Post-Transplant Lymphoproliferative Disorders (PTLD)

The risk of developing PTLD is higher for people who had a gut transplant or a transplantation of multiple organs. In case of a stem cell transplantation, the risk for PTLD is higher when the donor is not a perfect match. The risk for PTLD is highest during the first few months after a transplant, when patients receive a higher dose of immunosuppressive medication. However, in recipients of a solid organ transplant, there is a ‘second peak’ of PTLD many years after the transplant.

PTLD encompasses four main subtypes. In people with early PTLD, lymphocytes and other immune cells divide excessively and build up in lymph nodes. While these cells are not cancerous, there is a chance that they undergo a cancerous transformation if left untreated. In case of polymorphic PTLD, a mixture of abnormal lymphocytes (some of which may be cancerous) build up in lymph nodes and/or other body parts. The third and most common subtype consists of monomorphic PTLD. In this case, cancerous lymphocytes (mostly originating from B-lymphocytes) build up in lymph nodes and extranodal sites. These cancerous B-cells can look very similar to other types of non-hodgkin lymphoma, such as Burkitt lymphoma, or diffuse-large B-cell lymphoma (DLBCL). Classical Hodgkin lymphoma – PTLD type is the fourth and rarest of all PTLD subtypes. In these patients, the cancerous cells look very similar to the Reed-Sternberg cells that are typical for classical Hodgkin lymphoma.

PTLD is diagnosed by taking a biopsy from an affected part of the body. This tissue sample is sent to a laboratory, where a pathologist assesses whether the specimen contains lymphoma. In addition to this, further molecular and genetic tests are performed to determine the exact type of cancer cells.

If these analyses are indicative for PTLD, additional tests can be performed to assess how far the lymphoma has spread. This includes blood tests, a bone marrow biopsy to evaluate whether the PTLD has spread to the bone marrow and imaging tests (e.g., PET-CT, MRI) to look for signs of lymphoma in other areas of body.

In case of PTLD, the best chance for a successful treatment lies in an early detection of the disease. As a result, patients who underwent a transplant undergo regular blood tests to assess the level of the EBV DNA load in their blood. If the EBV level rises, physicians may opt to give a treatment to prevent the development of PTLD. In most cases, this preventive therapy consists of the monoclonal antibody rituximab. An alternative treatment strategy can be to reduce the dose of the immunosuppressive treatment.

If a PTLD develops, the first step is to reduce the level of the immunosuppressive therapy to the lowest dose possible. Importantly, this has to be done very carefully to prevent that the immune system of the patient rejects the transplant.

For patients with a more aggressive form of PTLD, or when a reduction in the immunosuppressive therapy does not lead to an improvement, a treatment with rituximab can be initiated. Of note, rituximab will only be effective if the PTLD originates from B-cells.

When also rituximab is unable to control the PTLD, patients will usually be treated with chemotherapy, either alone or in combination with rituximab.