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Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality.

A variety of tyrosine kinase inhibitors (TKIs) are currently approved for the treatment of solid tumors and hematological cancers. However, TKIs are often associated with gastrointestinal (GI) adverse effects (AEs), especially diarrhea. Therefore, in the present study, we aimed to describe the clinical features and outcomes of TKI-associated lower GI AEs.This was a retrospective single-center cohort study of patients with cancer treated with TKIs from March 2016 to September 2020 who experienced diarrhea without other identifiable causes. Basic and GI AE-related characteristics and outcomes were compared using χOf 2172 patients who received TKIs over the study period, we included 228 in the final analysis. Of these, 166 (72.8%) had hematological cancers. Besides diarrhea, GI symptoms included nausea (36.4%), vomiting (21.9%), abdominal pain (15.4%), and bleeding (3.1%). Symptoms were typically mild, with 209 patients (91.7%) presenting with Common Terminology Criteria for Adverse Events grade 1-2 diarrhea. Only 5 patients (2.2%) received immunosuppressants for diarrhea treatment, 83 (36.4%) received no treatment, 29 (12.7%) received antibiotics, 101 (44.3%) received supportive antidiarrheal medications, and 17 patients (7.5%) needed TKI dose reduction or cessation of TKI use. When compared with patients with hematological cancers, those with solid tumors had a higher rate of hospitalization (29.0% vs. 7.2%; p 0.001) and mortality (75.8% vs. 43.4%; p 0.001) but a lower rate of recurrence of GI AEs (21.0% vs. 42.8%; p = 0.003. Only 15 patients (6.6%) underwent colonoscopy, with normal endoscopic findings in 8 patients (53.3%) and nonulcerative inflammation in 5 patients (33.3%). The inflammation universally involved the left colon. Twelve of the 15 patients who underwent colonoscopy had active colitis. In the hematological cancer group, patients with acute myeloid leukemia had a lower GI AE recurrence rate than did patients with other hematological cancers (7.2% vs. 30.1%; p = 0.001).Ten percent of cancer patients receiving TKIs experienced lower GI AEs, which were usually mild. Symptoms TKI-related GI adverse effects were nonspecific, often overlapping those of other cancer therapy-related GI AEs. Treatment of GI AEs was largely supportive, with limited roles for antibiotics and immunosuppressants.

Background Yersinia enterocolitica is usually transmitted through ingesting or handling undercooked pork products and is an uncommon cause of diarrhea, mesenteric adenitis and bacteremia in the United States. There is limited information regarding its clinical course in immunosuppressed and cancer patients. We describe the clinical presentation and outcomes of cancer patients diagnosed with Y. enterocolitica at a Comprehensive Cancer Center in the United States before and after the use of nucleic acid amplification testing (NAAT) using GI multiplex panel (GIMP). Methods We studied all patients with Y. enterocolitica isolated from cultures or identified by NAATs. We then obtained demographic information, comorbidities, co-infections, clinical characteristics, treatment and overall mortality at 30 days post diagnosis. Results Sixteen cases were identified (Table 1). The most common symptom of Y. enterocolitica infection was diarrhea [10/16 (62%)], followed by abdominal pain [8/16 (50%)] and fever [4/16 (25%)]. Ten of the cases were identified by NAAT over a 2-year period, compared with six cases identified prior to April 2016 over 70 years. Stool cultures confirmed Y. enterocolitica infection in two cases identified by NAAT (20%). Three patients had co-infection with Clostridium difficile, and four patients had a history of C. difficile infection. All but one patient was treated, mostly with a fluoroquinolone. Thirty-day mortality was 7.7%. Cause of death was most often a complication of advanced cancer. The one patient who did not receive antibiotics had maxillary sinus squamous cell cancer and had spontaneous resolution of symptoms. Conclusion GIMP NAATs have increased the rates of Y. enterocolitica identification in patients with cancer, suggesting that this disease was underdiagnosed or is now more common as patients receive increasingly intensive immunosuppression. GIMP NAATs will likely re-define the epidemiology of Y. enterocolitica infection in cancer patients. In patients with Y. enterocolitica who are at high risk for C. difficile relapse and in whom no recent immunosuppression or evidence of systemic illness is present, it may be reasonable to consider observation or shorter course of antibiotics. Disclosures All authors: No reported disclosures.