Immunomodulator agent-related lymphoproliferative disorders

The recent development of inhibitors of key immune response proteins has revolutionized the therapy of autoimmune diseases; these immunomodulator agents include monoclonal antibodies and receptor antagonists. However, as with all therapies, these new agents are not without side effects and complicat...

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Bibliographic Details
Published in:Modern pathology 2009-12, Vol.22 (12), p.1532-1540
Main Authors: Hasserjian, Robert P, Chen, Steve, Perkins, Sherrie L, de Leval, Laurence, Kinney, Marsha C, Barry, Todd S, Said, Jonathan, Lim, Megan S, Finn, William G, Medeiros, L Jeffrey, Harris, Nancy L, O'Malley, Dennis P
Format: Article
Language:English
Subjects:
6-Mercaptopurine
Adult
Aged
Antagonists
Antigens
Antineoplastic Agents - therapeutic use
Autoimmune diseases
Autoimmune Diseases - drug therapy
Autoimmune Diseases - immunology
B-cell lymphoma
Belgium
Chemotherapy
Cytokines
Epstein-Barr virus
Female
Herpesvirus 4, Human - isolation & purification
Hodgkin Disease - chemically induced
Hodgkin's disease
Humans
Iatrogenesis
Iatrogenic Disease
Immune response
Immunologic Factors - adverse effects
Immunomodulation
Immunoproliferative diseases
Immunosuppression
Immunosuppressive agents
Immunosuppressive Agents - adverse effects
Infection
Lymphocytes B
Lymphoma
Lymphoma, B-Cell - chemically induced
Lymphoma, T-Cell - chemically induced
Lymphoproliferative Disorders - chemically induced
Lymphoproliferative Disorders - drug therapy
Lymphoproliferative Disorders - pathology
Lymphoproliferative Disorders - virology
Male
Methotrexate
Middle Aged
Monoclonal antibodies
Pathology
Rheumatoid arthritis
Side effects
T-cell lymphoma
Treatment Outcome
Tumor necrosis factor- alpha
Tumor necrosis factor-TNF
United States
Vasculitis
Young Adult
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Summary:The recent development of inhibitors of key immune response proteins has revolutionized the therapy of autoimmune diseases; these immunomodulator agents include monoclonal antibodies and receptor antagonists. However, as with all therapies, these new agents are not without side effects and complications. In particular, anti-tumor necrosis factor alpha (TNFalpha) agents have been reported to be associated with an increased incidence of lymphoproliferative disorders, infections, and vasculitis. We evaluated the clinicopathological features of 18 cases of immunomodulator agent-related lymphoproliferative disorders (IAR-LPD) from several institutions. These included 6 cases of B-cell lymphoma, 2 cases of T-cell lymphoma, 3 cases of classical Hodgkin lymphoma, and 7 atypical lymphoid proliferations that did not fulfill diagnostic criteria for lymphoma; two of the latter regressed after discontinuation of the immunomodulator agent therapy. All eight lymphoma patients with available information had also received prior chemotherapy (methotrexate or 6-mercaptopurine). EBV was strongly associated with the B-cell and classical Hodgkin lymphomas. This case series illustrates that a broad range of lymphoid proliferations can occur after immunomodulator agent therapy and that these immunomodulator agent-related lymphoproliferative disorders have considerable overlap with other well-defined lymphoproliferative diseases associated with iatrogenic immunosuppression. Further study is warranted to evaluate how these therapies interact with other immunosuppressive agents and the underlying abnormal immune system to enhance the development of lymphomas and atypical lymphoid proliferations.
ISSN:0893-3952
1530-0285
DOI:10.1038/modpathol.2009.131