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Posttransplant lymphoproliferative disorders – causes, symptoms, diagnosis, treatment, pathology


Posttransplant lymphoproliferative disorders,
or PTLDs, are uncontrolled growths of cells called lymphocytes that may occur in transplant
recipients after receiving a solid organ, such as a kidney or a lung, or stem cells.
Transplant recipients require medications to suppress their immune systems which may
contribute to the development of a PTLD. Normally, immune cells can differentiate between
healthy “self” and “other” cells by inspecting for the presence or absence of
the normal “self” major histocompatibility complexes, also called human leukocyte antigens,
present on the surface of every cell that contains a nucleus. Healthy “self” cells
are left alone. “Others” include cells from other people or donors and “self”
cells that are infected, damaged, or stressed. Lymphocytes, are a class of rapidly dividing
cells and, therefore, tends to develop mutations more often. B-lymphocytes, or B-cells, work
to develop antibodies toward invading microbes. There’s also two types of T-lymphocytes,
or T-cells. Cytotoxic T-cells can directly destroy “other” cells and helper T-cells
assist other immune cells. Normally, if B-cells start to replicate out of control, it’s the
T-cells that keep them in check, and keep the immune response organized. When people receive a transplanted organ or
stem cells, they also must take immunosuppressive medications to prevent the immune system from
rejecting, or attacking, the transplant. In PTLDs, immunosuppression also prevents the
destruction of abnormal lymphocytes that exhibit uncontrolled replication. Resulting uncontrolled
growth of lymphocytes can either be a benign hyperplasia, meaning there’s a large collection
of noncancerous cells, or the cells can become malignant, resulting in a cancer called lymphoma. While PTLD may result from the overproduction
of T-cells, it is more typically associated with the overproduction of B-cells. One cause
of PTLD is Epstein-Barr virus, which is contracted early in life by most people through contact
with infected saliva. It lies dormant in B-cells, and can reactivate either inside the recipient’s
B cells or from donor B-cells that catch a ride inside solid organs or stem cell transplant
vials. Because of the immunosuppressive medications, T-cells are unable stop B-cells from replicating. Signs and symptoms of PTLDs can range from
a small mass within a lymph node anywhere in the body to much larger masses along with
the constitutional “B symptoms” of fevers, weight loss, and night sweats, that are seen
in malignant lymphomas. Widespread metastasis can lead to severe dysfunction of any affected
tissue. Risk factors include the type of immunosuppressive
medication used and the degree of immunosuppression that it causes, whether or not the person
has antibodies to Epstein-Barr virus, fewer similarities between the donor and recipient
major histocompatibility complexes, previous development of cancer, and being younger. Diagnosis of PTLDs may include blood tests,
tissue biopsies to determine what type of cancer is present, and imaging such as a PET
or CT scan to help determine whether the cancer has spread to other sites in the body. Treatment aims to eliminate the PTLD while
minimizing harm to the transplant, and may include surgery, radiation therapy, and chemotherapy.
If the cancer is caused by B-cells that produce the surface protein CD20, a manufactured antibody
called Rituximab may be used. There are several potential therapies for these conditions that
are currently in the investigational stages of development. All right, as a quick recap…Posttransplant
lymphoproliferative disorders, or PTLDs, are uncontrolled growths of lymphocytes that occur
after someone has received a solid organ or stem cell transplant that requires immunosuppressive
medications to prevent transplant rejection. They can originate in either type of lymphocyte:
B-cells or T-cells. Diagnosis involves blood tests, a biopsy, and imaging, while treatment
may include surgery, chemotherapy, and radiation.

6 thoughts on “Posttransplant lymphoproliferative disorders – causes, symptoms, diagnosis, treatment, pathology

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