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Announcer:
You’re listening to Project Oncology on ReachMD. Here’s your host, Dr. Mary Katherine Cheeley.

Dr. Cheeley:
Welcome to Project Oncology on ReachMD. I'm Dr. Mary Katherine Cheeley. And joining me to discuss how we can tighten the diagnostic window for chronic graft versus host disease, or GVHD for short, is Dr. Zach DeFilipp. He's an Assistant Professor of Medicine at Harvard Medical School and the Director of Blood and Marrow Transplant Clinical Research at Massachusetts General Hospital. Dr. DeFilipp, thanks so much for being here today.

Dr. DeFilipp:
It's my pleasure.

Dr. Cheeley:
Can you give us some background on chronic graft versus host disease and what some of the signs and symptoms are?

Dr. DeFilipp:
Sure. So chronic graft versus host disease is one of the main complications that can occur in patients who receive allogeneic hematopoietic cell transplantation, which is a transplant from a donor with the intention to cure a form of blood cancer or other high-risk blood disorders. In general, graft versus host disease is a complication that occurs because there are differences between the donor and the recipient. And when these new cells come and engraft within the donor, with time, those differences can cause different disease manifestations in the recipient.

There's a form of graft versus host disease that happens early on after transplant, which we call acute graft versus host disease. And this typically happens in the first 3 to 4 months after transplant. But chronic graft versus host disease is something that while we don't see it as early on after transplant, we actually see it over a much longer period of time. So it can begin as early as the first few months. But really, we see it in the first year and even the first few years after transplant.

Chronic graft versus host disease can affect many different organs within the body. The three most common are the skin, the eyes, and the mouth. But we often still see manifestations in the GI tract, the liver, the lungs, and sometimes also the muscles and the joints. The symptoms can begin rather more mildly and kind of slowly progress over time. And often the signs and symptoms are somewhat nonspecific. So we talked about the skin. So we can see skin rashes or other types of skin changes. In the eyes, we often see patients that have dry eyes. In the mouth, we can also see some changes that result in dry mouth. But as you can imagine, with these complex patients who are on medications and have other medical issues, it can be hard sometimes to tease these symptoms out and truly identify them as graft versus host disease.

Dr. Cheeley:
So with those kind of nonspecific things in mind, it almost sounds like you're being a detective when you were younger. What are some of the obstacles that lead to diagnostic delays for these patients?

Dr. DeFilipp:
One of the bigger issues is that graft versus host disease, especially the chronic form, has a lot of mimics. And it is hard to sometimes say this is definitively graft versus host disease. You know, we're always sometimes a little biased as transplant physicians, and when in doubt, we probably lean into the graft versus host disease diagnosis. But it is very important because sometimes patients do actually have a separate medical condition that's causing these issues. I myself have been tricked multiple times. There have been patients that have had dry eyes that when we send them to the ophthalmologist, they ultimately are found to have a separate diagnosis that's not related to graft versus host disease. And then there are patients who have, let's say, elevated liver function tests that could be graft versus host disease, or it could be related to medications, infections, or other complications that are related to the transplant. So identifying these symptoms early and starting to do some testing in order to try to really refine the true etiology of the symptoms is very important.

Dr. Cheeley:
For those just tuning in, you're listening to Project Oncology on ReachMD. I'm Dr. Mary Katherine Cheeley, and I'm speaking with Dr. Zach DeFilipp about disease progression in chronic graft versus host disease, otherwise known as GVHD.

So, Dr. DeFilipp, let's switch gears and look at intervention. When and how should we initiate treatment for these patients?

Dr. DeFilipp:
Yeah, so there's a few things I think about when it comes to initiating treatment for patients with chronic graft versus host disease. And it really has to do with what's the severity of the disease that they have at this point? And those two major kinds of considerations within that are, how many organs are involved? And also what's the severity of the organ involvement?

The standard first-line treatment for chronic graft versus host disease remains corticosteroids, so a medication like prednisone. But we often try to see if we can get the symptoms under control quickly with prednisone. But we really are trying to avoid long courses of high doses of steroids because of all the complications that are related to that.

And we're very fortunate now to have three FDA-approved agents for patients who have chronic graft versus host disease that have not responded in an optimal way to steroids. So we have a lot of good other agents available to help our patients.

Dr. Cheeley:
Are there any early intervention strategies that you can use to reduce diagnostic delays or combat disease progression?

Dr. DeFilipp:
Yeah, so I think one of the things that we do at our institution is we really believe in multidisciplinary care and try to have our transplant recipients see specialists for these different organs that could be involved in order to monitor for any signs or symptoms of disease early on. So we refer all of our patients to ophthalmology for a specialized evaluation to evaluate for any signs or symptoms of chronic graft versus host disease, even if they're asymptomatic.

Another great example is that lung GVHD can be one of the more difficult manifestations to manage. And there's evidence to suggest that early intervention on lung GVHD might be beneficial for patients. So we actually plan for all of our patients to have screening pulmonary function tests done within the first year after their transplant in order to see if we can pick up on any subtle decrease in their lung function that might be a manifestation of graft versus host disease so that we might be able to initiate therapy earlier on in those cases.

Dr. Cheeley:
That's awesome. I love the proactive nature and the multidisciplinary care. Before we close, do you have any final thoughts you'd like to share with our audience?

Dr. DeFilipp:
I think my final thought would be for people just to be aware of chronic graft versus host disease as an entity. Allogeneic transplant and its use in the United States continues to increase every year. And we are now transplanting more patients than we ever have and with better outcomes than we probably have ever had. And with that, the number of transplant survivors and transplant recipients is going to increase. And we're going to see these patients not only in a bone marrow transplant clinic, but also in local follow-up with not only oncologists but also primary care physicians. And I think that being aware of this disease and its different manifestations is important. And I think that the best way to really care for these patients is by working together and communication between the transplant team, the local care providers, and the patient and their family in order to assess for these symptoms early on and to come up with a plan for testing and intervention as needed.

Dr. Cheeley:
This has been such a great discussion. I would love to thank my guest, Dr. Zach DeFilipp, for joining me to discuss early intervention strategies in chronic graft versus host disease. Dr. DeFilipp, it was so nice to have you on the program. Thanks for coming.

Dr. DeFilipp:
It's my pleasure, anytime. 

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