Clinical Scenario: A 53-Year-Old Man With Chronic GVHD
Nelson Chao, MD, MBA, presents the clinical scenario of a 53-year-old man with chronic graft-versus-host disease and highlights the complexities of distinguishing between symptoms of acute and chronic GVHD.
Nelson Chao, MD, MBA: Welcome to this Cancer Network program titled "Treatment Selection and Sequencing for Chronic Graft-versus-Host Disease." I'm your host, Nelson Chao. I run the division of hematologic malignancy cell therapy at Duke University and am also joined by three colleagues who I'd like to ask to introduce themselves.
Erin Kopp, NP: Hello, my name is Erin Kopp, and I am the Director of Advanced Practice at City of Hope Duarte. I am a nurse practitioner who has been in transplant for the last nine years and was lucky enough to work with a chronic graft-versus-host disease clinic where we interact with patients who have long-term effects post-transplant.
Catherine Lee, MD, MS: Hi everyone. My name is Catherine Lee. I am an adult blood and marrow transplant physician currently at the Fred Hutchinson Cancer Center. I am a faculty member of the long-term follow-up program where I see many patients with chronic nephropathy and other late complications of transplantation.
Hana Safah, MD: My name is Hana Safah. I am a professor of medicine at Tulane Medical School, and I am the director of the Stem Cell Transplant program at Tulane, as well as the hem malignancy program. I also run the clinic of GvHD and the long-term survivorship clinic post-transplant. I'm happy to be here.
Nelson Chao, MD, MBA: Thank you all. Today we're going to discuss graft-versus-host disease through the context of two clinical scenarios. We're going to discuss prophylaxis, symptom assessment, and treatment options for chronic graft-versus-host disease. So, let's begin. We're going to start with a case. The first case is a 53-year-old man who undergoes myeloablative conditioning, matched unrelated donor, peripheral blood stem cell for acute myeloleukemia. He receives tacrolimus and methotrexate as GvHD prophylaxis. His donor's CMV is serum-positive. She's a 45-year-old woman with two children. The transplant goes well, but by day 25, acute GvHD of the skin is diagnosed. It's successfully treated with a steroid initiation taper. Three months post-transplant, the patient has a bone marrow test that shows he is in complete remission. Six months post-transplant, he has normal blood counts but shows up with skin changes with hyperpigmentation. About one-third of each arm shows lichen implants with superficial sclerosis features. You're able to pinch the skin on the lower trunk and the lower extremity. There are about 15% body surface areas involved. No decrease in FEV1 or DLCO in his pulmonary function test. So, we started him on 0.5 milligrams per kilo per day of prednisone, and we see improvement after seven days. To start, we need to define graft-versus-host disease. We historically have called it acute and chronic based on time. I think we've moved away from that. The etiology is a continuum, although the clinical manifestation is really quite different. Acute GvHD appears to be much more of an acute hyper-inflammatory type response, whereas chronic GvHD seems to be much more of an autoimmune-based response. Both are T-cell dependent, but in the chronic setting, T cells are not the major contributor for many of the manifestations. We all recognize today that there's an overlap syndrome where acute can happen certainly late, and chronic can happen much earlier than day 100. I'm going to open this to my colleagues and ask what their experience has been in terms of looking at overlap versus late acute versus early chronic.
Hana Safah, MD: So, you are right. In the beginning, during our fellowship, we were trained that 100 days delineated acute from chronic. Then we learned that this timing from graft infusion does not truly speak to what kind of GvHD we're dealing with. It's more about the pathophysiology behind it and the presentation. I look at the overlap as those who present with the inflammatory type of acute GvHD signs and symptoms in patients who have chronic GvHD manifestations or disease presentation. Usually, there is some controversy regarding these patients with this overlapping GvHD. We know that they don't do as well as patients with just acute or just chronic. So, this overlap, we're seeing it more and more. We're seeing it more probably with the non-myeloablative, with later recovery of graft. So, we see it. We're trying to understand the pathophysiology. Is the patient experiencing autoimmunity plus the ongoing inflammatory process? But we know from our practice that these patients usually don't do as well and don't respond as well to the treatment compared to acute versus chronic.
Nelson Chao, MD, MBA: Thank you. Catherine, you were going to say?
Catherine Lee, MD, MS: I completely agree with both of you. I think we'll find it more interesting as we test and develop new prophylactic strategies for graft-versus-host disease, such as post-transplant cyclophosphamide, abatacept, and perhaps, in the near future, ruxolitinib. I think it'll be interesting to see the kinetics of the development of acute and chronic graft-versus-host disease and how we see both occur together, which has historically been called overlap syndrome. So, we still have much more to learn in the upcoming years.
Erin Kopp, NP: And I think, to both of your points, understanding the etiology and what's happening in the patient lends itself to a better understanding for the patient, the caregivers, and all of the providers who are interacting with the patient. When we first started learning about graft-versus-host disease, it drove our assessment. If you're only thinking that in the first 100 days, you're going to see acute symptoms, it's easy to overlook them if they're at day plus 150. Helping patients and caregivers understand that these symptoms can happen throughout the continuum and how important it is to have that relationship with your providers and be able to communicate symptoms as they come up is crucial. Because if it's confusing or still not clear-cut for the physicians and advanced practice providers, it's likely even more confusing for the patients. One key to better outcomes is ensuring that we're all on the same page.
Nelson Chao, MD, MBA: I think that's a perfect point because many of these patients are no longer at our center.
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