Cancer; Transplant

Taking aim at graft-versus-host disease after stem cell transplant

Cancer; Transplant

Immune system defense
When the immune system senses foreign DNA from a stem cell transplant, it triggers a response and antibodies attack. The defense can cause symptoms from graft-versus-host-disease.

Most of the time, the immune system behaves like mild-mannered Bruce Banner, a gentle genius that goes about its business in the background, keeping us healthy by clearing away things that do not belong in our bodies, such as viruses, bacteria, parasites, and even cancer.

But when the immune system is triggered after a stem cell transplant, it sometimes becomes the Hulk, an uncontrollable monster smashing everything in its path whether it is dangerous or not. This is known as graft-versus-host disease (GVHD).

GVHD is a potentially serious complication that can occur after an allogeneic stem cell or bone marrow transplant. An allogeneic stem cell transplant is the transfer of another person’s immune system (donor) into a patient (recipient). In other words, donor stem cells from another person are transplanted into the patient, replacing a dysfunctional immune system. With GVHD, the donor stem cells (graft) attack the host because they see the host cells as a threat.

Mild “Hulking out” of the immune system is expected following an allogeneic transplant. It can be a sign the donor cells are doing their job and helping eliminate the blood cancer or immune disease that necessitated the transplant. Unmanaged GVHD can be life-threatening.

Stem cell transplants are safer than they have ever been. Here at UT Southwestern's Hematologic Malignancies and Cellular Therapy Program at Harold C. Simmons Comprehensive Cancer Center, we have performed more than 2,000 stem cell transplants and our survival rate for adult allogeneic stem cell transplants is the best in Texas.

Unfortunately, there is still a lot of outdated information floating around about GVHD, and we often talk with patients who are reluctant to get a stem cell transplant because of what they have read or heard. While it is uncommon to see life-threatening cases of GVHD these days, it is important to understand the signs of the disease, how we work to prevent it, and how we treat it when the immune system is triggered.

Who is at risk for GVHD?

Transplanting non-matching donor cells is the main risk factor for GVHD. So, the best chance to have a Bruce Banner outcome rather than a Hulk response is to get stem cells from a fully matched biological donor.

The risk of developing GVHD is estimated at 35%-45% for related donors and 60%-80% for non-related donors.

Potential donors are tested for human leukocyte antigens (HLA), tissue markers that tell the immune system which cells do and do not belong in your body. If we cannot find a related donor who is a full HLA match, the next best option is a fully matched unrelated donor. After that, we can consider a half-match donor, known as a haploidentical donor.

Diagram of allogenic bone marrow transplant

Our Hematologic Malignancies and Cellular Therapy Program team is evaluating a novel donor selection algorithm that could streamline the donor matching process. While more research is needed, early results have been promising, with fewer patients developing severe GVHD.

Other risk factors for GVHD include:

  • Advanced age of either the donor or recipient.
  • Donors who have been pregnant in the past, which exposes them to genetically different cells (alloimmunization).
  • Mismatched sex of the donor and patient, such as a male donor and female patient.
  • Myeloablative conditioning regimens.
  • Stem cells retrieved from peripheral blood rather than bone marrow.
  • Presence of cytomegalovirus and Epstein-Barr virus antibodies in the blood.

All patients who get a stem cell transplant at UT Southwestern will have GVHD prevention processes put in place to reduce their risk.

Symptoms of GVHD

There are two main types of graft-versus-host disease: acute and chronic. Symptoms can vary with each.

Acute GVHD usually develops within the first 100 days after a stem cell or bone marrow transplant. Symptoms can include:

  • Rash, itching, or redness of the skin
  • Jaundice, or yellowing of the skin and/or eyes
  • Abdominal pain or cramps
  • Diarrhea
  • Nausea and vomiting
  • Fever

Chronic GVHD usually starts more than three months after the transplant. Chronic symptoms are similar to those of acute GVHD and may also include:

  • Skin tightening or thickening
  • Dry mouth, mouth sores, gum disease
  • Dry eyes or vision changes
  • Fatigue
  • Hair loss
  • Shortness of breath
  • Muscle weakness
  • Joint pain or stiffness
  • Vaginal dryness, itchy penis, or pain with intercourse

Alert your transplant team immediately if symptoms develop. Prompt treatment can help limit the severity of GVHD. We use a GVHD grading system, with grade 1 being the least severe and grade 4 the most severe. The grade also helps us determine how to treat your GVHD.

Prevention and treatment of GVHD

We take every possible precaution to reduce the risk of graft-versus-host disease. Finding the best donor match is the crucial first step. Then, you will have conditioning therapy, which may consist of a combination of chemotherapy, radiation, and immunotherapy to remove abnormal cells from your blood and prepare your bone marrow to receive the new donor stem cells.

Graft versus host disease rash
Rash, itching, or redness of the skin are symptoms of acute GVHD.

We will prescribe preventive medicines to suppress your new immune system after the transplant to reduce the risk of GVHD and limit its severity.

Mild GVHD is limited to the skin and may need only a topical steroid cream to control it. Moderate symptoms may call for use of systemic steroids to suppress your immune system.

More complex or severe acute GVHD cases may require medications such as ruxolitinib, belumosudil, infliximab, basiliximab, abatacept or in the case of chronic GVHD use of ruxolitinib and belumosudil which calm immune cell activity in several ways. Recent clinical trial data has shown that the monoclonal antibody axatilimab may also successfully treat severe steroid-resistant GVHD. Light therapy (extracorporeal photopheresis, or ECP) may also curb swelling and inflammation through a combination of medication and ultraviolet light.

Depending on which organs are affected, you also may need treatment for:

  • Nausea
  • Diarrhea
  • Hair loss
  • Liver enzyme imbalance
  • Muscle and joint symptoms

What we are doing to prevent and treat GVHD

Great strides have been made in preventing and treating graft-versus-host disease, and we are working to further enhance stem cell and bone marrow transplant outcomes.

Innovative transplant process: We are pioneering alternative conditioning regimens designed to decrease toxicities and transplant related mortality.

Clinical trial: Patients will soon be able to enroll in a phase 3 clinical trial that will evaluate itolizumab, a new monoclonal antibody, as a way to manage severe GVHD. Earlier, smaller studies have shown itolizumab decreases the need for steroids and improves outcomes. Explore open clinical trials.

Team-based care planning: Our team is specially trained to care for patients with blood disorders and cancers. We meet regularly to discuss which type of treatment is best for every patient’s specific condition. For complex cases, we meet more frequently to track the patient’s progress and adjust to optimize their care. Watch a video about our collaborative care process.

Every patient receives a guide that walks you through the entire care process, introducing you to support services team members and specialists who will guide your care. Get the guide in English or Spanish.

GVHD may not be the hulking, catastrophic disease it was in the past, but in the rare cases that it is, we are prepared to help you fight it with a personalized plan that creates the best path toward positive outcomes.

To talk with a stem cell transplant expert, call 214-645-8300 or request an appointment online.