Post-Transplant Lymphoproliferative Disorder
Section snippets
Pathophysiology
EBV first was implicated as a cause for malignancy in 1964, when viral particles were discovered in a patient who had Burkitt's lymphoma [9]. Since then, EBV has been implicated as a causative factor in nasopharyngeal carcinoma, Hodgkin's lymphoma, and PTLD. A member of the herpesvirus family, EBV infects and immortalizes B cells. EBV infection usually is asymptomatic in childhood. If the primary infection occurs during adolescence or adulthood, however, infectious mononucleosis occurs.
Classification
PTLD represents a spectrum of lymphoid hyperproliferative states that includes benign conditions, such as infectious mononucleosis-like illnesses and lymphoid hyperplasia, and malignancies, such as B-cell (and, rarely, T-cell) lymphomas, which may take a fulminant course [5]. These disorders generally are associated with EBV infection (either primary infection or reactivation), but there are post-transplant lymphoid neoplasms that are not associated with EBV. Some studies suggest that
Diagnosis and staging
As is the case with all suspected lymphomas, it is critically important to obtain sufficient tissue for diagnosis, usually by excisional biopsy of the involved tissue or lymph node. Current recommendations for identifying a PTLD lesion are described in Table 2.
Noninvasive diagnosis of PTLD is not yet possible, although two blood tests may have some use. Polymerase chain reaction (PCR) testing of the peripheral blood for the presence of EBV-derived DNA is one promising method, but published
Post-transplant lymphoproliferative disorder in solid organ transplant recipients
The risk of developing PTLD after solid organ transplantation is variable and is most dependent on the level of immunosuppression, particularly with specific antilymphocyte therapy. All solid organ transplant recipients are at increased risk for many malignancies, especially those of lymphoid origin [30]. Table 3 lists the observed risk factors for the development of PTLD in solid organ transplant patients. Although many younger patients have not yet been exposed to EBV, it is not clear if the
Post-transplant lymphoproliferative disorder in hematopoietic stem cell transplant recipients
HSCT is performed primarily to cure malignancies and less commonly to treat severe autoimmune, immune deficiency, or metabolic diseases. (For a detailed discussion of HSCT, see the article by Cutler and Antin elsewhere in this issue.) Briefly, HSCT involves the administration of myeloablative doses of chemotherapy or radiation, followed by infusion of stem cells which return to the marrow and reconstitute hematopoiesis in 10 to 21 days, depending on the conditioning regimen and source of cells.
Surveillance
There recently has been interest in surveillance, prophylaxis, and early treatment of PTLD. Experience with monitoring for PTLD is limited, and there are no prospective randomized clinical trials of early interventions. Several compelling reports, however, suggest that surveillance for the presence of primary or reactivated EBV infection may prove useful, and there are small series suggesting that preemptive therapy may prevent PTLD effectively.
Several groups have examined solid organ
Antiviral therapy
Initial attempts to prevent PTLD in the solid organ transplant population focused primarily on using thymidine kinase inhibitors, such as ganciclovir or acyclovir, to eradicate or control EBV in a prophylactic setting for high-risk patients [25], [64], [65], [66], [67]. These drugs inhibit the replication of the EBV-related herpes viruses, herpes simplex, and cytomegalovirus. In vivo, however, these drugs are ineffective against EBV, because EBV-associated lymphomas do not express thymidine
Summary
PTLD is an increasingly recognized complication of solid organ transplantation and HSCT. Prompt diagnosis is key and requires high levels of clinical vigilance. Surveillance for PTLD by monthly PCR for circulating EBV DNA may be appropriate, particularly in such high-risk settings as EBV-seromismatched (donor-positive, recipient-negative) solid organ transplants and T-cell–depleted, HLA-mismatched stem cell transplants. When possible, surgical excision of the node, mass, or affected organ
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This work was supported by grant no. CA76931 from the National Institutes of Health (to A.W. Loren) and by a Career Development Award from the American Society of Clinical Oncology (to D.E. Tsai).