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

Abstract

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.