Therapy-related lymphomas in patients with autoimmune diseases after treatment with disease-modifying anti-rheumatic drugs.
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.
Au
Wing-Yan
WY
University Department of Medicine, Queen Mary Hospital, Hong Kong.
Ma
Edmond S K
ES
Choy
Carolyn
C
Chung
Lap-Ping
LP
Fung
Tsz-Kin
TK
Liang
Raymond
R
Kwong
Yok-Lam
YL
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000821:virology; D002472:Cell Transformation, Viral / Q000187:drug effects; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis / Q000187:drug effects; D012189:Retrospective Studies; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000069283:Rituximab