Clinicopathologic Threshold of Acute Colorectal Graft-versus-Host Disease

Gomez, Adam J.; Arai, Sally; Higgins, Julian P T; Kambham, Neeraja

doi:10.5858/arpa.2015-0187-oa

Cited by 15 publications

(6 citation statements)

References 16 publications

(19 reference statements)

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“…An increase in apoptotic bodies was observed in patients without clinically apparent intestinal aGvHD who had macroscopically bland mucosa; this is consistent with our previously published data [ 22 ]. Moreover, patients with histologically more advanced aGvHD who exhibited crypt destruction or mucosal loss were not automatically treated with steroids; thus, our results reinforced the concept of a gray zone in terms of the histologic diagnosis of significant aGvHD [ 7 , 23 ].…”

Section: Discussionsupporting

confidence: 70%

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

et al. 2021

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Acute graft versus host disease (aGvHD) is an important, life-threatening complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). To investigate the value of multiple simultaneous colon biopsies in improving diagnostic accuracy in patients with aGvHD, we retrospectively analyzed 157 patients after alloHSCT. The biopsies were evaluated individually using three established histological grading systems (Lerner, Sale, and Melson). The maximum, minimum, median, and mean histological aGvHD grades were calculated for each patient, and the results were correlated with the Glucksberg grade of clinical manifestation of GvHD, steroid therapy status, and outcome. We found that multiple colon biopsies enhanced diagnostic sensitivity. Moreover, higher histological grades correlated with steroid therapy initiation and refractoriness; the latter particularly occurred when advanced damage was present in all samples and healthy colon mucosa was reduced or absent. On multivariate analysis, the minimal Lerner and Glucksberg grades for intestinal aGvHD were significantly associated with steroid treatment failure. Ninety-nine patients died. The median survival was 285 days after the biopsies were taken. Fifteen patients died from relapse of their underling disorder and 84 from other causes, mostly infection (53 patients) and GvHD (14 patients). Multivariate analysis revealed a significant association between none-relapse mortality and the mean Lerner grade, minimum Melson grade, Glucksberg organ stage, and platelet counts. Thus, we found the Lerner system to be superior to the other grading methods in most instances and histologic evaluation of multiple simultaneously obtained biopsies from the colon to result in a higher diagnostic yield, which helps plan systemic steroid treatment while predicting treatment response and outcome.

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Section: Discussionsupporting

confidence: 70%

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

et al. 2021

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“…This study did exclude the most common causes of such bodies, especially in bone marrow transplant recipients, that is, preconditioning regime, CMV and adenovirus infections, mycophenolate mofetil injury, sodium phosphate bowel preparation and NSAID use 1 7. Like previous studies of apoptosis in GVHD biopsies,4 6–9 we were unable to completely exclude proton pump inhibitor use as another common cause of GI epithelial apoptosis but this drug effect has only been reported in the gastric antrum 10. Finally, it is repeated that our study used stringent clinical criteria (eg, clinical response to GVHD-targeted management) to validate each diagnosis of GI GVHD.…”

Section: Discussionmentioning

confidence: 94%

“…Indeed, raising a defining threshold to increase specificity for diagnosing GI GVHD will usually lead to reduced sensitivity 4. The threshold of 6 apoptotic bodies per 10 contiguous crypts was based on4 and further assessed8 9 using colorectal biopsies only. However, because this threshold yielded very similar sensitivity rates for diagnosing GVHD among our study’s duodenal (81%) and colorectal (84%) biopsies, this threshold appears to be applicable to the duodenum and presumably the small intestine as a whole.…”

Section: Discussionmentioning

confidence: 99%

How many serial sections are needed to detect apoptosis in endoscopic biopsies with gastrointestinal graft versus host disease?

Wong

Marks²

2019

J Clin Pathol

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AimsThe hallmark histological feature of acute gastrointestinal graft versus host disease (GI GVHD) is epithelial apoptosis. This is the first formal evaluation of how many serial sections are required to consistently detect apoptotic bodies in endoscopic biopsies from various GI locations in patients with clinically validated GI GVHD.Methods, results and conclusionsAssessment of 1008 serial sections showed that apoptotic bodies are uniformly distributed among such sections of gastric, duodenal and colorectal biopsies from these patients. Assessment of 59 further biopsies showed that assessing 12 serial sections should suffice to detect GVHD in gastric, duodenal and colorectal biopsies using thresholds of one apoptotic body per biopsy fragment or one apoptotic body per 4 mm2. Assessing 12 serial sections should also suffice to detect GVHD in duodenal and colorectal biopsies using the threshold of 6 apoptotic bodies per 10 contiguous crypts, but it remains uncertain whether this assessment and threshold can be applied to gastric biopsies.

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“…This system is not directly comparable to ours, but appears roughly to correspond to moderate histologic activity under our system. However, the system is insensitive, with Gomez et al reporting in the subset specimens restricted to Lerner grade 1, colorectal GVHD was detected with a sensitivity of 59% [41]. Both Lin and Gomez note that as few as a single apoptotic cell may reflect GVHD, in accord with Nguyen, and suggest a new Lerner indeterminate category to encompass the lower levels of apoptotic activity.…”

Section: Discussionmentioning

confidence: 99%

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

Myerson

Steinbach

Gooley

et al. 2017

Biology of Blood and Marrow Transplantation

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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.

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Clinicopathologic Threshold of Acute Colorectal Graft-versus-Host Disease

Cited by 15 publications

References 16 publications

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

An investigation of the diagnostic, predictive, and prognostic impacts of three colonic biopsy grading systems for acute graft versus host disease

How many serial sections are needed to detect apoptosis in endoscopic biopsies with gastrointestinal graft versus host disease?

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

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