Abstract
Ten patients developing lymphomas after disease modifying anti-rheumatic drugs (DMARD) (methotrexate, n = 3, mean cumulative dose = 3.4 g; cyclophosphamide, n = 2, mean dose = 70 g; azathioprine, n = 6, mean dose = 243 g) were investigated. Methotrexate-related lymphomas were Epstein-Barr virus (EBV)-positive, had infrequent aberrant methylation of p15 and p16, and responded well to methotrexate withdrawal or anti-CD20 antibody (rituximab) alone without concomitant chemotherapy, implying that defective immunosurveillance was important in lymphomagenesis. However, 75% of cyclophosphamide/azathioprine-related lymphomas were EBV-negative, had frequent p15 and p16 methylation, and responded poorly to drug withdrawal and chemotherapy, implying that direct drug-induced mutagenesis might be involved in lymphomagenesis.
(c) 2005 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Agents / administration & dosage*
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Antirheumatic Agents / administration & dosage*
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Antirheumatic Agents / adverse effects
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Autoimmune Diseases / complications
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Autoimmune Diseases / drug therapy*
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Autoimmune Diseases / metabolism
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Burkitt Lymphoma / drug therapy*
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Burkitt Lymphoma / etiology
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Burkitt Lymphoma / metabolism
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Burkitt Lymphoma / virology
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Cell Transformation, Viral / drug effects
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Cyclin-Dependent Kinase Inhibitor p15 / metabolism
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism
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DNA Methylation / drug effects
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Female
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Herpesvirus 4, Human / metabolism
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Humans
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Male
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Middle Aged
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Mutagenesis / drug effects
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Retrospective Studies
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Rituximab
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Treatment Outcome
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Agents
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Antirheumatic Agents
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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Rituximab