Ebstein Barr Virus (EBV) associated development of Post transplantation lymphoproliferative disorder (PTLD) in a heart transplant recipient

Aims: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication following solid organ transplantation, and is the second most common malignancy in this patient population. Many posttransplant lymphomas develop from the uncontrolled proliferation of Epstein-Barr-virus (EBV)-infected B-cells, whereas EBV-negative PTLDs have increasingly been recognized within the past decade.

Case: We report on a 47-year-old EBV-seronegative male who developed biopsy-proven EBV positive post-transplantation lymphoproliferative disorder (PTLD) one year after successful cardiac transplantation secondary to ischemic cardiomyopathy while being treated with immunosuppressive agents. He was on maintenance immunosuppression of cyclosporine (85mg bid), everolimus (1.25mg bid), and prednisolone (5mg per day).

During routine follow-up elevated markers suggestive of an infection (CRP, Leucocytosis) were found and chest x-ray showed bi – pulmonary masses. Antibiotic treatment was instantly initiated based on the assumed diagnosis of bacterial pneumonia. Since clinical condition did not improve, CT-guided puncture of the susceptive nodules was indicated yielding material for histologic evaluation. A high-malignant diffuse large B-cell-lymphoma was diagnosed and tested positive for EBV with in-situ hybridization. Anti-infectious medication was terminated and therapy with Monoclonal antibody (rituximab) was initiated, followed by seven cycles of chemotherapy (cyclophosphamide, caelyx, vincristine, dexamethasone) and low-dose immunosuppressive maintainance therapy (cyclosporine, everolimus). Over the next 6 months, the pulmonary masses gradually decreased in size.

Ten months after the initial diagnosis, routine follow-up in our outpatient heart failure clinic demonstrated complete remission by serial CT-scans. At present, the clinical condition of this patient is stable with satisfactory organ function.

Discussion: Development of PTLD is frequent in solid organ transplant candidates and is associated with high morbidity and mortality. We report a case under maintainance therapy with cyclosporine and everolimus. Monoclonal antibody therapy (rituximab) and adjunctive chemotherapy was successful in inducing complete remission so far.