Post-transplant lymphoproliferative disorders: implications for acquired immunodeficiency syndrome-associated malignancies.
Post-transplant lymphoproliferative disorders (PTLDs) comprise a histologic spectrum, ranging from hyperplastic-appearing lesions to frank non-Hodgkin's lymphoma or multiple myeloma histology. Multiple clones may coexist, each representing a discrete lymphomagenic event, a situation that is unique to immunodeficiency states. The incidence varies from 1% in renal recipients to 5% in heart recipients, but can be markedly increased by the use of anti-T-cell therapies or by T-cell depletion in bone marrow transplantation. PTLD continues to arise, even many years after transplantation, and late T-cell lymphomas have recently been recognized. Pretransplant Epstein-Barr virus (EBV) seronegativity increases risk to as high as 30%-50%. PTLD has a highly variable clinical picture; certain patterns are, however, seen. Reversibility of PTLD with reduction in immunosuppressives has long been recognized. Predicting reversibility has been difficult. The presence or absence of bcl-6 mutations has recently been identified as being of predictive value. Surgical resection can be curative. Cytotoxics, although problematic, can also be curative. Long-term remission has been achieved with anti CD21 and CD24 antibodies; efficacy has been reported for interferon alfa and for rituximab. In vitro expanded EBV-specific T cells have been effective as treatment and as prophylaxis in the setting of bone marrow transplantation. EBV viral load measured in blood appears to associate with the emergence of PTLD and may facilitate prophylactic studies. PTLD is a model of immunodeficiency-related EBV lymphomagenesis. Pathogenetic, therapeutic, and prophylactic insights gained from the study of PTLD are likely to be applicable to the acquired immunodeficiency syndrome setting.
Swinnen
L J
LJ
Division of Hematology/Oncology, Loyola University Chicago, Cardinal Bernardin Cancer Center, Rm. 245, 2160 S. First Ave., Maywood, IL 60153, USA. lswinne@luc.edu
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000635:transmission; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D019288:Herpesvirus 8, Human / Q000472:pathogenicity; D006801:Humans; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy / Q000009:adverse effects; D016483:Lymphoma, AIDS-Related / Q000209:etiology / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009369:Neoplasms / Q000209:etiology* / Q000276:immunology; D011183:Postoperative Complications; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000821:virology; D013601:T-Lymphocytes / Q000637:transplantation; D014180:Transplantation / Q000009:adverse effects; D014412:Tumor Virus Infections / Q000150:complications / Q000635:transmission; D014766:Viremia / Q000821:virology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000970:Antineoplastic Agents