Post-transplant lymphoproliferative disorder
Encyclopedia
Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B-cell proliferation due to therapeutic immunosupression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B-cells may undergo mutations which will render them malignant, giving rise to a lymphoma
.
In some patients, the malignant cell clone can become the dominant proliferating cell type, leading to frank lymphoma, a group of B cell
lymphoma
s occurring in immunosuppressed
patients following organ transplant
.
. Production of an interleukin-10, an endogenous anti-T cell cytokine
, has also been implicated.
In immunocompetent patients, Epstein-Barr virus causes infectious mononucleosis
, characterised by a proliferation of B-lymphocytes which is controlled by Suppressor T cells.
However, calcineurin inhibitors (tacrolimus
and cyclosporine), used as immunosuppressants in organ transplantation inhibit T cell
function, and can prevent the control of the B cell proliferation.
Depletion of T cells by use of anti-T cell antibodies
in the prevention or treatment of transplant rejection
further increases the risk of developing post-transplant lymphoproliferative disorder. Such antibodies include ATG
, ALG
and OKT3
.
Polyclonal PTLD may form tumor masses and present with symptoms due to a mass effect, e.g. symptoms of bowel obstruction
. Monoclonal forms of PTLD tend to form a disseminated malignant lymphoma.
medication, and can also be treated with addition of anti-viral therapy. In some cases it will progress to non-Hodgkin's lymphoma and may be fatal.
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
.
In some patients, the malignant cell clone can become the dominant proliferating cell type, leading to frank lymphoma, a group of B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s occurring in immunosuppressed
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
patients following organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
.
Causes
The disease is an uncontrolled proliferation of B cell lymphocytes following infection with Epstein-Barr virusEpstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
. Production of an interleukin-10, an endogenous anti-T cell cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
, has also been implicated.
In immunocompetent patients, Epstein-Barr virus causes infectious mononucleosis
Infectious mononucleosis
Infectious mononucleosis is an infectious, widespread viral...
, characterised by a proliferation of B-lymphocytes which is controlled by Suppressor T cells.
However, calcineurin inhibitors (tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
and cyclosporine), used as immunosuppressants in organ transplantation inhibit T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
function, and can prevent the control of the B cell proliferation.
Depletion of T cells by use of anti-T cell antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
in the prevention or treatment of transplant rejection
Transplant rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after...
further increases the risk of developing post-transplant lymphoproliferative disorder. Such antibodies include ATG
Anti-thymocyte globulin
Anti-thymocyte globulin is an infusion of horse or rabbit-derived antibodies against human T cells which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia.-Uses:...
, ALG
Anti-lymphocyte globulin
Anti-lymphocyte globulin is an infusion of horse-derived or more commonly rabbit-derived antibodies against human T cells which is used in the treatment of acute rejection in organ transplantation, especially in kidney transplants. It was developed at the University of Minnesota by Dr...
and OKT3
OKT3
Muromonab-CD3 is an immunosuppressant drug given to reduce acute rejection in patients with organ transplants. It is a monoclonal antibody targeted at the CD3 receptor, a membrane protein on the surface of T cells...
.
Polyclonal PTLD may form tumor masses and present with symptoms due to a mass effect, e.g. symptoms of bowel obstruction
Bowel obstruction
Bowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
. Monoclonal forms of PTLD tend to form a disseminated malignant lymphoma.
Treatment
PTLD may spontaneously regress on reduction or cessation of immunosuppressantImmunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
medication, and can also be treated with addition of anti-viral therapy. In some cases it will progress to non-Hodgkin's lymphoma and may be fatal.