Dasatinib-induced colitis: clinical, endoscopic and histological findings

Abstract Background Dasatinib, a second-generation tyrosine kinase inhibitor, is widely used in patients with haematological malignancies. The main side effects of dasatinib are myelosuppression and pleural effusion; however, colitis, such as haemorrhagic colitis and cytomegalovirus (CMV) colitis, have been reported as rare side effects. There are only a few studies conducted on dasatinib-induced colitis. Aims This study aimed to clarify the clinical, endoscopic and pathological features of dasatinib-induced colitis. Methods This retrospective study included 51 consecutive patients who received dasatinib therapy between June 2009 and July 2020. Dasatinib-induced colitis was defined as the presence of colitis symptoms, exclusion of other diseases that could cause colitis, and improvement in symptoms after dasatinib withdrawal or dose reduction. CMV positivity was determined based on the positive result of CMV immunostaining. Results Dasatinib-induced colitis was diagnosed in nine of 51 patients (17.6%), and most of the symptoms were mild diarrhoea and bloody stools. The endoscopic findings were characterised by loss of vascular pattern (100%) and multiple small erosions (83.3%) which were mainly found in the transverse and descending colon. In a patient who underwent follow-up colonoscopy once a year while taking dasatinib, endoscopic findings changed from initial erythematous spots to multiple erosions, and finally to multiple small round elevations with erosion on the top that disappeared after discontinuation of dasatinib. Anti-CMV therapy was administered to one patient, but the treatment failed. All patients with dasatinib-induced colitis were cured after the discontinuation of dasatinib. Conclusion Physicians should consider CMV reactivation to manage dasatinib-induced colitis.

[1]  N. Ishimura,et al.  Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report , 2021, BMC Gastroenterology.

[2]  P. Katelaris,et al.  Dasatinib-induced colitis: a case report. , 2019, Pathology.

[3]  M. Plana,et al.  Immunomodulatory Activity of Tyrosine Kinase Inhibitors to Elicit Cytotoxicity Against Cancer and Viral Infection , 2019, Front. Pharmacol..

[4]  J. Hsu,et al.  Pancolitis associated with higher mortality risk of cytomegalovirus colitis in patients without inflammatory bowel disease , 2018, Therapeutics and clinical risk management.

[5]  Su Mi Choi,et al.  Cytomegalovirus Colitis during Dasatinib Treatment for Patients with Hematologic Malignancy: Case Series and Literature Review , 2018, Infection & chemotherapy.

[6]  Yeon-Geun Choi,et al.  Dasatinib induces severe hemorrhagic colitis in a patient with accelerated phase of chronic myelogenous leukemia , 2016, The Korean journal of internal medicine.

[7]  N. Kadowaki,et al.  Cytomegalovirus pulls strings behind NK cells , 2017, Oncotarget.

[8]  Hong Yang,et al.  The Association Between CMV Viremia or Endoscopic Features and Histopathological Characteristics of CMV Colitis in Patients with Underlying Ulcerative Colitis , 2017, Inflammatory bowel diseases.

[9]  Kotaro Suzuki,et al.  Clinical efficacy of fecal occult blood test and colonoscopy for dasatinib-induced hemorrhagic colitis in CML patients. , 2017, Blood.

[10]  T. Onaka,et al.  Principal component analysis uncovers cytomegalovirus-associated NK cell activation in Ph+ leukemia patients treated with dasatinib , 2017, Leukemia.

[11]  T. Onaka,et al.  Principal component analysis uncovers cytomegalovirus-associated NK cell activation in Ph+ leukemia patients treated with dasatinib , 2017, Leukemia.

[12]  I. Aldoss,et al.  Dasatinib-Induced Colitis after Allogeneic Stem Cell Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. , 2016, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[13]  M. Baccarani,et al.  Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  A. Soliman,et al.  Cytomegalovirus-induced Hemorrhagic Colitis in a Patient with Chronic Myeloid Leukemia (Chronic Phase) on Dasatinib as an Upfront Therapy , 2015, Clinical medicine insights. Case reports.

[15]  Govinda R Brahmanday,et al.  Dasatinib-induced haemorrhagic colitis in chronic myeloid leukaemia (CML) in blast crisis , 2013, BMJ Case Reports.

[16]  Y. Kanda,et al.  Investigation of the freely available easy-to-use software ‘EZR' for medical statistics , 2012, Bone Marrow Transplantation.

[17]  S. Mustjoki,et al.  Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy , 2008, Leukemia.

[18]  A. Jankowska,et al.  Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. , 2008, Blood.

[19]  F. Prósper,et al.  Parvovirus B19 acute infection and a reactivation of cytomegalovirus and herpesvirus 6 in a chronic myeloid leukemia patient during treatment with dasatinib (BMS-354825) , 2007, Leukemia & lymphoma.

[20]  T. Iwasaki ALIMENTARY TRACT LESIONS IN CYTOMEGALOVIRUS INFECTION , 1987, Acta pathologica japonica.