For some people with aggressive leukemia (a cancer of the blood and bone marrow), an allogeneic hematopoietic stem cell transplant offers a potential cure. This procedure, also called an allogeneic bone marrow transplant, replaces diseased blood-forming stem cells with healthy ones from a donor.

However, this life-saving treatment comes with risks. One major complication is graft-versus-host disease (GVHD), which happens when the donor’s immune cells see the recipient’s body as foreign and attack healthy tissues.

In this article, we’ll explain how an allogeneic stem cell transplant works, the differences between acute and chronic GVHD, and the risk factors that make GVHD more likely. We’ll also cover ways to reduce your risk and manage this complication if it develops.

How Stem Cell Transplants Treat Leukemia

An allogeneic stem cell transplant may be recommended for people with aggressive blood cancers including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and cases of chronic lymphocytic leukemia (CLL) that are difficult to treat.

If standard treatments like chemotherapy or targeted therapy can’t fully eliminate leukemia, an allogeneic stem cell transplant may offer another option. This procedure replaces a person’s diseased bone marrow with healthy blood-forming stem cells from a donor.

Before the transplant, the cancerous bone marrow must be destroyed to make room for the new cells. This is typically done with high-dose chemotherapy — sometimes combined with total body irradiation — to kill remaining cancer cells and weaken the immune system. Weakening the immune system reduces the risk that it will attack the donor cells, helping the transplant succeed.

Graft-Versus-Leukemia Effect

The graft-versus-leukemia (GVL) effect is a critical part of a successful allogeneic stem cell transplant. This effect happens when donor T cells — a type of immune cell that kills infected or cancerous cells — identify and destroy any remaining leukemia cells.

This immune response helps prevent the leukemia from coming back, making GVL an important benefit of the transplant. However, the same donor T cells that attack cancer cells can also mistake healthy tissues — like the gastrointestinal tract, skin, and liver — for foreign invaders. When this happens, it leads to GVHD, a serious complication that can cause inflammation and organ damage.

How Does GVHD Develop After a Stem Cell Transplant?

GVHD happens when the donor T cells identify the recipient’s healthy cells as foreign and attack them. There are two main types of GVHD, acute and chronic.

Acute GVHD

Acute GVHD typically develops within the first 100 days (about three months) after a transplant. It’s most likely to affect the skin, liver, or gastrointestinal tract, leading to symptoms like rashes, jaundice (yellowing of the skin and eyes), diarrhea, or ulcers (painful, open wounds).

Acute GVHD can range from mild to severe. In some cases, it can be life-threatening — more than 10 percent of people who receive a hematopoietic stem cell transplant die from GVHD-related complications​.

Chronic GVHD

Chronic GVHD is the most common complication of an allogeneic hematopoietic stem cell transplantation. It develops after the first three months post-transplant, usually within the first year. However, 5 percent to 10 percent of people don’t develop signs and symptoms until later. Unlike acute GVHD, chronic GVHD can impact nearly any tissue or organ in the body, including the eyes, lungs, joints, and genitals. Symptoms are wide-ranging but can include shortness of breath, joint stiffness, dry mouth, and dry eyes.

Overlap Syndrome

Sometimes, symptoms of acute GVHD can show up after the first three months. This is called persistent, recurrent, or late-onset acute GVHD. In other cases, features of both acute and chronic GVHD develop at the same time, a condition known as overlap syndrome.

Is GVHD Ever a Good Sign for Leukemia Treatment?

Mild GVHD can actually be a sign that the transplant is working, as it shows that donor T cells are attacking leukemia cells along with foreign tissues. This is part of the GVL effect. However, severe GVHD can cause serious, even life-threatening complications.

If you experience any new or worsening symptoms after a transplant, contact your healthcare team immediately. Early treatment can help manage GVHD and improve outcomes​.

Risk Factors for GVHD

The risk of GVHD varies from person to person, but certain factors can make it more likely.

The Role of Donor HLA Match

One of the most important factors affecting GVHD is how closely the human leukocyte antigen (HLA) markers between donor and recipient match.

HLAs are proteins on the surface of most cells in the body. They act like ID tags for the immune system. They help the body recognize its own cells and attack foreign invaders like viruses or bacteria. When a donor’s HLA markers closely match the recipient’s, the transplanted immune cells are less likely to see the recipient’s healthy tissues as foreign and attack them.

However, if there’s an HLA mismatch, the risk of GVHD increases significantly. That’s why doctors use tissue typing tests to carefully match donors and recipients. A sibling or close relative with a closely matched HLA type is ideal, but unrelated donors can also be used if they’re a good match. Even with a perfect match, there’s still some risk of GVHD because of minor differences in other immune system proteins​.

What Else Raises the Risk for GVHD?

Other factors also influence the likelihood of GVHD. For one, the source of stem cells plays a role. Peripheral blood stem cells — stem cells collected from a donor’s bloodstream — carry a higher risk of GVHD compared to stem cells from bone marrow or cord blood (blood from a baby’s umbilical cord).

Additionally, unrelated donor transplants tend to carry a higher risk of GVHD than matched siblings. Researchers think this is because of subtle genetic differences. The age of the donor and recipient is an important factor, too. Older individuals — whether donating or receiving — tend to carry a higher risk of the recipient developing GVHD. Researchers believe this is due to changes in immune system function with age.

Strategies To Reduce the Risk of GVHD

Understanding GVHD risk factors allows doctors to take steps to lower the chances of this complication after an allogeneic stem cell transplant for leukemia. One of the most effective ways to prevent GVHD is using immunosuppressive medications, which help stop the donor’s immune cells from attacking the recipient’s healthy tissues.

Doctors often prescribe a combination of immunosuppressive and chemotherapy drugs to reduce GVHD risk. Some commonly used medications include:

• Cyclophosphamide
• Cyclosporine (Neoral)
• Tacrolimus (Prograf)
• Methotrexate (Trexall)

In some cases, corticosteroids (steroids) are prescribed to further suppress the immune system and reduce inflammation. These medications can be used to prevent GVHD or treat existing GVHD. Common examples include methylprednisolone and prednisone. They may be given intravenously (an injection into a vein) or taken as pills.

Although these medications help reduce GVHD risk, they can have side effects, including an increased risk of infections. That’s why transplant teams closely monitor GVHD recipients and adjust treatments as needed​.

How Common Is GVHD After a Stem Cell Transplant for Leukemia?

Researchers estimate that about 30 percent to 70 percent of people who receive a stem cell transplant experience acute GVHD, and about 40 percent to 50 percent of people develop chronic GVHD. The likelihood that a recipient will get GVHD depends on factors like donor type, stem cell source, and personal characteristics like age.

Balancing the Risks and Benefits of Stem Cell Transplants

Choosing to undergo a stem cell transplant is a deeply personal decision. The risks of GVHD, infection, and other complications must be weighed against the potential for curing leukemia. For some people — especially those with high-risk blood cancers — an allogeneic stem cell transplant may offer the best chance of survival.

However, not everyone is eligible for the procedure, due to the higher risk of severe side effects and complications of the procedure. Factors like age, overall health, and the specific type of leukemia are important considerations.

For those who can’t tolerate high doses of chemotherapy, a reduced-intensity stem cell transplantation might be an option. This approach still allows donor stem cells to replace diseased bone marrow, but it uses lower doses of chemotherapy and radiation, making it easier on the body​.

Making treatment decisions should be a collaborative process between you, your family, and your hematology/oncology care team. Be open about your treatment goals, concerns, and quality-of-life priorities. Together, you can determine the best course of action based on your specific medical needs​.

Life After a Stem Cell Transplant

Recovery after a stem cell transplant requires ongoing medical care to monitor for complications like GVHD, infections, or relapse (when cancer comes back). Regular follow-up appointments allow your doctor to track your progress and adjust your treatment as needed.

Many people need long-term immunosuppressive medications to prevent GVHD and supportive therapies to manage side effects. These may include:

• Antiviral and antifungal medications to lower infection risk
• Physical therapy to regain strength and mobility
• Dietary support to manage nutrition and digestive issues​

Living with GVHD can be challenging, but support networks and advocacy groups can offer guidance, resources, and a sense of community. Connecting with others who have been through similar experiences can help improve mental and emotional well-being.

If you or a loved one is considering a stem cell transplant, there are many resources available to help navigate every step of the journey — from preparing for treatment to adjusting to life after transplant​.

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 the condition.

Have you or a loved one undergone a stem cell transplant for leukemia? How long after your transplant did you develop GVHD? Share your experience in the comments below.