What are the different types of GvHD?

There are two distinct forms of graft-versus-host disease (GvHD), acute and chronic.

Acute GvHD

Acute GvHD typically presents after the transplant of the donor cells and may manifest in the skin, gastrointestinal (GI) tract, and/or liver. Organ-specific manifestations are as follows:

• Skin: Rash described as measles-like, which may or may not be itchy
• GI tract: Upper GI tract symptoms of persistent nausea, vomiting, or poor oral intake, and/or a lower GI tract symptom of diarrhea (diarrhea due to acute GvHD is typically watery, does not respond to anti-diarrheal medications, and happens regardless of eating; it will persist even when fasting)
• Liver: Laboratory evidence of an increase in liver chemicals, including bilirubin, alkaline phosphatase, or liver enzymes (AST or ALT)

How is acute GvHD graded?

Each of the above organs is staged from 0 (no involvement) to 4 (severe involvement) based on the extent of symptoms. The GI tract is divided into the upper GI tract and lower GI tract, with the upper GI tract only given a score of 0 (no involvement) or 1 (symptoms attributable to GvHD). Based on the above organs, an overall acute GvHD grade of 0 to IV is assigned, with Grade III or IV indicating more severe and life-threatening manifestations.

When are you at most risk for acute GvHD?

The majority of acute GvHD cases typically occur within the first 100 days following the transplant. Acute GvHD can also occur beyond 100 days, especially when immunosuppressive drugs are being tapered or stopped. The presence of acute GvHD manifestations beyond 100 days is typically referred to as late acute GvHD.

Chronic GvHD

The first signs or symptoms of chronic GvHD typically appear at roughly 6 months following the transplant; however, symptoms can appear earlier or later. Often, the first sign of chronic GvHD occurs after a patient has returned to their home community and may be seeing their transplant providers on a less regular basis. As such, it is important for all patients to be aware of the most common symptoms of chronic GvHD so they can alert their transplant team.

Chronic GvHD can have many different manifestations, but it often resembles autoimmune conditions, which occur in the non-transplant population. The eight most common organs that may be affected by chronic GvHD include the eyes, mouth, skin, GI tract, liver, joints, lungs, and genitals.

How is chronic GvHD graded?

Each of the above organs is scored from 0 (no involvement) to 3 (severe involvement) based on how severe the individual organs are impacted and/or the severity of the symptoms. Depending on the number of organs or which organs are involved and how severely they are impacted, patients are given an overall chronic GvHD grade of mild, moderate, or severe.

A patient is categorized as having mild chronic GvHD when they have no more than 2 organs involved with mild (score of 1) severity. Patients are categorized as having moderate chronic GvHD if they have more than two organs involved or a single organ with moderate (score of 2) impairment. Patients are considered to have severe chronic GvHD by the presence of at least one organ with severe (score of 3) involvement. Because lung GvHD is considered a more life-threatening form of chronic GvHD, patients with lung involvement are considered to have moderate or severe chronic GvHD.

What is the significance of the chronic GvHD grade?

Often, patients with mild chronic GvHD will not require treatment beyond monitoring and supportive therapies such as topical agents. Most patients with moderate to severe chronic GvHD will require a form of systemic therapy.

Can you be diagnosed with both types of GvHD?

A diagnosis of acute GvHD is a risk factor for later development of chronic GvHD. Additionally, it is possible to have concurrent manifestations of acute and chronic GvHD, which is referred to as overlap syndrome.

References

1. Justiz Vaillant AA, Modi P, Mohammadi O. Graft-versus-host disease. In: StatPearls. StatPearls Publishing; 2024. http://www.ncbi.nlm.nih.gov/books/NBK538235/. Accessed Dec 14, 2024.
2. Types and grades of GvHD. Cancer Research UK. https://www.cancerresearchuk.org/about-cancer/coping/physically/gvhd/types-grades. Accessed Dec 14, 2024.
3. Rowlings PA, Przepiorka D, Klein JP, et al. IBMTR Severity Index for grading acute graft-versus-host disease: Retrospective comparison with Glucksberg grade. Br J Haematol. 1997;97(4):855-864. DOI: 1046/j.1365-2141.1997.1112925.x.
4. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1. DOI: 10.1016/j.bbmt.2014.12.001.