Infectious Enterocolitis in Hematopoietic Cell Transplant with Post-Transplant Cyclophosphamide

Abstract

Despite the high incidence of diarrhea in hematopoietic cell transplant (HCT) and the frequent involvement of infections, evidence concerning patients receiving post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis in the molecular diagnostic era is limited. This study aimed to evaluate the characteristics, incidence, risk factors, and outcomes impact of infectious enterocolitis in patients with hematologic malignancies undergoing HCT from matched sibling, matched unrelated, and haploidentical donors using PTCy as GVHD prophylaxis. Retrospective analysis of infectious enterocolitis episodes in 399 patients undergoing HCT at a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity. Levofloxacin was used prophylactically until myeloid engraftment. Infectious enterocolitis episodes were diagnosed by both molecular-based techniques and stool cultures. Infectious enterocolitis affected 21% of patients, with 19% having more than one episode. The median onset and duration was of 83 and 13 days, respectively, 20% were nosocomial and 58% were managed ambulatorily. The 1-year cumulative incidence was 19%, with 39% occurring beyond day 100, and was similar for Clostridioides difficile infection (CDI; 7%), non-CDI bacterial (8%), and viral enterocolitis (6%), with no differences in clinical features. However, toxin-positive CDI lasted longer (22 days) than toxin-negative cases (10 days, P = .03) Bone marrow HCT significantly increased the risk of overall infectious enterocolitis, while moderate-severe chronic GVHD increased all-cause and viral enterocolitis incidence. Infectious enterocolitis did not significantly impact overall survival, GVHD disease-free relapse-free survival, and non-relapse mortality. Approximately one-fifth of PTCy-based HCT recipients develop infectious enterocolitis in the first year, typically resolving within 2 weeks, with higher incidence in bone marrow recipients and those with moderate-severe chronic GVHD. CDI, non-CDI bacterial, and viral infections had similar incidences and clinical features. While infectious enterocolitis does not significantly impact transplant outcomes, its diagnosis remains challenging.

Keywords: Clostridioides difficile; Infectious enterocolitis; Mycophenolate mofetil; Post-transplant cyclophosphamide; Sirolimus.