POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS NOT ASSOCIATED WITH EPSTEIN-BARR-VIRUS - A DISTINCT ENTITY

Purpose: Organ recipients are at a high risk of posttransplant lymphop roliferative disorders (PTLD) as a result of immunosuppressive therapy . Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) i nfection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. Patients and Methods: There were sev en kidney,three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outco me were compared with those in 21 patients with EBV-associated PTLD tr eated in our institution (group II). EBV was detected with at least tw o techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization wi th EBER 1 + 2 probes, Southern blotting, and detection of latent membr ane protein 1 (LMP1) expression by immunohistochemistry. Results: The rime between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,324; median, 1,800) and from 6 0 to 2,100 days in group II (mean, 546; median, 180), and was signific antly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV, All of the B-cell PTLDs in group I were classified as monomorphic, me eting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a co mponent of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were main ly bane marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in g roup I and nine in group II. The survival time was significantly longe r in group II (P < .01). Conclusion: EBV-negative PTLD may be ct late serious complication of organ transplantation, Half the tumors observe d after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.