Diagnosis of Chronic GvHD

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EP: 1.Diagnosis of Chronic GvHD

EP: 2.Overview of Steroid-Refractory Chronic GvHD

EP: 3.Switching Therapies in Steroid-Refractory Chronic GvHD

EP: 4.Treatment Options for Steroid-Refractory Chronic GvHD

EP: 5.Sequencing Therapies in Steroid-Refractory Chronic GVHD

EP: 6.REACH3 Trial in Steroid-Refractory Chronic GVHD

EP: 7.Clinical Implications from REACH3 in Steroid-Refractory Chronic GVHD

EP: 8.Future Directions for the Treatment of GvHD

EP: 9.Recap: Earlier Detection May Be Key to Treatment Advances in Chronic GVHD

Matt Fowler: Hello and welcome to this Contemporary CancerNetwork® OncView™ program titled, “Advances in Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease.” I’m Matthew Fowler, associate editor with CancerNetwork®. We have with us today Dr Yi-Bin Chen, director of the BMT [Blood and Marrow Transplant] Program at Massachusetts General Hospital in Bosto], Rogers Endowed Chair, and associate professor of medicine at Harvard Medical School. Thank you for joining us today, Dr Chen. Let’s get started.

The first segment we’re looking at is diagnosis of chronic GvHD [graft-versus-host disease]. Could you generally talk about how chronic GvHD is diagnosed?

Yi-Bin Chen, MD: The diagnosis of chronic graft-versus-host disease remains a wholly clinical diagnosis. There is no gold standard, noninvasive blood test, imaging, or anything like that. There are a lot of supportive tests that we can do depending on the organs involved, but it’s a clinical diagnosis. A lot of us have experienced seeing patients with chronic graft-versus-host disease and are able to recognize it. It honestly starts by educating our patients so they’re able to report the symptoms that are concerning for chronic graft-versus-host disease. More often than not, when we diagnose chronic GvHD, our patients have had it for a significant period of time and just have not reported it to us. Chronic GvHD happens during a time when we have started to see patients less frequently, certainly less than the weekly follow-up that we do in the first few months right after transplantation. It starts with educating the patient so that they know what to call about or what to bring up in their visit, but then it comes down to actually talking to the patient and asking the right questions. Usually, you run through the most common organs involved, including the eyes, mouth, skin, joints, breathing, and so forth. It is a conversation with the patient to draw out what may be concerning, and then a thorough physical examination focusing on these organs as well can yield findings that are concerning for graft-versus-host disease. I think once you have suspicion for certain organs, then certain tests can be done, though oftentimes just the conversation and the appearance on a physical exam is enough for diagnosis.

Matt Fowler: You already mentioned some of the organs that are typically involved, but could you talk about some of the common symptoms that you see with chronic GvHD?

Yi-Bin Chen, MD: Sure. The most common organs involved are the eyes, mouth, and skin. The eyes and mouth are the classical Sicca syndrome. It mimics the autoimmune disease Sjogren syndrome, so the eyes are often dry. That often is the first symptom. Patients complain of other symptoms as well, including a grittiness, including despite how much they blink or use eye drops, they always feel like they have particles of sand in their eyes. Some patients have pain, but most of it is a dryness or grittiness. That’s the first sign of irritation. With the mouth, there is a dry mouth sensation. Now, they may not come in saying “I have a dry mouth.” They may come in saying, “I’m thirsty all the time” or “when I eat certain foods, I have to drink a lot of water to be able to swallow,” and so forth. These are the symptoms that they may complain about. With the skin, there is a visible symptom of a skin rash. Usually, when it evolves into scleroderma on the superficial skin or deep down to the fascia, then you start asking about range of motion, and the symptoms are that there are certain joints or movements that are restricted, and so forth. If the lungs are involved, there is a syndrome called bronchiolitis obliterans syndrome, and patients can present with a cough, shortness of breath, or dyspnea on exertion. Those are the more common symptoms that we run through when we see patients in follow-up to try to detect if there’s any chronic graft-versus-host disease developing.

Matt Fowler: What are some of the tools used for risk assessment in staging for chronic GvHD?

Yi-Bin Chen, MD: This has been a big effort over the last couple of decades. Chronic GvHD is a very heterogeneous disease, and every patient has different manifestations and a different number of organs involved. That has created a difficult dynamic to not only communicate, but also to conduct well-designed clinical trials for improvement. The best tools that we have for risk assessment and staging right now are based on the NIH [National Institutes of Health] consortium that meets every several years. They’ve created a grading system for every organ that can be potentially involved. This has allowed us to conduct clinical trials and communicate. It may not be the most practical instrument to use in everyday clinical practice, because in all honesty, it takes effort and time to do the whole assessment. The assessment remains imperfect. That’s not a knock against anybody who helped in developing it; it’s just that there is a good amount of subjectivity in that assessment, and that’s inherent in the disease itself. It’s helpful to have your previous assessment next to the one you’re doing, so you can understand how you graded it previously to be able to best judge the assessment.

Those are the best tools we have right now for grading assessment and severity. We don’t have really great tools or biomarkers to risk-stratify patients in terms of prognosis. We’re still stuck here in looking at clinical phenotype to prognosticate patients. While that definitely has a correlation, that may not be the best biological correlate for how to risk-stratify patients, and it’s an active area of research to develop those tools.

Transcript Edited for Clarity