Corey S. Cutler, MD, MPH, FRCPC: Let’s discuss 1 of the most important sets of complications after transplantation. One of the major limitations of a successful transplantation is graft-vs-host disease. Dr Chen, would you mind giving us an overview of graft-vs-host disease and discussing the differences in acute and chronic graft-vs-host disease?
Yi-Ben Chen, MD: For the vast majority of our patients who have a malignant disease, the mechanism of action behind a successful allogeneic transplant, we believe, lies in not only the conditioning therapy we give prior to the transplant but an immunological-based mechanism of action that is called graft-vs-malignancy. The donor’s immune system grows up inside the recipient. If there’s any residual malignancy left, the donor’s immune system is able to eradicate the residual malignancy immunologically.
The drawback to that therapeutic mechanism of action is that the donor cells can attack the recipient’s normal body. After all, while they may be HLA [human leukocyte antigen] matched, they’re not identical twins. This phenomenon or complication is called graft-vs-host disease. We’ve split up graft-vs-host disease into 2 types: 1 is acute and the other is chronic. Formerly, this was defined by timing after transplant. There was a 100-day timeline. With different conditioning regimens, donor types, and ability to do transplants with different platforms, the 100-day timeline no longer applies, and the different types are fully defined by clinical manifestations. Acute graft-vs-host disease still takes place within the first few months after transplant. It involves 3 organs, skin, gut, and liver. The skin is manifested by an erythematous skin rash. The gut is manifested by lower-GI [gastrointestinal] disease, causing diarrhea. There is an upper-GI variant, causing anorexia or persistent nausea. The liver is generally manifested by asymptomatic elevations in the liver function tests to start and is the rarest manifestation. Chronic graft-vs-host disease tends to occur after 3 to 6 months or later after transplantation. It’s a different disease. We believe they’re different immunological pathways that power acute and chronic graft-vs-host disease. The most common organ involved in chronic graft-vs-host disease are the skin, but the rash may be different. It’s generally not profound erythema but maybe appears eczematous. The eyes may become dry as well as the mouth, as a sort of sicca syndrome [Sjögren syndrome]. Chronic graft-vs-host disease can involve almost every organ in the body and is very heterogeneous. The 2 difficult manifestations we deal with include scleroderma, which involves the skin and the underlying fascia, or lung involvement as bronchiolitis obliterans. Chronic graft-vs-host disease tends to be less dramatic but also more long-lasting and oftentimes lifelong in terms of patients having to deal with the symptoms or us working with the patients in terms of lifelong management. Overall, they’re differentiated by the clinical manifestations, but there are certain patients who have characteristics of both and have overlap syndromes that have been well described.
Transcript Edited for Clarity