Inside the Clinic: Acute Graft-versus-Host Disease - Episode 2

Classifying GVHD and Predicting Risk of Events

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Yi-Bin A. Chen, MD: Over the last decade, there have been many agents tried for graft-vs-host disease [GVHD], for both prevention and treatment. It’s only through the last few years that I think we’ve started to make some advancements. But to discuss those, I think it’s helpful to understand how acute graft-vs-host disease is classified, and mostly in terms of severity. Colleen, are you able to share that with us?

Colleen M. Danielson, NP: When we think about classifying acute graft-vs-host disease, the 3 organs that you mentioned are involved: skin, GI [gastrointestinal tract], and liver. For skin, we classify that based on the rash and the total-body surface area that is involved. With the GI tract, we think about the volume of diarrhea. That’s how we classify lower-GI GVHD. With the liver, we look at the total bilirubin. We use that to classify liver graft-vs-host disease. Each organ then gets staged based on a 1-to-4 scale. We take into consideration those 3 things that we just mentioned: total-body surface area for skin, diarrhea for GI, and total bilirubin for liver. We get a combined overall grade when we think about all those organs that can potentially be involved at the same time. That’s really how we think about classifying the severity of acute graft-vs-host disease.

Yi-Bin A. Chen, MD: You can see that we still use fairly clinical means to classify the severity of acute graft-vs-host disease. Part of the problem in the development of novel agents and the success of trials has been the inability for us, as clinicians, to take this grading system and be able to predict how patients will do, and thus to prognosticate and even risk stratify patients and develop different treatments for different types of patients. Zach, do you want to talk about how we risk stratify patients now in trials, and perhaps more novel ways in the future?

Zachariah M. DeFilipp, MD: Sure, Yi-Bin. In recent years, there have been 2 main developments in the risk stratification of patients. The first is a clinical score referred to as the Minnesota Acute GVHD Risk Score, which basically evaluates the organ involvement at the time of an acute GVHD diagnosis. This score is able to risk stratify patients into 2 cohorts: a standard-risk cohort and a high-risk cohort.

High-risk patients, as compared with those standard-risk patients, are less likely to respond to initial steroid therapy and have an increased risk of dying, as related to what we would term nonrelapsed mortality, which is usually driven by their GVHD disease.

What’s nice about the Minnesota Acute GVHD Risk Score is that it’s an easy tool that’s available for all clinicians, and it’s already regularly being incorporated into GVHD clinical trials. Another novel way to approach risk stratification is through the use of blood biomarkers. Some of the most extensive research on GVHD blood biomarkers has been done through the Mount Sinai Acute GVHD International Consortium, also known as MAGIC. With their research, we have helped identify 2 very important blood biomarkers: REG3-alpha and ST2. Algorithms have been created using these 2 blood biomarkers that can risk stratify patients at different points after their transplant. They can be used either at the diagnosis of acute GVHD or early on in GVHD treatment to predict who’s more likely to respond or less likely to respond to initial treatment with steroids.

They can also be used even earlier on in transplant in asymptomatic patients to risk stratify someone who’s more likely to develop more severe graft-versus-host disease. Both of these tools—the clinical score and the blood biomarkers—are helping us in our stratification of patients. The overall hope is that we’ll be able to individualize treatment strategies for patients. For example, for a high-risk patient we might be able to intensify their therapy earlier on; and for a low-risk patient, we may be able to approach them with a steroid-sparing treatment to spare them the toxicities of typical GVHD treatment.

Transcript Edited for Clarity