Acute vs Chronic GVHD: Identification and Stratification

Insight on the identification of acute versus chronic graft-versus-host disease, including best diagnostic and risk stratification practices.


Corey Cutler, MD, MPH, FRCPC: Acute and chronic graft-versus-host disease [GVHD] are extremely different scenarios. Acute and chronic GVHD are clinical syndromes and we diagnose them based on the clinical presentation of the patient, but they differ from a biologic point of view as well. Acute graft-versus-host disease is largely thought to be a T-cell mediated disorder and presents with involvement of 3 organs, the skin, the gastrointestinal tract, and the liver. Chronic graft-versus-host disease is a biologically heterogeneous process that involves many different cell lines, including B cells, T cells, monocytes and macrophages, and other effector cells. Chronic GVHD is also more heterogeneous in terms of its clinical presentation. It can affect any organ system, although the skin, mouth, eyes, and the myofascial tissues are the most affected. The interesting thing about chronic GVHD, is that patients tend not to develop disease in all the possible organ systems but only a select few. Two patients with chronic graft-versus-host disease might have entirely separate or different manifestations, whereas all patients with acute GVHD will have manifestations in 1 or more of 3 organs only. There’s much more overlap in terms of the clinical presentation of acute than there is of chronic GVHD.

Chronic GVHD is diagnosed largely based on clinical grounds. We tend not to use histologic or biopsy confirmation of involved organs. For the most part, chronic GVHD is recognizable by a transplant physician. Some organs require a biopsy, for example, the intestinal tract or liver. This is usually done to exclude other diagnostic possibilities, such as infection in the esophagus or in the gastrointestinal tract, or a drug toxicity in the liver. However, most of us don’t use biopsy unless there is a clinical question whether there could be something other than chronic GVHD. Many of our patients present to other physicians and other specialists who might recognize the clinical manifestations of chronic GVHD as an autoimmune condition involving that organ system. The challenge is ensuring that our patients are aware that they should be coming to us first with new signs or symptoms, rather than going to a sub-specialist like a rheumatologist who might diagnose a joint or muscle problem as something like rheumatoid arthritis. The treatments are largely similar, but we have a slightly different approach to alloimmune diseases like GVHD as compared to autoimmune diseases like rheumatoid arthritis.

Chronic GVHD is staged rather straightforwardly using the NIH [National Institutes of Health] chronic GVHD staging system. This divides patients into 3 broad categories: mild, moderate, or severe chronic GVHD. [It’s] based on the number of organs that are involved and the severity of the individual organ involvement. The staging system for chronic GVHD is simpler than the staging systems for acute graft-versus-host disease. We generally recognize that moderate and severe chronic GVHD require systemic therapy because the number of organs involved or the degree of organ involvement is too high to treat only topically. Whereas patients with mild chronic GVHD can often be managed with organ-specific topical type therapies.

Transcript edited for clarity.

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