Grant: Project Grant - Priority Announcement - Cancer Survivorship

Infection is a leading cause of complications and death in patients undergoing hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy. C. difficile infection (CDI) occurs in up to one in every five HCT and CAR-T patients around the time of treatment and is associated with prolonged length of hospitalization, increased complications, and potentially reduced survival. From early studies, oral vancomycin appears effective at preventing CDI. However, most patients (nine in every ten) are unlikely to benefit from oral vancomycin prophylaxis. The presence of C.difficile (colonization) in the stool, prior to initiation of HCT/CAR-T treatment, can identify the majority of patients who will go on to develop CDI. This baseline stool screening offers a way to implement CDI prevention in only the highest risk patients and would be a new method that has never been studied. In addition, recent work evaluating blood markers of intestinal bacteria (the gut microbiome) suggest that these tests could be used to further enhance identification of patients at risk for CDI and may help predict those who could benefit from prophylaxis. We propose a Canadian randomized trial of oral vancomycin prophylaxis in high-risk C.difficile colonized patients to prevent occurrence of CDI among HCT and CAR-T patients. Embedded within this trial we will also evaluate blood microbial markers of CDI risk. This pilot study will be performed at 5 large Canadian hospitals that perform HCT and CAR-T therapy, over a 2 year period, with a planned enrolment of up to 200 participants. This study will inform the feasibility of a future and larger Canadian trial. The results of this pilot and future trial stand to change the standard of practice in HCT and CAR-T therapy in Canada and globally.