Graft-versus-Host Disease of the Gut: A Histologic Activity Grading System and Validation.

Publication Type:

Journal Article


Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (2017)


The pathologic interpretation of gut biopsies in hematopoietic cell transplant recipients to assess graft-versus-disease (GVHD) is well accepted and supplements clinical and endoscopic findings. However, the histologic activity grading of GVHD is controversial, with attempts to predict prognosis or response to treatment largely unsuccessful. GVHD is being diagnosed earlier in its course, raising the possibility that the pathologic grading system can be profitably modified. We have developed a histologic activity grading system designed to replace the commonly used modified-Lerner grading systems. Our system stratifies the low-level Lerner grade I category into 4 activity grade categories, based on the average frequency of apoptotic cells. The results are expressed as ordinal categories, GVHD of minimal, mild, moderate, severe histologic activity, or severe histologic activity with destruction (activity grades 1-5). In a retrospective study, 87 consecutive cases with 201 post-transplant specimens (median 48 days, range 18-1479 days) of stomach, duodenum, and colorectum, which had been activity graded at the time of the original diagnosis, were studied. Most of the biopsies diagnosed as GVHD were low grade-minimal (11%) or mild (71%) histologic activity. We hypothesized that the higher activity grades should be associated with more therapeutic intervention. The odds of increased therapy in the combined all-site specimens were increased as the activity grade increased [odds ratio (OR) = 2.9 (1.9-4.5), p=<.0001]. Thus, our grading system was validated. To investigate whether the activity grade was associated with therapy within the formerly undivided Lerner grade I category, the analysis was restricted to these 174 all-site specimens. The validation result was similar [OR = 3.1 (1.3-7.2), p=.009]. This result interestingly suggests that there is useful information hidden in the Lerner grade I category which could potentially guide immediately actionable treatment decisions. This histologic activity grade system has been in use at our institution for over 2 years, with good acceptance.