کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5526170 1547046 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ResearchCytomegalovirus reactivation in patients with refractory checkpoint inhibitor-induced colitis
ترجمه فارسی عنوان
واکنش اولیه سیتومگالوویروس در بیماران مبتلا به کولیت ناشی از مهارکننده بازرسی مقاوم در برابر جراحی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی


- Checkpoint inhibitors can cause immune-related colitis (irColitis).
- IrColitis can be refractory to immunosuppressive and immunomodulatory therapies.
- Refractory irColitis is often caused by reactivation of cytomegalovirus (CMV).
- CMV colitis can resolve after the application of ganciclovir.
- Different repetitive diagnostic measures are needed to detect CMV colitis.

ObjectivesImmune checkpoint inhibitors can cause severe immune-related adverse events, with immune-related diarrhea and colitis (irColitis) being among the most frequent ones. While the majority of patients with irColitis respond well to corticosteroid treatment ± other immunomodulatory drugs such as infliximab, some patients do not show resolution of their symptoms. In the present study, we analysed the frequency of therapy-refractory irColitis, the underlying cause, and useful diagnostic approaches.MethodsBetween 2006 and 2016, 370 patients with metastatic malignant melanoma were treated with checkpoint inhibitors at the Department of Dermatology at the University Hospital Essen. All patients were identified for whom diarrhea and/or colitis was documented in the digital patient records. Patients who did not respond to standard immunosuppressive therapy within 2 weeks were classified as refractory. Demographic and clinical data of all patients were collected.ResultsWe identified 41 patients with irColitis, the majority occurring during treatment with ipilimumab. Amongst these, 5 (12.2%) were refractory to standard immunomodulatory treatment with corticosteroids and infliximab. Therapy-refractory cases tended to show more severe inflammation in colonic biopsies (p = 0.04). In all therapy-refractory cases cytomegalovirus (CMV) was detectable. CMV-DNA in colonic biopsies and in plasma was significantly more often detectable in therapy-refractory cases (in colonic biopsies p = 0.005, in plasma: p = 0.002). Presence of serum CMV IgM and positive immunohistochemical stainings of colon biopsies for CMV were also associated with refractory colitis (p=0.021; p = 0.053).ConclusionsThis report on CMV reactivation during management of checkpoint inhibitor-induced colitis emphasises the need for repetitive diagnostic measures in treatment-refractory irColitis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 86, November 2017, Pages 248-256
نویسندگان
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