Cord Colitis: An Antibiotic-Responsive Colitis Syndrome Following Cord Blood Stem Cell Transplantation
Authors: Soriano Gabriela , Herrera Alex F , Hornick Jason L , Gilmore Erin , Ho Vincent T , Ballen Karen K , Baden Lindsey R , Cutler Corey S , Antin Joseph H. , Soiffer Robert J , Marty Francisco M 
Published: October 2019

Abstract
Abstract 1270
After umbilical cord blood transplantation (CB-SCT), we have observed a new syndrome of culture-negative antibiotic-responsive diarrhea, with pathologic findings on biopsy suggestive of an infectious/inflammatory colitis, but distinct from graft-versus-host disease (GVHD). The clinical characteristics and epidemiology of this gastrointestinal syndrome have not been previously described.
We studied the entire CB-SCT cohort at our center from 3/2003 through 3/2010. Charts were reviewed in detail for all episodes of diarrheal illness after engraftment. Demographic, CB-SCT, and diarrheal illness characteristics, and gastrointestinal pathology were analyzed. Cord colitis syndrome (CCS) was defined as a persistent diarrheal illness in a CB-SCT recipient not due to GVHD, cytomegalovirus, Clostridium difficile or other identifiable etiology on extensive microbiologic and pathologic examination, with histopathological evidence of colitis, and who responded to empirical antibacterial treatment.
104 patients underwent CB-SCT during the study period; 101 were double cord recipients. 72 underwent reduced-intensity conditioning, most commonly with fludarabine, melphalan, and thymoglobulin; 32 underwent myeloablative conditioning with cyclophosphamide, fludarabine, total-body irradiation or other agents. GVHD prophylaxis with sirolimus and tacrolimus was used in 69 patients, cyclosporine and mycophenolate mofetil in 17, and other combinations in the rest of the cohort. Median follow up was 452 days (range, 1–2409).
Eleven (10.6%) patients met criteria for CCS; an additional patient had relapsing antibiotic-responsive diarrhea compatible with CCS, but was not biopsied and not included in the analysis. The 1-year cumulative probability of CCS was 0.159. Median time to onset of CCS was 131 days after CB-SCT (range, 88–314). Patients reported watery, non-bloody diarrhea, commonly associated with weight loss. 8 patients required hospital admission. 7 patients underwent abdominal imaging during their evaluation, 6 had colonic involvement (3 with pancolitis). All patients underwent colonoscopy a median of 18 days (range, 5–59) after the onset of CCS. On gross inspection, 9 had mucosal erythema and 7 had mucosal ulcerations. Pathologic review of the colorectal biopsy specimens revealed diffuse active colitis (6 cases) or chronic active colitis (5 cases); 7 of them demonstrated loose granuloma formation. No biopsies had evidence of active GVHD, pseudomembranous colitis, viral cytopathic changes, nor evidence of CMV or adenovirus on immunostains. 9 patients were treated with a fluoroquinolone and metronidazole, 2 others were treated with metronidazole alone. All patients responded to antibiotic treatment initially, but 4 relapsed, requiring further treatment courses. Patients were initially treated for a median of 14 days (range, 10–90 days) and relapsed patients were treated for a median of 120 days (range, 30–330).
There was no association between the occurrence of CCS and age, underlying disease, conditioning or GVHD prophylaxis agents used. There was no clustering of cases over time. CCS patients (5/11) were more likely to have a prior diagnosis of grade II or higher acute GVHD compared to the cohort (16/93; p=0.04), without organ-specific predominance. The median time from acute GVHD to CCS diagnosis was 184 days (range, 105–328). The crude mortality at the end of follow-up was lower among patients who developed CCS (27.3%) compared to the rest of the cohort (58.1%; Log-rank 0.04).

Conclusions:
CCS is a distinct diarrheal illness that affects CB-SCT recipients that is antibiotic-responsive and differs from other common causes of diarrhea following SCT. Histologic findings mimic idiopathic inflammatory bowel disease and often include granulomatous colitis. This entity should be considered in CB-SCT patients with diarrhea in which other common causes of diarrhea have been ruled out. Further investigation is underway to determine whether there is an infectious etiology responsible for this syndrome or if it is an inflammatory colitis of alloimmune or autoimmune origin.

Disclosures:
No relevant conflicts of interest to declare.