When you’re living with post-transplant graft-versus-host disease (GVHD), understanding which type you have is key to managing it. Although many people are familiar with acute GVHD and chronic GVHD, there’s also overlap syndrome — a mix of both. Overlap syndrome tends to hit harder at its onset and peak compared to chronic GVHD.

If you or a loved one has overlap syndrome, understanding the condition can help you make informed treatment decisions. Here are five facts to know about overlap syndrome.

1. Overlap Syndrome Is Linked to Both Acute and Chronic GVHD

Overlap syndrome occurs when a person has symptoms of both acute and chronic GVHD at the same time.

Acute GVHD usually affects the skin, liver, or gastrointestinal tract and typically appears within 100 days of an allogeneic stem cell transplant (or bone marrow transplant with donor cells). Persistent, recurrent, or late-onset acute GVHD appears after 100 days and has only acute symptoms, without signs of chronic GVHD.

Chronic GVHD often resembles autoimmune diseases and can happen anytime after a stem cell transplant but usually after 100 days. Symptoms vary widely and can affect one or multiple areas of the body, including the eyes, mouth, skin, nails, hair, gastrointestinal tract, lungs, liver, muscles, joints, and genitals.

If you have symptoms of both acute and chronic GVHD, you'll be diagnosed with overlap syndrome, which is considered a subtype of chronic GVHD.

2. Overlap Syndrome Affects the Body in Many Ways

Because overlap syndrome involves both acute and chronic GVHD symptoms, it can appear in a variety of ways.

The symptoms of acute GVHD may be easy to recognize:

• Skin symptoms — A maculopapular rash (flat, discolored spots with raised bumps) that may spread over the body, including the palms and soles, and may be mild or severe, with blistering and peeling
• Problems with liver function — Often detected through blood tests but sometimes showing up as jaundice (yellowing of the skin and eyes) or, in extreme cases, leading to confusion, bleeding, or fluid buildup in the abdomen
• Gastrointestinal symptoms — Most commonly severe diarrhea, sometimes along with nausea, vomiting, abdominal pain, and bleeding

Alongside acute GVHD symptoms, chronic GVHD symptoms may include:

• Dry eyes or vision problems
• Extremely dry mouth or mouth ulcers
• Dry skin or brittle nails
• Hair loss or dryness
• Weight loss
• Breathing trouble
• Muscle pain or joint stiffness
• Genital itching or irritation

Since GVHD symptoms can overlap with other conditions, your doctor will help you determine the cause and the best treatment plan.

3. Overlap Syndrome May Have an Impact on Outlook

Research shows that overlap syndrome is linked to worse outcomes compared to chronic GVHD alone. People with overlap syndrome tend to have significantly lower overall survival (how long a person lives after treatment) and shorter disease-free survival (the time without active disease).

A study across multiple hospitals found that people with overlap syndrome have lower survival rates both in the intensive care unit (ICU) and in the hospital overall. They’re often admitted to the ICU sooner after the transplant, suggesting a more aggressive disease course that progresses faster.

Although GVHD is serious, early diagnosis and treatment can help reduce complications and improve outcomes. It’s important to stay on top of your symptoms and talk to your doctor or transplant team anytime you have questions.

4. Overlap Syndrome Is Classified Based on Severity

Doctors classify overlap syndrome based on severity:

• Mild — Involves one or two affected organs, doesn’t affect the lungs, and doesn’t significantly affect daily life
• Moderate — Involves three or more organs, affects the lungs, moderately affects any organ or body system, or significantly affects daily function
• Severe — Moderately affects the lungs, significantly affects another organ or system, or causes dangerously low blood platelet counts

Your doctor will use a system to assess how much your affected organs are impacted over time. Blood tests, scans, and other exams may be needed to determine the severity of your overlap syndrome.

5. Treatment Varies Depending on Severity

Overlap syndrome is a form of chronic GVHD that also includes symptoms of acute GVHD. Treatment depends on its severity and which organs are affected.

For mild overlap syndrome, doctors often prescribe topical (applied to the skin) treatments for skin symptoms. If the skin isn’t affected, treatment focuses on the specific organ or system involved. However, if a rash covers more than half your body or symptoms are widespread, your doctor may instead recommend oral (taken by mouth) steroids or medications that suppress your immune system.

Moderate overlap syndrome is typically treated with an oral steroid, such as prednisone (Rayos). If additional treatment is needed for a specific organ or body system, the same medications used for mild overlap syndrome may be recommended.

For severe overlap syndrome, treatment usually includes oral steroids — similar to moderate cases — plus ruxolitinib (Jakafi), a medication that targets specific parts of the immune system that cause GVHD.

While you’re using corticosteroids and other immunosuppressive medications, your doctor will closely monitor you for side effects. These treatments can increase your risk of infection, so your doctor may also prescribe prophylaxis (preventive) medications to help reduce this risk.

Work With Your Doctor

If you’ve been diagnosed with overlap syndrome after a stem cell or bone marrow transplant, talk to your doctor or hematology team about your next steps. You’ll want to discuss your condition’s severity, affected organs, and any other risk factors. They might also tell you about ongoing clinical trials that could provide access to new and emerging treatments.

Managing GVHD can be emotionally challenging. Your doctor can connect you with mental health professionals, support groups, and counselors who understand chronic illness and can provide guidance. By working with your medical team, you can stay on top of all your symptoms, access the best available treatments, and get the support you need to improve your well-being and quality of life.

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.

Are you living with overlap syndrome? How does it affect your everyday life? Share your experience in the comments below.