Overview of Graft-vs-Host Disease (GVHD)

Yi-Bin Chen, MD: Hello, and welcome to this OncLive® Peer Exchange® titled “Advances in the Management of Graft-vs-Host Disease.” I’m Dr Yi-Bin Chen, the director of the bone marrow transplant program at Massachusetts General Hospital in Boston, Massachusetts. Joining me in this discussion are my colleagues. Panelists, would you each introduce yourselves?

Hannah Choe, MD: Hi, I’m Hannah Choe. I’m an assistant professor at The Ohio State University in Columbus, Ohio.

Nelson J. Chao, MD, MBA: I’m Nelson Chao. I’m the program director at Duke University School of Medicine in Durham, North Carolina.

Sophie Paczesny, MD, PhD: I’m Sophie Paczesny. I’m a professor at the Medical University of South Carolina in Charleston, South Carolina.

Yi-Bin Chen, MD: Thank you. We’re going to discuss topics pertaining to the diagnosis and treatment of acute and chronic graft-vs-host disease. We’ll discuss the latest research and the effect of clinical trials on treatment selection and patient management. Let’s get started on our first topic. To start, we should set the table and talk about what graft-vs-host disease is. Nelson, could you give us a brief overview?

Nelson J. Chao, MD, MBA: I tell my patients all the time that graft-vs-host disease is exactly what those words say. It’s the graft, which are the donor cells, vs the host, which is the patient. In that setting, the donor cells get into the recipient, the patient, and recognize antigens that are different between itself and the patient, and that starts an immunological process of the graft attacking the host.

In the acute setting, which is what happens early on, a strong cytokine-driven process by the T cells causes disease in the skin, gut, and liver. In the chronic sense, it’s much more of an autoimmune-type process. T cells are critical to start it, but afterward, there are many other cell types that probably contribute to chronic graft-vs-host disease. On the negative side, it certainly can cause morbidity and mortality. On the positive side, because of the host leukemia or lymphoma, the tumor antigens are also new to the donor. These donor cells can recognize these tumor antigens as foreign and kill tumor cells as well, giving the graft-vs-leukemia and graft-vs-tumor effect.

Yi-Bin Chen, MD: Would it be fair to say that you tolerate some graft-vs-host disease in your patients, knowing that it may provide that effect?

Nelson J. Chao, MD, MBA: Yes. We’d all like to have some graft-vs-host disease, which gives us this graft-vs-leukemia effect. Our problem is that we don’t have a way to fine-tune that, so when it happens, it’s grade 4, and patients can die from it.

Yi-Bin Chen, MD: Let’s talk a little about how patients present. It’s interesting. When I talk with my patients before transplant, and I describe the risks and try to talk about graft-vs-host disease, they often ask, “What’s it like if I get it?” Acute and chronic graft-vs-host disease present with different symptoms. Acute graft-vs-host disease generally happens in the first 3 to 6 months, but it can happen later. It usually involves the skin with what I call an angry red skin rash. It involves the GI [gastrointestinal] tract, mainly lower GI tract disease as diarrhea. There’s upper GI involvement, which could be persistent nausea and anorexia. And there’s liver involvement, the least common of those, which presents as asymptomatic elevations in your liver function tests.

Chronic graft-vs-host disease is different. As you heard Dr Chao say, it’s more of an autoimmune disease. It can resemble classic autoimmune disease as dry eyes and dry mouth. The skin rash is less angry. It’s more like eczema. It can affect almost any organ and can have collateral autoimmune disease manifestations, like nephrotic syndrome, where your kidneys lose protein. The 2 most difficult manifestations for us in chronic graft-vs-host disease are scleroderma, where parts of the fascia, or the skin, get very thick and can limit range of motion, and pulmonary involvement, which is a syndrome called bronchiolitis obliterans. Those are the most difficult manifestations to treat.

When patients present with symptoms, they often ask, “How do I know if this is graft-vs-host disease?” That gets at, “What’s the diagnosis?” While we do often biopsy tissues, the diagnosis of graft-vs-host disease remains a clinical diagnosis. It remains taking into account the patient’s symptoms, where they are, what kind of transplant they had, and what their baseline symptoms are to try to make a diagnosis. Biopsies of tissues can help—they can have supportive findings—but the diagnosis remains clinical.

Transcript Edited for Clarity