Graft vs. host disease: 6 things to know about this stem cell transplant side effect

Between 20% and 70% of patients who receive an allogeneic stem cell transplant as a part of their cancer treatment will develop at least a mild case of a condition called graft vs. host disease, or GVHD.

But what is graft vs. host disease, exactly, and why does it happen? How can it be prevented and treated?

We spoke with stem cell transplant specialist Amin Alousi, M.D., director of MD Anderson’s GVHD program. Here’s what he had to say.

What is graft vs. host disease?

Graft vs. host disease is a treatment side effect that sometimes develops in patients with leukemia, lymphoma, or other blood- or lymph-based cancers who’ve had an allogeneic stem cell transplant.

These patients receive healthy, blood-forming stem cells from a donor after being given chemotherapy and/or radiation therapy to destroy their own immune system and treat their cancer. The donor’s cells then engraft themselves in the patient’s bone marrow and start rebuilding their new host’s immune system by generating new white blood cells, red blood cells and platelets.

GVHD occurs when the donor’s immune cells recognize proteins expressed by a patient’s tissues and organs as foreign and attack them as if they were invaders.

What are the symptoms of graft vs. host disease?

It really varies depending on the type of GVHD and individual.

Acute GVHD typically occurs within the first few months after a stem cell transplant and has a distinct presentation that can include:

• skin rash
• nausea
• vomiting
• diarrhea
• abnormal liver function, as shown by elevated liver enzymes in blood tests

Chronic GVHD occurs on average about six months after a stem cell transplant. Often, this disease resembles autoimmune disorders that can happen outside of the transplant setting, such as Sicca Syndrome, lichen planus or scleroderma. 

Chronic GVHD can appear in many different ways and affect many different areas of the body. For instance, a patient might simultaneously have dry eyes, mouth ulcers, skin scarring, or other problems associated with the lungs, liver or genitals.

Can GVHD be prevented?

Multiple steps are taken to minimize the risk of GVHD. This includes selection of a donor that best matches the patient (meaning they share the same tissue proteins) and drugs designed to suppress the donor’s immune cells in the patient. But it’s important to remember that even with those drugs, GVHD can still occur. So, we’re actively looking at better ways to prevent it.

One of my colleagues, Rohtesh Mehta, M.D., is participating in a national clinical trial in which the donor stem cells are enriched with special cells called “regulatory (tolerizing) T-cells” as a method of preventing GVHD.

Another close collaborator, Robert Jenq, M.D., performs cutting-edge research studying the role of disruptions in the gut microbiome and the development of GVHD. Together, we’re developing trials to restore a healthy microbiome and prevent GVHD.

And, I’m chairing a very large national clinical trial that’s exploring whether giving patients with high-risk acute GVHD a serum protein called alpha-1 antitrypsin can resolve acute GVHD and improve survival when compared to standard treatment alone.

This is all really exciting stuff, and could change the whole paradigm for GVHD.

How does MD Anderson treat patients with GVHD right now?  

It varies from patient to patient, of course, because everyone is different. But GVHD can create chronic conditions that severely impact patients’ quality of life. So, our goal is to treat those symptoms, and restore our patients’ quality of life.

We’ve assembled a large, multidisciplinary GVHD team here at MD Anderson to do just that, with providers from virtually every department: dermatologists for skin disorders, pulmonologists for lung disorders, ophthalmologists for eye disorders, pelvic floor therapists for genital issues, and so on.

And all of these team members specialize in GVHD, so they’re familiar with how it manifests in each particular area. There are not many clinics like this in the United States.

What are the latest advances in the treatment of GVHD?

Two targeted therapy drugs were recently approved by the Food and Drug Administration (FDA) for the treatment of patients with chronic GVHD. One is KD-025, or belumosudil, and the other is ruxolitinib. Both are immune modulators that change the way T cells function, making them less inflammatory and more tolerant of tissue differences. Belumosudil also targets fibrosis, or scarring, pathways to reverse or halt this manifestation of GVHD.

We’re also studying a drug called itacitinib as an alternative treatment to steroids in patients identified as having low-risk acute GVHD, based on a blood test. Additionally, my colleagues, Partow Kebriaei, M.D., and Elizabeth Shpall, M.D., are conducting a cellular therapy clinical trial with umbilical cord-derived mesenchymal stem cells. It’s for patients with acute GVHD that has failed to respond to standard therapies.   

What’s the one thing you’d like patients to know about GVHD?

I’ve been caring for patients with GVHD for more than 20 years. And when I started out, no one wanted to do this type of research. At the time, there were no existing therapies to help patients get better. It was viewed as a lost cause.

Today, we have three different FDA-approved drugs available to treat patients with various forms of GVHD. And the field has evolved so much. Great advances are still happening.

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