Graft-versus-host disease (GVHD) can develop as a complication of allogeneic stem cell transplant, a procedure sometimes used to treat leukemia or lymphoma. Transplanted donor cells can attack the recipient’s body and affect many parts of the body, including the liver, skin, and digestive system. Doctors use grading and staging systems to describe the severity and progression of GVHD.

In this article, we’ll cover how chronic and acute GVHD are staged and graded, as well as how stage and grade help doctors make decisions about treatment and prognosis.

Grading vs. Staging: What’s the Difference?

Grading and staging are two ways doctors measure how serious GVHD is, but they focus on different aspects. Grading looks at the overall impact of GVHD — how many organs are affected and how badly they’re damaged. Staging considers each organ separately, rating the severity of symptoms in specific areas like the skin, liver, or intestines to create a detailed map of the disease’s impact.

Acute vs. Chronic Graft-Versus-Host Disease Grading

GVHD grading depends on whether the disease is acute or chronic. In the past, acute GVHD was defined as developing within the first 100 days (about three months) after an allogeneic stem cell transplantation. Newer guidelines focus more on symptoms and severity than on timing. Acute GVHD mainly affects the skin, liver, and digestive system, whereas chronic GVHD appears after 100 days, involves more parts of the body, and can last a long time.

Staging Acute Graft-Versus-Host Disease

Staging for acute GVHD looks at each affected organ separately. Doctors assess the skin, liver, and gastrointestinal system to determine how severe the symptoms are in each area.

Skin Staging

Skin staging for acute GVHD depends mostly on how much body surface area is affected by the disease:

Stage 1 — Maculopapular rash (a rash with both flat and bumpy patches) covering less than 25 percent of the body

Stage 2 — Rash covering 25 percent to 50 percent of the body

Stage 3 — Widespread redness, peeling, and scaling that involves more than half of the body

Stage 4 — Large blisters on the skin

Liver Staging

Liver staging for acute GVHD is based on bilirubin levels in the blood. Bilirubin is a substance found in the bile, which is made by the liver. High bilirubin levels suggest the liver isn’t working properly. Doctors use the following stages to assess liver function, based on the amount of bilirubin:

• Stage 1 — 2 to 3 milligrams per deciliter
• Stage 2 — 3 to 6 milligrams per deciliter
• Stage 3 — 6 to 15 milligrams per deciliter
• Stage 4 — Above 15 milligrams per deciliter

Gastrointestinal Staging

Staging for gastrointestinal (GI) involvement in acute GVHD is based on how much diarrhea a person has each day:

• Stage 1 — At least half a liter
• Stage 2 — At least 1 liter
• Stage 3 — At least 1.5 liters
• Stage 4 — At least 2 liters or severe abdominal pain

People with stage 1 GVHD may need only topical treatments, such as steroid creams that are applied to the skin. More advanced stages (2 to 4) may also require systemic (whole-body) treatment, such as oral (taken by mouth) or injected steroids like methylprednisolone or prednisone. For steroid-refractory disease, in which symptoms don’t improve with steroids, doctors may prescribe other immunosuppressive medications instead.

Grading Acute Graft-Versus-Host Disease

After each organ or body system is assigned a stage, the values are combined to determine an overall grade. Acute GVHD is graded using either the Glucksberg scale or the International Bone Marrow Transplant Registry Severity Index. These grading systems assign an overall grade to categorize GVHD severity from mild to life-threatening:

• Grade 1 (mild) — Stage 1 or 2 skin involvement but no liver or GI involvement
• Grade 2 (moderate) — Stage 1 or 2 liver or GI involvement and stage 1, 2, or 3 skin involvement
• Grade 3 (severe) — Stage 2 or 3 skin, liver, or GI involvement
• Grade 4 (life-threatening) — Stage 4 skin, liver, or GI involvement

Staging Chronic Graft-Versus-Host Disease

Grading provides a broad picture of chronic GVHD’s overall severity, while staging breaks down the specific impact on individual organs. Staging involves assigning a score to each affected organ, ranging from 0 (no symptoms) to 3 (severe symptoms).

Staging criteria for each organ or part of the body are evaluated using the following scale:

• Stage 0 — No symptoms
• Stage 1 — Mild symptoms that are noticeable but manageable, like a mild rash or slightly dry eyes
• Stage 2 — Moderate symptoms affecting daily life, such as a rash covering 25 percent to 50 percent of the body or moderate dry mouth that requires treatment
• Stage 3 — Severe symptoms causing significant disability, like extensive scarring, severe GI issues, or lung problems like breathing trouble

Which Parts of the Body Are Staged With Chronic GVHD?

Staging helps pinpoint the most affected organs. For chronic GVHD, the following organs and body systems may be individually staged:

• Skin
• Mouth
• Eyes
• GI tract
• Liver
• Lungs
• Joints and fascia (connective tissue around muscles)
• Genital area

Staging each part separately helps your doctor create a treatment plan that prioritizes your most troublesome symptoms. Staging is also useful in assigning an overall grade to your disease.

Grading Chronic Graft-Versus-Host Disease

If you’ve been diagnosed with chronic GVHD, your doctor will assess how widespread and severe it is before deciding on treatment. Chronic GVHD is graded based on how severely it affects different organs and your ability to carry out daily activities.

Criteria for Grading Chronic GVHD

The National Institutes of Health (NIH) consensus criteria offer a standardized way to grade the severity of chronic GVHD. The system considers:

• Organs affected — Commonly involves the skin, liver, eyes, mouth, GI tract, lungs, joints, and fascia
• Symptoms — Includes both diagnostic symptoms and distinctive features that suggest GVHD but aren’t enough for diagnosis on their own
• Functional impact — Assesses how GVHD limits physical function and daily activities

Mild, Moderate, or Severe

Grading chronic GVHD helps doctors choose the right treatment and predict prognosis (outcomes). The classification system includes:

• Mild disease — Affects one or two organs with no significant functional impairment, such as mild dry eyes or minor skin changes
• Moderate disease — Involves at least three organs or causes moderate functional issues, like significant dry mouth or difficulty walking due to joint stiffness
• Severe disease — Leads to extensive organ involvement or serious functional impairment, such as severe lung restriction major or joint contractures

What Stage and Grade Mean for Prognosis and Treatment

The GVHD grade and stage help guide treatment options and predict outcomes. Lower grades and stages usually mean milder disease, which can often be managed with topical corticosteroids (steroids) or standard immunosuppressive therapies. If your symptoms improve, your doctor may slowly reduce your steroid dose.

Higher grades and stages indicate more severe organ involvement and a higher risk of complications. Treatment may include stronger immunosuppressants, biologics, or participation in a clinical trial. In chronic GVHD, more severe disease can mean longer-lasting symptoms and a greater impact on your quality of life, often requiring extended treatment.

It’s important to take medications as prescribed even if you start feeling better. If you have concerns about your treatment plan, talk to your hematology/oncology team (group of specialists who diagnose and treat blood disorders and cancer). Never stop or adjust your medicines without your doctor’s guidance.

Talk With Others Who Understand

On myGVHDteam, the site for people with graft-versus-host disease and their loved ones, people come together to ask questions, give advice, and share their stories with others who understand life with this condition.

Did you and your cancer care team discuss the grading and staging of GVHD? Share your experience in the comments below.