Overview of Graft-Versus-Host Disease

Corey S. Cutler, MD, MPH, FRCPC: GVHD [graft-vs-host disease] is an immunologic reaction that occurs after transplant when you use a foreign immune system put into a new host body. That immune system recognizes the body it is now in, the host, and determines that it’s foreign and tries to reject it. GVHD remains the most important complication after transplant. It is the most serious and important cause of decrease in overall survival after transplant, second only to relapse of the original malignancy. GVHD remains critical to the success of transplantation. One of the major goals of our research program is to try to improve GVHD outcomes.

Yi-Bin Chen, MD: Allogeneic hematopoietic cell transplantation is an aggressive, potentially curative treatment for many patients with advanced hematological malignancies. The way we think transplant works is that we replace the host’s hematopoietic or blood system with the donor’s blood system. When the donor’s blood system grows up, it includes white blood cells, red blood cells, and platelets. When those white blood cells grow up, they form an immune system to help protect the recipient from infection. Ultimately, if there’s any malignancy left, we hope that the donor’s white blood cells are able to attack the malignancy, exerting what we call a graft-vs-malignancy or graft-vs-tumor effect, perhaps the earliest example of immunotherapy. That’s how we think most transplants work in terms of exerting a curative mechanism of action on patients’ malignancies.

The problem is that the patient and the donor, even though they may be either very closely matched or fully matched at the HLA [human leukocyte antigen] sites, are not identical twins. There are differences. The donor’s immune system may grow up to not only attack the patient’s underlying malignancy, but also attack the patient’s healthy body. That is the phenomenon of graft-vs-host disease, where the graft or the donor cells attack the host, which is the recipient. Graft-vs-host disease can be divided into 2 distinct phenomena. One is called acute graft-vs-host disease, which most commonly occurs within the first 6 months after transplantation. It presents as either a skin rash, a lot of watery diarrhea, or liver test abnormalities. Chronic graft-vs-host disease tends to take place after at least 3 months and can continue, ultimately for the remainder of the patient’s life.

Graft-vs-host disease presents a lot of challenges. Everyone receives some sort of prevention against graft-vs-host disease, but even with the best prevention, there is still an incidence of both acute and chronic graft-vs-host disease. Acute graft-vs-host disease is often dramatic and often results in rehospitalization, especially if the lower GI [gastrointestinal] tract is involved. It’s the leading cause of morbidity and early mortality for our patients. Chronic graft-vs-host disease tends to be more indolent, less dramatic, less life-threatening. However, it is more difficult to treat to resolution. Oftentimes, patients are on lifelong medications afterward. For long-term survivors after transplant, chronic graft-vs-host disease is the single thing that affects their quality of life the most. The medications used to treat it and the complications that ensue have a significant effect on their morbidity and even their mortality.

Corey S. Cutler, MD, MPH, FRCPC: We believe we understand most of the risk factors for acute and chronic graft-vs-host disease. Far and away, the most important is HLA mismatch. We know that individuals who receive perfectly matched grafts have the lowest rates of GVHD. Other risk factors include both the donor and recipient age; the drugs we use to prevent graft-vs-host disease, so the prophylaxis agents; sometimes gender, particularly in chronic GVHD; and parity. Then there are less important risk factors, like CMV [cytomegalovirus] serostatus and other very minor factors. Far and away, HLA mismatch is the most important risk factor for both acute and chronic graft-vs-host disease. Acute GVHD was once thought to be an important risk factor for chronic GVHD as well.

Haris Ali, MD: Chronic GVHD happens in patients after allogeneic transplant. The common risk factors are match unrelated or mismatched unrelated donor transplant, myeloablative conditioning regimen, and gender differences between donor and recipient.

Common risk factors for chronic GVHD include the types of the donors. Unrelated donors have a high risk of chronic GVHD compared to related donors. It also depends on the type of the conditioning regimen. People getting myeloablative conditioning, including radiation-based conditioning, have a slightly high risk of chronic GVHD. One of the other factors is gender differences between a donor and the recipient. For example, a male patient getting stem cells from a female donor, especially one who has a history of pregnancy or multiple pregnancies, has a much higher risk of chronic GVHD.

Transcript Edited for Clarity