American Society of Hematology Annual Meeting

Immunohistochemistry Identifies Steroid-Refractory From Steroid-Sensitive GI GVHD

Avatar photoBryant Furlow
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Rarely, patients with prostate cancer will develop metastases to the gastrointestinal tract, which l
Rarely, patients with prostate cancer will develop metastases to the gastrointestinal tract, which l
Researchers used multiplexed IHC to identify steroid-sensitive GI aGVHD vs steroid-refractory GI aGVHD, a life-threatening late effect of HCT.

Highly multiplexed immunohistochemistry (IHC) can predict steroid-refractory gastrointestinal acute graft-versus-host disease (GI aGVHD), a life-threatening complication of hematopoietic cell transplant (HCT), according to research presented at the ASH Annual Meeting 2023.

“We used multiplexed IHC to interrogate the immune cells associated with GI aGVHD, with 2 major findings,” said study coauthor Victor Tkachev, MD, of Massachusetts General Hospital and Boston Children’s Hospital. “First, we found that rare apoptosis is associated with superior overall survival even without steroid treatment and with minimal immune infiltration. And most importantly, by creating a multiplex IHC pipeline, we developed an assay capable of accurately classifying steroid-sensitive and refractory aGVHD from standard-of-care biopsy specimens.”

(Rare apoptosis is a histologic finding associated with GI aGVHD involving scattered apoptotic cells in GI epithelial crypts, in the absence of significant inflammatory changes.)

“Patients with steroid refractory GVHD account for much of mortality from this disease,” Dr Tkachev said. 

He and his coauthors used IHC to clarify the immunologic mediators of GI aGVHD and to develop an assay predicting steroid-sensitive and steroid-refractory aGVHD from endoscopic biopsies. They did this with a large clinical cohort of 551 patients who underwent first HCT at Boston Children’s Hospital between 2014 and 2021. The analysis was limited to sigmoid colon biopsies, and patients with evidence of other types of GI inflammation, including infections and drug effects, were excluded from analysis.

“Sixty patients had evidence of GVHD-associated inflammation and 22 were given a diagnosis of rare apoptosis,” Tkachev said. “Importantly, there is no universal consensus of how to manage the rare apoptosis diagnosis. Some centers treat these patients with steroids. However, in our center it’s very rare to treat these patients with steroids. In fact, only 3 of these 22 patients receive steroids, and all were steroid-sensitive.”

Two-year overall survival (OS) was 89% for patients with no GI inflammation vs 86% for those with rare apoptosis, confirming the “benign nature” of rare apoptosis, Dr Tkachev noted. However, 2-year OS was only 58% for patients with steroid-refractory aGVHD, confirming the high risk of death associated with refractory disease. 

There was a “striking” lack of T-cell infiltrates in the biopsies of patients with rare apoptosis, Dr Tkachev noted, with significantly lower CD3, CD4, and CD8 T-cell densities in these patients.

Using immune infiltrate cell type ratios (eg, CD8/CD68, and CD8/epithelial cell ratios), IHC identified patients who developed steroid-sensitive vs -refractory aGVHD. That statistical classifier for these ratios showed a specificity of 0.692 and a very high sensitivity of 0.929. Accuracy was 0.815.

“This analysis could identify patients who will develop steroid resistant refractory GVHD with a low false negative rate,” he said. 

Disclosures: The study was supported by Regeneron Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Rosenbaum S, Fiaschi N, Lim WK, et al. Highly multiplexed immunohistochemistry can predict steroid refractory gastrointestinal (GI) acute GVHD at the time of endoscopy. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 478.