An Overview of Graft vs Host Disease (GvHD)

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EP: 1.An Overview of Graft vs Host Disease (GvHD)

EP: 2.Regimens Used for GvHD Prevention

EP: 3.Clinical Implications of the Phase III BMT CTN 1703 Trial

EP: 4.Future of Acute GvHD Prevention

EP: 5.Acute GvHD: Clinical Presentation, Risk Factors and Treatment Options

EP: 6.Steroid Refractory Acute GvHD and REACH Trials

EP: 7.Novel Agents in Acute GvHD

EP: 8.Defining Chronic Graft vs Host Disease (GvHD)

EP: 9.Treatment Options for Chronic GvHD

EP: 10.Treatment Options: Steroid-Refractory GvHD

EP: 11.Future of Chronic GvHD

EP: 12.GvHD: Advice for Patients

Transcript:

Corey Cutler, MD, MPH FRCPC: Hello and welcome to this OncLive® Peer Exchange entitled, “Expert Perspectives on the Current State of Graft Versus Host Disease.” I’m Dr Corey Cutler, the medical director of the stem cell transplant program at the Dana-Farber Cancer Institute, and an associate professor of medicine at Harvard Medical School. Joining me in this discussion are my colleagues, Dr Yi-Bin Chen from Massachusetts General Hospital, Dr Hannah Choe from Ohio State University, and Dr Doris Ponce from Memorial Sloan Kettering Cancer Center. I’m going to ask each of you to introduce yourselves.

Yi-Bin Chen, MD: Thank you, Corey. My name is Yi-Bin Chen. I direct the transplant program at Massachusetts General Hospital in Boston.

Hannah K. Choe, MD: Hi, I’m Hannah Choe. I’m an assistant professor at Ohio State University in Columbus, and I’m the director of the GVHD program there.

Doris M. Ponce, MD: Thank you. My name is Doris Ponce. I’m an associate professor and I am the GVHD program director of adult BMT [bone marrow transplant] at Memorial Sloan Kettering.

Corey Cutler, MD, MPH FRCPC: Welcome, all of you. Let’s get started on our first topic. Today, we’re going to be talking about a number of discussion topics relevant to graft versus host disease [GVHD]. We’re going to start by talking in general about GVHD and why it occurs. What are the settings we’re seeing it in? Why don’t you give us a little bit of a background, Yi-Bin, on why we get graft versus host disease, and what diseases we’re treating at the time of inducing GVHD?

Yi-Bin Chen, MD: These days, the vast majority of our patients have an underlying diagnosis of a hematological malignancy, and that’s why they’re referred to undergo hematopoietic cell transplantation. There is a minority who have nonmalignant diseases, but the vast majority have a hematological malignancy. Even though the chemotherapy or the radiation we give in the week before transplant has some disease-modifying effect, most of us believe that the reason a hematopoietic cell transplant is potent and potentially curative for the majority of these patients is something called the graft versus malignancy effect. This is an immunologically driven effect where the donor cells are able to eradicate any residual malignancy that is left behind. The issue with that, or the tax for that, is that sometimes the donor cells not only attack the patient’s malignancy, but they also attack the patient’s normal body. That gives rise to this complication called, graft versus host disease.

Corey Cutler, MD, MPH FRCPC: Hannah, are there any specific risk factors that make a patient more or less prone to developing graft versus host disease?

Hannah K. Choe, MD: The biggest one would be the degree of HLA match. When we try to identify donors for stem cell transplantation, we use HLA matching to identify patients who are more similar genetically as a donor versus recipient. When there’s more of a mismatch with that HLA degree, then there’s more of a likelihood of identifying the recipient as foreign, and there’s more of a divide between the graft, or a bigger jump between graft versus the host. That directly puts the patient at risk of developing graft versus host disease. Other risk factors include age. Increased age does preclude higher risk for graft versus host disease, and sex mismatch as well. Essentially, any more degree of a [mismatch] increases the risk for GVHD.

Dr. Corey Cutler, MD, MPH FRCPC: Doris, what about some of the other risk factors that perhaps we can modify as the transplant clinician, things like the donor source, or conditioning agents? Do any of those factors influence the rate of graft versus host disease?

Doris M. Ponce, MD: Yes, certainly. Donor source is important. We are learning about increasing mismatch in related donors as part of our platform and learning how can we use alternative donor transplantation to make transplants safer, so donor selection is important. Also, we’re learning about how old the donor should be and what would be ideal if we have a younger donor versus an older donor, and if that could increase your risk of graft versus host disease as well as if it is related or unrelated. Another thing we could consider is how intensely we want to put our patients into conditioning. Higher conditioning is associated with more tissue injury, and that can translate into more immune reactivation and eventually, graft versus host disease. Those will be additional factors.

Corey Cutler, MD, MPH FRCPC: Is it a static fixed rate of GVHD? Are there things you can do, Yi-Bin, to try to modulate that risk? How do you prioritize these factors when deciding on GVHD risk for your individual patient?

Yi-Bin Chen, MD: This is a difficult question because a lot of us feel like we are in more control than we actually are. There are some patients where you have more of an appetite for graft versus host disease, perhaps, because they have a higher biological risk disease where you feel like you need to encourage this graft versus malignancy more. The traditional teaching has always been, we cannot separate graft versus host disease from graft versus malignancy, though that may be changing. Along the way, as you treat your patient, we all feel like we have some semblance of control in how we manage the immunosuppression, what levels we run certain medications at, and how well the patient is in terms of nourishment and nutritional status. One of the most popular risk factors of interest right now is the microbiome. The microbiome refers to the diversity of bacteria in one’s gut. Many associative studies have suggested that a nondiverse microbiome, or a narrow diversity microbiome, called dysbiosis, is associated with an increased risk of graft versus host disease. Whether there’s a cause-and-effect relationship, we need to figure that out, or if it’s just a marker of a patient at risk. There is plenty of research to see if we can modify the microbiome diversity and perhaps, modify the risk of graft versus host disease.

Transcript edited for clarity.