Epstein-Barr virus associated post-transplant lymphoproliferative disorders: preventative measures and current treatments
De Leon, Sherryl A.
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Lymphoproliferative disorders develop in 1-20% of solid organ and hematopoietic stem cell transplant surgeries and continue to be serious and potentially fatal post-surgery complications for patients. Epstein-Barr virus, which is estimated to have infected over 90% of the adult population, is a major risk factor for the development of a post-transplant lymphoproliferative disorder (PTLD) and is linked to the majority of cases. PTLD can be defined as an aberrant growth of lymphocytes typically attributed to the standard practice of immunosuppressive therapy post hematopoietic stem cell transplant or solid organ transplant procedures. Disorders range from a relatively harmless benign plasmacytic hyperplasia to an aggressive malignant lymphoma. The complexity of the patient population diagnosed with PTLD, as well as the broad spectrum of clinical and pathological manifestations of the disorder, make the use of a standardized therapeutic strategy impractical. This reason can also be attributed to the fact that large scale, randomized, controlled trials of therapeutic regimens are lacking. However, reduction of immunosuppression (RI) remains a frontline therapeutic strategy for PTLD and several studies have found success in combining RI and rituximab, an antibody that targets B-lymphocytes. As with other lymphomas, radiation and/or surgery to excise localized tumors are still widely used in the management of this disorder. Chemotherapy is mainly used as a salvage therapy when all else fails, since mortality rates from drug toxicity effects remain high. Novel approaches have shown much promise in initial studies. They include adoptive immunosuppression with EBV-specific cytotoxic T-lymphocytes and antiviral agents and alternative immunosuppressants with antineoplastic effects that slow down B-cell proliferation. Further research should be done to confirm safety and efficacy of these new modalities. Research attention has turned to the discovery of prophylactic strategies and the improvement of methods to attain earlier diagnoses ofPTLD. An EBV vaccine is being developed to prevent EBV infection, since EBV-serostatus is the major risk factor for PTLD. Innovations in EBV-DNA load monitoring have been proven helpful in the early diagnosis of PTLD, when therapies are most effective. There have been many developments in the prophylactic and therapeutic approaches to PTLD, but more research should be done in the future to confirm their efficacies. Additionally, an algorithm for PTLD treatment recommendations should be developed using information from previous studies. The algorithm would help clinicians decide on the best treatment method for their patients based on the success of patients with similar characteristics.
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