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.