Graft-versus-Host Disease (GVHD) is a complication that can arise after an allogeneic stem cell transplant, a procedure used to treat certain blood cancers like leukemia. It occurs when immune cells from a donor (the graft) recognize the recipient’s body (the host) as foreign and begin to attack it. This reaction is a primary consideration for any patient undergoing this type of transplant. The donated cells create a new immune system for the patient, which is a powerful tool against cancer but also carries this risk.
The Transplant Connection to Leukemia
An allogeneic stem cell transplant, also known as a bone marrow transplant, is a treatment option for aggressive forms of leukemia. The process begins with the patient receiving high-dose chemotherapy, sometimes combined with radiation. The purpose of this step is to eliminate the patient’s existing bone marrow, which is where the cancerous leukemia cells originate.
Once the patient’s bone marrow has been cleared, they receive the transplant. Healthy, blood-forming stem cells are collected from a matched donor and infused into the patient’s bloodstream. These donor cells travel to the bone marrow, where they begin to engraft and produce new, healthy blood cells, including immune cells.
The establishment of this new immune system is the goal of the transplant. These donor-derived immune cells populate the body, taking over the function of protecting the patient from infections. This new system also provides a long-term defense against the leukemia returning.
The Double-Edged Sword of Donor Cells
The donor’s new immune cells have a dual role. Their negative potential is Graft-versus-Host Disease, which occurs when they identify the patient’s healthy tissues as foreign and launch an attack. This reaction is a direct result of genetic differences in human leukocyte antigen (HLA) markers between the donor and recipient.
GVHD is categorized into two forms: acute and chronic. Acute GVHD appears within the first 100 days post-transplant and targets the skin, liver, and gastrointestinal tract, causing rashes, jaundice, or digestive issues. Chronic GVHD develops later and can be more widespread, with symptoms that may include:
- Dry or gritty eyes
- A dry mouth
- Stiffness in the joints
- Changes to the skin or lungs
Conversely, the same immune response has a beneficial side known as the Graft-versus-Leukemia (GVL) effect. The donor’s T-cells, which cause GVHD, are also effective at eliminating any leukemia cells that survived chemotherapy. This GVL effect is a reason allogeneic transplants can be curative. A mild form of GVHD can be a positive sign that the new immune system is active, creating a balance between managing GVHD and preserving the GVL benefit.
Managing Graft-Versus-Host Disease
Medical teams manage GVHD starting with prevention. Before the transplant, patients begin a medication regimen to suppress the donor’s immune system, an approach called prophylaxis. Drugs like cyclosporine are used to dampen the new immune cells’ initial activity, giving them time to acclimate to the patient’s body.
If GVHD develops, the first line of treatment is corticosteroids, such as prednisone. These anti-inflammatory drugs are effective at calming the immune response that causes tissue damage in both acute and chronic forms. The goal is to reduce symptom severity and control the attack on the patient’s organs.
When GVHD does not respond to steroids, a condition known as steroid-refractory GVHD, doctors use other therapies. This includes a range of immunosuppressive medications that target different pathways of the immune system. The challenge is to suppress the harmful GVHD reaction while maintaining the helpful GVL effect.
Living with Chronic GVHD
Chronic GVHD can be a long-lasting condition requiring ongoing management. Patients work closely with their transplant team for regular monitoring to track symptoms and adjust treatments. This long-term follow-up helps manage the effects on various organs and catch new issues early.
Patients take an active role in managing their daily life with chronic GVHD. This includes diligent sun protection for sensitive skin and using moisturizers to combat dryness. Adhering to medication schedules is also necessary to keep the immune response under control and prevent flare-ups.
Supportive care is another component of living with chronic GVHD. This may involve physical therapy for joint stiffness or nutritional support for gastrointestinal issues. These therapies are aimed at alleviating symptoms and improving a person’s ability to perform daily activities.