Chronic Graft-Versus-Host Disease - Types and Treatment

Creator: Dr. Lakshika Sree. K. V.
Published: 2023-02-08T18:35:24

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Chronic graft versus host disease refers to the severe complication that arises after organ transplantation. Read further to know about its management.

Written by

Dr. Lakshika Sree. K. V.

Medically reviewed by

Dr. Kaushal Bhavsar

February 8, 2023

January 3, 2024

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Contents

What Are the Types of Graft Versus Host Disease?
What Is Chronic Graft Versus Host Disease?
How Does a Graft Versus Host Disease Develop?
What Are the Symptoms of Chronic Graft Versus Host Disease?
Who Are More Prone to Develop Chronic Graft Versus Host Disease?
How to Diagnose a Graft Versus Host Disease?
What Is the Treatment for Chronic Graft Versus Host Disease?

Introduction:

Graft versus host disease (GvHD) is a reaction that occurs after allogeneic transplantation. Allogenic transplantation is a transplant of cells, tissues, or organs from a donor of the same species but not genetically identical. The transplanted organ or cell appears as a foreign body to the patient receiving the transplant and tries to show rejection reactions. Graft versus host disease usually occurs after a bone marrow or stem cell transplant. These patients develop a life-threatening complication that needs immediate hospitalization.

What Are the Types of Graft Versus Host Disease?

The graft versus host disease is divided into the following types depending on the time the clinical features start.

Acute Graft Versus Host Disease: Occurs 10 to 100 days after the transplant. About 50 percent of the patients receiving an allotransplant are affected.
Persistent, Recurrent, or Late-Onset Acute Graft Versus Host Disease: Same as the acute GvHD, but the reactions occur after 100 days.
Chronic Graft Versus Host Disease: Occurs 90 to 600 days after the transplant. About 6 to 80 percent of the individuals are affected.
Overlap Syndrome: This condition combines the features of both acute and chronic GvHD. It can occur at any time post the transplantation.

What Is Chronic Graft Versus Host Disease?

Chronic GvHD is one of the main complications that leads to major medical consequences and even death of the patient. It affects a single organ or several organs, causing symptoms related to the mouth, skin, nails, hair, muscles, joints, lungs, liver, and genital organs. Most of them affected with chronic GvHD have mild to moderate symptoms. Severe symptoms are noticed in only about 10 to 15 percent of the patients. The treatment for these patients is of a longer duration and lasts up to three to five years. In rare situations, lifelong treatment may also be required.

What Is Acute Graft Versus Host Disease?

Acute GvHD takes place 100 days after the transplantation and affects the skin, gastrointestinal tract, or liver. The following are the symptoms of acute GvHD:

Skin rash on the palm, soles, upper body, and other extremities. Blisters may start forming on the rash, and the exposed skin sometimes flakes off in severe cases.
Abdominal cramps, nausea, vomiting, diarrhea, and loss of appetite are present when the gastrointestinal tract is involved.
If the liver is affected, the patient has yellowish discoloration of the eyes or skin due to jaundice. The liver function tests also show abnormal levels.

The individuals more prone to develop acute GvHD are those who have received a transplant from a mismatched donor, a female donor who was pregnant previously and an increased age of the donor or the recipient.

How Does a Graft Versus Host Disease Develop?

In all transplantation cases, there is a recipient and a donor. The one who receives the transplant is the recipient, and the donor is the person who donates the transplant. When the graft contains stem cells or tissues, they see the cells within the body as foreign agents and start to attack them. This is because of the mismatch of the human leukocyte antigen (genes that help code proteins to differentiate one person from another). Hence, HLA (human leukocyte antigen) matching between the donor and the recipient must be done before transplantation to prevent unfavorable consequences.

What Are the Symptoms of Chronic Graft Versus Host Disease?

Depending on the part that gets affected, the symptoms may vary. If multiple organs are affected, the symptoms specific to all those organs will be present.

Oral Symptoms:
Dryness of the mouth.
Sensitivity to hot, cold, and spicy food.
Tooth decay and gum diseases.
Difficulty in swallowing.
Formation of ulcers in the mouth and throat that are painful and cause a burning sensation.
Skin:

Skin rash.
Skin becomes dry and itchy.
Skin discoloration.
The skin becomes thick and tight, leading to restricted joint movement.
The sweat gland in the skin gets damaged; hence the skin becomes intolerable to temperature changes.
Nails:

Brittle nails.
Change in the texture of nails.
Loss of nails.
Hair:

Hair loss on the scalp and body.
Premature graying of hair.
Gastrointestinal Tract:

Nausea, vomiting, diarrhea.
Unexplained weight loss.
Loss of appetite.
Abdominal pain.
Lungs:

Difficulty in breathing.
Persistent cough.
Wheezing.
Liver:

Swelling in the abdominal region.
Symptoms of jaundice.
Abnormal levels in liver function test.
Muscle and Joints:

Weakness of the muscle.
Muscle cramps.
Stiffness of the joints.
Genitalia:

In females, symptoms related to the vagina are present. Dryness, itching, ulceration, and pain in the vaginal region. There is intense pain during sexual intercourse.
In males, irritation, itching, and scarring of the penis are present, causing discomfort while urinating.

The patient most commonly experiences skin, mouth, nails, and liver symptoms. Rarely do the eyes get affected, causing dry eyes. Eye involvement is an indicator of a severe form of chronic GvHD and leads to a poor outcome.

Who Are More Prone to Develop Chronic Graft Versus Host Disease?

The following conditions make an individual more susceptible to developing chronic graft versus host disease:

Older age group.
Previous history of graft rejection reactions.
When the patient is transplanted with cells from a donor that are not matching.
When the cells are transplanted from the bloodstream rather than the bone marrow or the spinal cord.
When a male patient receives cells from a female donor.
When a male or a female gets cells from a female donor who was pregnant previously.

How to Diagnose a Graft Versus Host Disease?

The doctor runs a few laboratory and imaging tests to identify the presence of graft versus host disease correctly.

Liver Function Test: A blood test to identify liver damage by identifying the liver enzyme levels in the body.
Imaging Tests: X-ray of the abdomen, CT (computed tomography) scan of the abdomen and chest, MRI (magnetic resonance imaging) scan, PET (positron emission tomography) scan, and endoscopy (a flexible tube with a camera attached at one end to visualize the inner structures in detail from the outside).
Biopsy: A biopsy can also be performed wherein a sample tissue is collected from the patient and examined in detail under a microscope.

What Is the Treatment for Chronic Graft Versus Host Disease?

The treatment for chronic GvHD depends on the organ affected and the symptoms that the patient experiences. The doctor prescribes creams or ointments for the rash, hair and nail loss treatment, drugs to control gastric symptoms, physical therapy for muscles, and other symptomatic treatment.
Symptomatic treatment is initially started to control the symptoms; if they fail, the doctor prescribes medicines that depress the immune system. The drugs that suppress the immune system are Prednisone, Cyclosporine, Tacrolimus, or Sirolimus. Prednisone effectively decreases the immune response when used alone or in combination with Cyclosporine and Tacrolimus. The other effective drugs include:
- Oral or intravenous infusion of steroids.
- Ibrutinib is a drug that affects the immune system.
- Ruxolitinib is a drug that suppresses immunity and the inflammatory process.
- Belumosudil is a drug that decreases inflammation and scarring.
The entire treatment takes about three to five years or longer, depending on the patient’s condition and their progress towards the treatment. The patient must be monitored regularly and prevent further complications.

Conclusion:

Chronic graft versus host disease is an adverse reaction that occurs 100 days after placing a transplant. The symptoms of graft rejection reactions, if noted, must be brought to the doctor’s notice immediately. If left untreated, it may lead to the death of the individual. So, all transplantation procedures must be done with the utmost care by matching the human leukocyte antigen between the donor and the recipient for a successful transplant without developing complications postoperatively.

Frequently Asked Questions

1. What Is Chronic Graft Versus Host Disease?

Chronic graft versus host disease is a life-threatening complication. This can occur after a bone marrow or stem cell transplant. It happens when the transplanted cells attack the recipient's healthy tissues and organs, leading to a range of symptoms, including skin rash, dry eyes, mouth sores, and lung or liver problems. Effective management and treatment of cGVHD require a multidisciplinary approach.

2. What Is the Difference Between Chronic vs. Acute Graft Versus Host Disease?

cGVHD develops gradually after a bone marrow or stem cell transplant, and its symptoms can last for a prolonged period of time. Acute graft versus host disease (aGVHD), on the other hand, typically appears within the first few weeks after the transplant and has a more sudden onset. While both conditions involve the transplanted cells attacking the recipient's healthy tissues, their timing, duration, and severity differ.

3. Does Chronic GVHD Go Away?

Chronic graft versus host disease (cGVHD) may not completely go away, but its symptoms can be managed and improved with proper treatment. Treatment may include medications to suppress the immune system, targeted therapies, and supportive care to address specific symptoms. Working and monitoring for any potential complications can help.

4. What Is the Most Common Organ Affected by GVHD?

The skin is the most commonly affected organ in this disease, with up to 80 % of patients experiencing some degree of skin involvement. Other commonly affected organs include the liver, gastrointestinal tract, lungs, and eyes. The severity and extent of organ involvement can vary widely between patients and depend on a range of factors, such as the type of transplant, donor characteristics, and the recipient's health status.

5. What Is the First Line Treatment for GVHD?

Corticosteroids such as Prednisone are often the first-line treatment for (GVHD) due to their potent anti-inflammatory and immunosuppressive effects. These medications can help reduce inflammation and prevent the immune system from attacking the recipient's healthy tissues. In some cases, other immunosuppressive drugs or targeted therapies may be used in combination with corticosteroids for more severe or refractory cases of GVHD.

6. What Is Chronic Graft Versus Host Disease in Kidney Transplantation?

cGVHD is a rare but serious complication that can occur in kidney transplant recipients, usually in the setting of a simultaneous bone marrow or stem cell transplant. It is characterized by the transplanted immune cells attacking the recipient's healthy tissues, leading to a range of symptoms, including skin rash, joint pain, dry mouth and eyes, and liver or lung dysfunction. Effective management and treatment of cGVHD in kidney transplant recipients require a multidisciplinary approach.

7. What Is Chronic Graft Versus Host Disease Children?

Chronic graft versus host disease (cGVHD) can occur in children who have undergone a stem cell or bone marrow transplant, particularly if the donor is a relative or unrelated adult. Children with cGVHD may experience symptoms such as skin rash, oral ulcers, joint pain, and liver or lung dysfunction, which can affect their quality of life and overall health. Treatment for cGVHD in children involves a combination of immunosuppressive medications, targeted therapies, and supportive care to manage symptoms and prevent complications.

8. Is Acute or Chronic GVHD Worse?

The severity and prognosis of aGVHD and cGVHD depend on various factors, such as the type of transplant, the donor-recipient match, and the extent of organ involvement. While aGVHD typically has a more sudden onset and can be life-threatening, cGVHD can last for a prolonged period of time and affect multiple organs. Both conditions require prompt and effective management.

9. What Is the Latest Treatment for GVHD?

There are several promising new treatments for GVHD that are currently being studied in clinical trials, including novel immunosuppressive drugs, cellular therapies, and targeted therapies. Some examples include JAK inhibitors, CAR-T cell therapy, and mesenchymal stem cell therapy. They tend to show the potential to improve outcomes.

10. What Is the New Drug for Chronic GVHD?

Several new drugs are being studied for the treatment of cGVHD, including ruxolitinib, which is a JAK inhibitor that has shown promising results in clinical trials. Ruxolitinib works by blocking the activity of certain enzymes involved in immune cell signaling, leading to a reduction in inflammation and tissue damage. It is currently approved by the FDA for the treatment of myelofibrosis and polycythemia vera, and ongoing studies are investigating its efficacy and safety in cGVHD patients.

11. What Causes Death in GVHD?

Death in GVHD can occur due to a range of factors, such as infection, organ failure, and the development of secondary malignancies. GVHD can weaken the immune system and make patients more susceptible to infections, particularly in the setting of immunosuppressive treatment. Moreover, severe and uncontrolled GVHD can lead to damage to vital organs such as the liver, lungs, and gastrointestinal tract, which can be life-threatening.

12. What Is the Survival Rate of Chronic Graft Versus Host Disease?

The survival rate of cGVHD varies depending on various factors such as the severity and extent of organ involvement, age and overall health status of the patient, and response to treatment. Studies have shown that the 5-year survival rate of cGVHD patients ranges from 50 % to 80 %, with better outcomes reported in those who achieve a complete or partial response to treatment. However, long-term complications such as secondary malignancies and chronic organ dysfunction may impact overall survival and quality of life.

13. Is Chronic Graft Versus Host Disease Rare?

The estimated incidence of cGVHD is 30 to 70 % among transplant recipients. While acute GVHD is more common in the immediate post-transplant period. cGVHD can occur months to years after the transplant and affect multiple organs.

14. How Long Is Treatment for GVHD?

The duration of treatment for Graft Versus Host Disease (GVHD) depends on several factors, such as the type and severity of GVHD, response to treatment, and the presence of complications. While some patients may require only a short course of treatment with immunosuppressive medications, others may need long-term or even lifelong treatment to control symptoms and prevent disease recurrence.

15. What Foods to Avoid With GVHD?

Patients with Graft Versus Host Disease (GVHD) may need to avoid certain foods that can exacerbate symptoms and increase the risk of infection, such as raw or undercooked meats and seafood, unpasteurized dairy products, and raw fruits and vegetables. Additionally, spicy, acidic, or high-fiber foods may irritate the gastrointestinal tract and worsen digestive symptoms. A dietitian or healthcare provider can help develop an individualized nutrition plan that meets the specific needs of GVHD patients.

16. How Do Steroids Treat GVHD?

Steroids are commonly used in the treatment of Graft Versus Host Disease (GVHD) due to their potent anti-inflammatory and immunosuppressive effects. Steroids work by binding to and inhibiting the activity of certain enzymes involved in immune cell signaling, thereby reducing inflammation and tissue damage. While steroids can be effective in controlling GVHD symptoms, they can also cause significant side effects, such as the increased risk of infection, fluid retention, and long-term use can cause bone loss.

Sources

Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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