What is Graft Versus Host Disease?

Graft-versus-host disease (GVHD) is caused by a series of "cytokine storms" stimulated by T lymphocytes in allogeneic donor grafts after transplantation. Target cells are used to initiate cytotoxic attacks, of which skin, liver and intestine are the main target targets. The incidence of acute graft-versus-host disease is 30% to 45%, and the incidence of chronic is lower than acute.

Basic Information

English name

graft versus-host disease

Visiting department

Hematology

Common causes

T lymphocytes in allogeneic donor grafts after transplantation, launching cytotoxic attack on recipient target cells

Common symptoms

Skin congestion and maculopapular rash, refractory diarrhea

Causes of graft-versus-host disease

After transplantation, the T lymphocytes in the allogeneic donor grafts are targeted by the recipient's target cells to cause cytotoxic attack. The more mismatched donor and recipient HLA-matching sites, the greater the possibility of severe graft-versus-host disease; women who have undergone pregnancy or who have been pregnant multiple times are sensitized by fetal alloantigen stimulation during pregnancy The grafts they provide are prone to induce graft-versus-host disease. The older they are, the higher the incidence and severity of the disease; repeated blood transfusions before transplantation can increase the risk of graft-versus-host disease; recipients develop viral infections. For example, infections such as cytomegalovirus, shingles virus, and varicella-zoster virus can increase the incidence of graft-versus-host disease, as do donors with viral infections.

Clinical manifestations of graft versus host disease

According to the time when graft-versus-host disease occurs after transplantation, those who occur within 100 days are called acute graft-versus-host disease, and those who occur after 100 days are called chronic graft-versus-host disease.

Acute graft versus host disease

It occurs in the early post-transplant period and is one of the important complications of early post-transplant death. It mainly affects the skin, gastrointestinal tract, and liver, and in a few cases can also affect other organs. The skin is the most commonly affected organ, mainly manifested as skin congestion and maculopapular rash, which can be accompanied by itching and pain. It first appeared in the palms, soles of the feet, and then extended to the cheeks, ears, neck, torso, and back of the chest. In severe cases, there was epidermal necrosis and skin exfoliation. Gastrointestinal involvement is mainly manifested as refractory diarrhea, with daily defecation volume of more than 1000 ml, accompanied by anorexia, nausea, and vomiting. In severe cases, intestinal colic, blood in the stool, and intestinal obstruction occur. Liver lesions often appear last, with jaundice, elevated serum bilirubin, and alkaline phosphatase. Acute graft-versus-host disease occurs mostly 20 to 40 days after transplantation.

Clinically, the severity of the affected organs is divided into , , , and degrees (or grades). Skin involvement is usually not life-threatening, such as visceral involvement, severe jaundice, refractory diarrhea and bloody stools, intestinal colic, and severe systemic symptoms have a poor prognosis.

2. Chronic graft versus host disease

Occurs 100 days to one and a half years after transplantation. A small number of patients can occur 2 years after transplantation. The incidence varies with the source of the graft, ranging from 20% to 70%. Among them, 20% to 40% are lethal graft-versus-host disease, which is an important factor affecting the long-term survival and quality of life of allogeneic hematopoietic stem cell transplantation. Chronic graft-versus-host disease is related to the above-mentioned susceptibility factors. For example, if the graft is derived from the donor's peripheral blood, the incidence of non-marrow will increase, because there may be more active immune cells in the peripheral blood than the bone marrow. In addition, patients with previous acute graft-versus-host disease are also prone to chronic graft-versus-host disease. Post-transplantation due to implantation failure or leukemia recurrence, peripheral blood lymphocyte infusion from the same donor is also a risk factor for chronic graft-versus-host disease.

Chronic graft-versus-host disease often affects the oral mucosa. Dry mouth is the earliest and most common sign. It can also be accompanied by oral pain or lichenification of the oral mucosa. In the early stage of skin involvement, lichen planus-like skin lesions may appear, and polygonal papules may appear. In severe cases, generalized skin lesions are present. Late-stage skin becomes darker, atrophy and fibrosis, similar to scleroderma, and can affect joint activity and cause joint contracture distortion. Eye involvement is manifested as dry eye and tears are significantly reduced. Liver involvement is more common, mainly as jaundice, and pathologically as liver necrosis or cirrhosis. Gastrointestinal spread is also very common. Esophageal lesions can cause swallowing difficulties and pain. If they affect eating, they can cause weight loss. Barium meal imaging of the esophagus shows a cone-shaped change in the esophagus. In addition, chronic graft-versus-host disease can affect the bronchi and lungs, resulting in reduced lung function and dyspnea. Finally, chronic graft-versus-host disease can be accompanied by low immune function and frequent infections; it can also cause continuous reduction of platelets and bleeding.

Chronic graft-versus-host disease is an important cause of death for long-term survivors after hematopoietic stem cell transplantation in leukemia, accounting for about 1/4, and is also the main factor affecting the quality of life of patients.

Graft versus host disease diagnosis

Rely on biopsy.

Graft versus host disease treatment

Graft-versus-host disease is the most important complication after transplantation and the main cause of death after transplantation. Therefore, prevention and treatment of graft-versus-host disease is extremely important for ensuring successful transplantation and long-term survival after transplantation.

1. Treatment of acute graft-versus-host disease

The first-line treatment is methylprednisolone (an adrenocortical hormone) intravenously, and the dose can be increased according to the condition. Second-line treatment is one of tacrolimus and mycophenolate. Patients who have not responded well to second-line treatment are often used in combination with methylprednisolone. In addition, anti-T cell monoclonal antibodies (anti-CD3 monoclonal antibodies) can be used in patients with methylprednisolone ineffective. Anti-interleukin-2 receptor antibodies also have some effect.

The earlier the graft-versus-host disease appears, the worse the prognosis, especially those who appear within 10 days after transplantation, and should be actively treated as soon as possible.

2. Treatment of chronic graft-versus-host disease

The standard first-line treatment is prednisone plus azathioprine at an early stage, and gradually decreases after the condition improves, and the overall course of treatment is about 1 year. For those with thrombocytopenia and reduced bone marrow megakaryocytes, prednisone + cyclosporin A should be used. Those who are ineffective in the above treatment can choose second-line treatment drugs, such as one of tacrolimus and mycophenolate.

3. Treatment of refractory skin chronic graft-versus-host disease

Can use psoralen and ultraviolet A irradiation, most patients have improved skin lesions. In addition, as chronic graft-versus-host disease patients have low immune function and are prone to concurrent infections, the prevention and treatment of infections is also very important.

Graft versus host disease prevention

1. Prevention of acute graft-versus-host disease

(1) Donor selection Try to choose a transplant with a high degree of HLA compatibility between the donor and recipient.

(2) Aseptically strengthen environmental protection, place recipients in aseptic treatment of intestinal tract before laminar flow ward and transplantation.

(3) Choose effective immunosuppressive drugs for prevention after immunosuppressant transplantation. Cyclosporin A and methotrexate are the most basic drugs. In recent years, a new drug, such as tacrolimus and mycophenolate, has been added on this basis to improve the effect. Methotrexate can also be removed, and cyclosporin A plus one of the two new drugs mentioned above can be selected.

(4) Removal of T lymphocytes from T lymphocyte grafts (adding monoclonal antibodies against T cells). Although it can reduce graft-versus-host disease, it is easy to cause leukemia to relapse. Because the T lymphocytes in the graft are the main responsible for the damage to the corresponding target organs, but they are also the main force of the graft to fight the remaining leukemia cells in the body.

(5) Intravenous injection of gamma globulin in large doses.

2. Prevention of chronic graft-versus-host disease

Extending the use of immunosuppressants after transplantation, such as continued use of cyclosporin A six months after transplantation, can reduce the incidence of chronic graft-versus-host disease. Treatment of transplanted T cells (with anti-CD3 monoclonal antibody) can reduce the occurrence of chronic graft-versus-host disease, reducing the risk by 50%, but due to the reduction of chronic graft-versus-host disease, the coexisting anti-leukemia effect (Referred to as GVL) is also reduced, which is likely to cause relapse of leukemia, so the overall survival rate has not improved. Therefore, transplantation of T cells is still controversial and has not been widely adopted.