Late Onset Colitis after Cord Blood Transplantation Is Consistent with Graft Versus Host Disease: Results of a Blinded Histopathological Review

Background: Cord colitis syndrome is a new proposed clinical entity characterized by late onset of watery diarrhea after umbilical cord blood transplantation (UCBT), with granulomatous inflammation and Paneth cell metaplasia, and response to antibiotics. Methods: We tested the hypothesis that recipients of UCBT at our institution had late occurring colitis distinct from colitis in other allograft recipients. We reviewed patients who had colon biopsies between days 70-365 after UCBT and marrow or peripheral blood allograft controls over a 5 years period. Archival histological material was reviewed by the pathologist who was blinded to any type of clinical information. For each patient, a minimum of 32 serial sections of colonic tissue were examined from different anatomical areas. For all patients included in the analysis, we reviewed immunosuppressive therapy treatments, anti-viral, antibacterial, anti-fungal and anti-parasite medications at the time of the colon biopsy. Results: Forty-five UCBT patients were matched with 45 allograft controls (Figure 1). The two groups were similar with respect to age, intensity of conditioning regimen, sex, and diagnosis. No differences were seen in use of anti-bacterial and anti-fungal treatments, however patients receiving UCBT were more likely to be receiving valacyclovir than the control group (p=0.003).There was a significantly higher incidence of aGVHD grade 3-4 in the UCBT cohort compared to the controls (p=0.01). Forty-three patients in the UCBT group and 42 in the control group had evaluable biopsy specimens. Watery diarrhea was the indication for endoscopic biopsy in 10 UCBT and 11 controls while in the remaining patients the indication to colon biopsy was either abdominal pain, or nausea or anorexia. Among the UCBT group, the median time of onset and duration of diarrhea was 96 days (IQR 85-105) and 10 days (IQR 7-15), respectively. In the control group the median time of onset of diarrhea was 88 days (IQR 84-105 days) while the median duration was 10 days (IQR 7-15). Similar to the control group, no UCBT recipient with watery diarrhea was treated with antibiotics and all responded to systemic corticosteroids. No histological differences were seen between UCBT and controls except for increased eosinophils in the UCBT group (p=0.04). Distorted mucosal architecture and apoptotic crypt cells were the most common histological features in both groups, while Paneth cell metaplasia and epithelioid granulomas were rare findings (Figure 1). Conclusions: In this study population, colitis developing after day 70 post transplant was diagnosed as acute GVHD based on histopathology independent of the source of donor hematopoietic cells.  We could not identify the presence of a cord colitis syndrome in our UCBT patients.  

Figure 1. Formation of study population

Figure 2. Histopathological results