were initiated, and while the diarrhea improved. After eleven days to initiation of ganciclovir, He once again developed hematochezia. Then, the dasatinib was discontinued. Symptom subsided completely after 18 days of ganciclovir treatment, CMV blood viral load was not detectable, CMV-specific IHC staining was negative from the third sigmoidoscopy. CMV colitis did not relapse in 9 months, at which time the patient succumbed to refractory leukemia.

A 55-year-old female patient with Ph+ ALL was admitted for double cord blood transplantation. She had been treated with dasatinib (140 mg/day) 5 month between induction and consolidation chemotherapy. The patient showed hematochezia and fever (38.3°C) at admission. Laboratory results on admission day revealed WBC count of 10,470/mm³ (lymphocyte, 31.3%), Hb of 7.9 g/dl, and platelets of 57,000/mm³. On day 2, her lymphocyte count dropped to 251/mm³, and she had a blood CMV load of 2,500 copies/ml. Sigmoidoscopy revealed mild erythematous mucosa with blood clot (Fig. 1D), and CMV-specific IHC stain. Ganciclovir was started for CMV colitis; her transplantation was delayed, and the dasatinib was maintained during this time. After ten days of ganciclovir treatment, the patient experienced neutropenia, a ganciclovir adverse effect. As the patient did not have any other symptoms more, and a repeat sigmoidoscopy revealed significant improvements, ganciclovir was discontinued and she was discharged. One week later, dasatinib was also discontinued due to poor response. The patient received double cord blood transplantation three months after discharge, and the CMV colitis relapsed one month after transplantation. She received retreatment with ganciclovir, showed improvements, and has not experienced a CMV colitis relapse 11 months after therapy conclusion.