Epstein-Barr Virus (EBV) Induced Polyclonal and Monoclonal B-Cell Lymphoproliferative Diseases Occurring after Renal Transplantation

Abstract

Nineteen renal allograft recipients developed B-cell lymphoproliferative diseases. Clinically there were two groups: a) young patients (mean age, 23 years) who presented soon (mean, 9 months) after transplantation or antirejection therapy with fever, pharyngitis, and lymphadenopathy resembling infectious mononucleosis, and b) older patients (mean age, 48 years) who presented later (mean, 6 years) after transplantation with localized tumor masses. Histologically, the diseases were classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic B-cell lymphoma (PBL). Immunologic cell typing revealed either polyclonal or monoclonal B-cell proliferations. Malignant transformation of polyclonal proliferations in two patients was suggested by the finding of clonal cytogenetic abnormalities. Epstein-Barr virus (EBV) specific serology, staining of biopsy specimens for the Epstein-Barr nuclear antigen, and EBV DNA molecular hybridization studies implicated EBV as the cause of both PDBH and PBL. Acyclovir, an antiviral agent that blocks EBV replication in vitro, inhibited oropharyngeal shedding of EBV and caused complete remission in four patients with polyclonal B-cell proliferations. The monoclonal tumors were acyclovir resistant. We suggest that surgical treatment, radiotherapy, or chemotherapy may be more appropriate therapy in selected patients with acyclovir resistant tumors. Therapeutic decisions require not only documentation of the viral etiology of these tumors, but also immunologic and cytogenetic analysis to determine the stage of tumor evolution in individual patients.

Reversibility of Lymphomas and Lymphoproliferative Lesions Developing Under Cyclosporin-Steroid Therapy

“…The theory continues that one of the rapidly multiplying B clones can undergo a chromosomal translocation, making it an autonomous monoclonal malignancy not easily influenced by immunological reconstitution or other therapy. 6,21 Whether such translocations occurred in the tumours described here is under study. However, it should be noted that in our series several seemingly monoclonal lesions involuted as readily as the polyclonal neoplasms.…”

“…19 However, their approach, in which surgical extirpation, irradiation, chemotherapy, and most recently the antiviral drug acyclovir are the principal therapeutic tools, has had an overwhelming mortality. 6 In contrast, the simple expedient herein reported of stopping or reducing immunosuppression in patients being treated with cyclosporin and prednisone has led to prompt and seemingly permanent resolution of lymphoproliferative tumours-provided that complications such as intestinal perforation or infection could be controlled. The only patients among 12 kidney or liver recipients whose lymphoproliferative lesions were not controlled were 2 (1 in each recipient category) who were not appropriately treated because of failure to make the diagnosis.…”

“…6 By the National Cancer Institute classification,10 most of the lesions were B cell malignant lymphomas of diffuse large cell type; 2 were atypical B cell proliferations. 6 of the neoplasms were considered polyclonal and 3 monoclonal, and 2 further cases exhibited both types of clonality.…”

“…4 The ominous implications of the term lymphoma have been softened by calling such tumours "pseudolymphomas" 5 or "lymphoproliferative disorders". 6 In this communication, we describe how lymphoproliferative neoplasms that developed under therapy with cyclosporin and steroids in renal, hepatic, and cardiac graft recipients, underwent resolution if immunosuppression was reduced or stopped-in contrast to a lethal course no matter what else was done in the absence of this simple step. The observations have shown that the much publicised cyclosporin lymphomas are relatively innocuous if appropriately treated.…”

Epstein-Barr Virus Infections and DNA Hybridization Studies in Posttransplantation Lymphoma and Lymphoproliferative Lesions: The Role of Primary Infection

“…Hanto et al [6] reported the results of studies on 19 renal transplant patients who developed lymphoproliferative disorders and lymphomas after transplantation. All the patients except one were receiving azathioprine, prednisone, and antithymocyte globulin.…”