RESEARCH - Remission of lymphoma after withdrawal of MTX in RA: relationship with type of latent Epstein-Barr virus infection

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Am J Hematol. 2007 Dec;82(12):1106-9.

Remission of lymphoma after withdrawal of methotrexate in rheumatoid

arthritis: relationship with type of latent Epstein-Barr virus

infection.

Miyazaki T, Fujimaki K, Shirasugi Y, Yoshiba F, Ohsaka M, Miyazaki K,

Yamazaki E, Sakai R, Tamaru J, Kishi K, Kanamori H, Higashihara M,

Hotta T, Ishigatsubo Y.

Department of Internal Medicine and Clinical Immunology, Yokohama City

University Graduate School of Medicine, Kanagawa, Japan.

Rheumatoid arthritis (RA) is associated with an increased risk of

developing lymphoma. Although the pathogenesis is still unclear, the

increased risk appears to be related to the high inflammatory activity

of RA, immunosuppressive agents, or Epstein-Barr virus (EBV)

infection. We investigated the relationship between EBV latent

infection and methotrexate (MTX)-associated lymphoma in RA patients.

Nine patients were diagnosed with non-Hodgkin's lymphoma (NHL) during

MTX treatment for RA in a multicenter study. The pathologic findings

were consistent with diffuse large B-cell lymphoma in 8 patients and

peripheral T-cell lymphoma, unspecified in 1. EBV infection was

detected in 3 patients by in situ hybridization. Among all 9 patients

who were initially treated by MTX withdrawal alone, 2 obtained

spontaneous complete response (CR), 1 had partial response, 2 had

stable disease (SD), and 4 had progressive disease. Both patients who

had a CR and 1 who had SD were positive for EBV. Further examination

of the latent EBV infection patterns revealed that 2 patients who

obtained a CR had latency Type III, and the other with SD had latency

Type II. These results demonstrate that immunodeficiency caused by MTX

treatment is associated with the development of EBV-related NHL in RA

patients. In patients who were treated by MTX for RA and developed

NHL, remission can be observed following MTX withdrawal especially in

NHL with latency Type III EBV infection. The analysis of EBV

infection, including the latency types, is useful to decide the

optimum therapeutic strategy.

PMID: 17654684

http://www.ncbi.nlm.nih.gov/pubmed/17654684

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