 There are several risk factors for graft-vs-host disease, the most important of which is of course HLA [human leucocyte antigen] matching. The closer the donor and the recipient are in terms of HLA, the lower the risk of graft-vs-host disease [GVHD]. There are some other factors we can control. The age of both the donor and the recipient is an important risk factor. So is gender—both matched and using female donors are risk factors for graft-vs-host disease. Things like CMV [cytomegalovirus] serostatus traditionally have been considered risks but probably are less important these days. We also like to look at things like stem cell source. Peripheral blood stem cells have a slightly higher rate of graft-vs-host disease than bone marrow, which is slightly higher than umbilical cord blood. Some of these factors we can modify, so we can choose who the donor is going to be and what stem cell source. But some of these factors are not modifiable by us. We’re handed the donor and some of these factors, and sometimes we can’t avoid those problems.

 When we speak about the overall incidence of acute graft-vs-host disease, we are generally referring to the percentage of patients who will develop overall grades 2 through 4 acute graft-vs-host disease as that’s the type that’s thought to be medically significant. It’s tough to answer that question because if you look at large studies, the incidence varies depending on a lot of clinical factors. If you summarize all the studies, you can find incidences anywhere from 10% all the way up to 80%. The general rule for a large population of patients undergoing all types of allogeneic transplant is an overall incidence of somewhere between 30% and 40% if you look at large series. In our own institution, we do review our outcomes on an annual basis. Over the last few years, our overall incidence of grades 2 through 4 of acute graft-vs-host disease in the first 6 months is right around 25% to 30%.

 When thinking about the incidence of acute GVHD, it’s important to remember that it’s dependent on several clinical factors, including the doughnut-type transplant as well as the GVHD prophylaxis regimen. There was a recent study published in the last year, BMT CTN 1203, that looked at 4 different types for GVHD prophylaxis regimens.

In that study, the incidence of grade 2 to 4 acute graft-vs-host disease, was in the range of 25% to about 35% for all 4 approaches. That’s similar to what we see at our institution at Massachusetts General Hospital, the incidence of acute graft-vs-host disease is also in the range of 25% to 30%.

 Acute GVHD presents with involvement in general of 3 organs only. We don’t quite understand why that is, but the skin, the gastrointestinal [GI] tract, and the liver are the 3 most commonly affected organs. The skin is present in 60% to 70% of cases of acute graft-vs-host disease, typically presenting with an erythematosus raised or maculopapular rash, often starting on the shoulder girdle, the forearms, and the upper body, and often working its way down. The gastrointestinal tract presents with perfuse watery diarrhea, abdominal cramping. Sometimes involvement of the upper GI tract presents with intractable nausea, anorexia, and things like that. The liver is the least commonly affected organ, presents typically with painless jaundice or hyperbilirubinemia, and patients typically do not recognize that early on. It’s mainly a laboratory finding unless it becomes severe and the patient is truly jaundiced.

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Risk Factors, Incidence & Typical Presentation of GvHD

 Graft-versus-host disease remains a major complication and challenge for patients and for us as transplant practitioners as well. Inherent to the mechanism of why transplant works is what we believe to be an immunological attack on malignancy by donor cells. The risk that comes with that is graft-versus-host disease because patients and donors are different. Even though we obviously try to match very closely, these are different people and there’s always a risk of graft-versus-host disease.

Simply, graft-versus-host disease is when the donor’s white blood cells attack the recipient’s healthy body, and transplant is probably the only setting that we will see this disease in. There are two general types of graft-versus-host disease, classified as acute and chronic. Acute graft-versus-host disease generally happens in the first few months after transplant. This is the time most vulnerable for our patients. They’ve often spent several weeks in the hospital already and they’re emerging at a time when they’re quite weakened. They’re recovering from infections and other complications. If graft-versus-host disease were to happen at that point, it often requires another hospitalization. It’s very difficult medically, emotionally, and physically for our patients to overcome. Chronic graft-versus-host disease generally happens later. In our large series of survivors after transplant, it’s the single most important factor that determines overall quality of life in the long run. As we look to the future of transplant and more survivors, fortunately, chronic graft-versus-host disease is a huge unmet need for us because we do want to maintain their long-term quality of life.

 Graft-versus-host disease is a clinical syndrome that most generally is divided into acute and chronic forms. Historically, the distinction between the acute form and the chronic form was made based on a time mark of 100 days after transplant.

We now know that these two entities, the acute and chronic graft-versus-host disease, are distinct in their clinical presentation as well as in their biology. Acute graft-versus-host disease typically presents earlier on after the transplant and clinically, it manifests in a few cardinal manifestations: a skin rash, diarrhea, nausea, and inflammation of the liver.

Chronic graft-versus-host disease typically presents later on after the transplant and can affect a large number of different organ systems, including the eyes, the mouth, the GI [gastrointestinal] tract, the lungs, the liver, soft tissues, and others.

Usually at its initial presentation it has more of an inflammatory nature, but in more advanced cases we often see a more fibrotic nature, such as is seen in patients who have systemic sclerosis.

Zachariah M. DeFilipp, MD, Massachusetts General Hospital

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Risk Factors, Incidence & Typical Presentation of GvHD

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