Colonic graft-vs.-host disease in autologous versus allogeneic transplant patients: earlier onset, more apoptosis, and lack of regulatory T-cell attenuation.

Histologic characterization of graft-vs.-host disease in autologous stem cell transplant patients has been limited. The aims of this study were to characterize colonic graft-vs.-host disease in autologous stem cell transplant patients and compare to a control group of allogeneic stem cell transplant patients, to determine whether graft-vs.-host disease can be diagnosed < 21 days post transplantation in autologous stem cell transplant recipients, and to quantify colonic T-cell populations in autologous stem cell transplant patients. Colonic biopsies taken to evaluate for graft-vs.-host disease in both allogenic and autologous stem cell transplant patients were reviewed for the maximum number of apoptotic bodies per 10 contiguous crypts. Immunohistochemical stains for CD4, CD8, and FoxP3 were performed. Clinical information was collected from chart review. The study group consisted of 122 colonic biopsies from 84 patients. Sixteen patients underwent autologous stem cell transplant and 68 allogeneic stem cell transplant. Autologous stem cell transplant patients underwent biopsy significantly earlier compared with allogeneic stem cell transplant patients (median 20 vs. 87 days, p = 0.0002), had significantly higher apoptotic counts compared with matched-related donor patients (7.5 vs. 3.9, p = 0.03), and had higher FoxP3-positive lamina propria lymphocytes counts compared to allogeneic stem cell transplant patients (9.2 vs. 5.3, p = 0.03). In patients undergoing biopsy < 21 days post transplantation, allogeneic stem cell transplant patients showed less CD8-positive lamina propria lymphocytes and a trend of less FoxP3- and CD4-positive lamina propria lymphocytes compared with autologous stem cell transplant patients. Autologous stem cell transplant patients have more prominent crypt apoptosis compared with allogenic stem cell transplant patients and do not have numerically decreased FoxP3-positive lamina propria lymphocytes. Presence of robust T-cell populations in the early period following transplantation suggest that the 21-day cutoff for diagnosis of graft-vs.-host disease is not applicable to autologous stem cell transplant patients.

Diagnostic phrasing is independently correlated with the decision to treat for graft-versus-host disease: retrospective review of colon biopsies with rare apoptosis.

AIMS: The risks of immunosuppression and the non-specific nature of rare crypt apoptosis has led to debate over the lower threshold for histological diagnosis of colonic graft-versus-host disease (GVHD). A recent study proposed the diagnostic category of indeterminate for GVHD (iGVHD) for cases with six or fewer apoptotic bodies per 10 crypts. Our aim was to assess colon biopsies with iGVHD histology to determine whether the diagnosis was retrospectively predictive of the decision to treat, and to correlate these findings with endoscopic and clinical findings. METHODS AND RESULTS: A retrospective search was performed for colonic biopsies taken to evaluate for GVHD from 2008 to 2014. Biopsies were blindly reviewed for the maximum number of apoptotic bodies per 10 contiguous crypts, evidence of crypt dropout, and ulceration. Clinical information was collected through chart review. One hundred and twenty-two biopsies from 84 transplant patients were included. Forty-seven cases met the histological criteria for iGVHD. Patients with an original diagnosis of iGVHD were more likely to be managed conservatively than those with a diagnosis of grade 1 GVHD (25% versus 0%). Eight symptomatic patients reclassified as iGVHD had resolution of symptoms without increased immunosuppression. A clinicopathologically similar group of 10 patients with iGVHD histology, normal or subtle endoscopic findings and no evidence of GVHD at other organ sites were treated with increased immunosuppression. On multivariate analysis, the original diagnostic category was the most significant predictor of the decision to treat. CONCLUSION: The use of the diagnostic category iGVHD alerts clinicians to the presence of minimal crypt apoptosis, and allows treatment based on clinical judgement.