A clinical, pathological, and genetic characterization of methotrexate-associated lymphoproliferative disorders

Noriyuki Yamakawa, Masakazu Fujimoto, Daisuke Kawabata, Chikashi Terao, Momoko Nishikori, Ran Nakashima, Yoshitaka Imura, Naoichiro Yukawa, Hajime Yoshifuji, Koichiro Ohmura, Takao Fujii, Toshiyuki Kitano, Tadakazu Kondo, Kimiko Yurugi, Yasuo Miura, Taira Maekawa, Hiroh Saji, Akifumi Takaori-Kondo, Fumihiko Matsuda, Hironori HagaTsuneyo Mimori

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


Objective. Methotrexate-associated lymphoproliferative disorders (MTX-LPD) often regress spontaneously during MTX withdrawal, but the prognostic factors remain unclear. The aim of our study was to clarify the clinical, histological, and genetic factors that predict outcomes in patients with MTX-LPD. Methods. Patients with MTX-LPD diagnosed between 2000 and 2012 were analyzed retrospectively regarding their clinical course, site of biopsy, histological typing, Epstein-Barr virus (EBV) in situ hybridization and immunostaining, and HLA type. Results. Twenty-one patients, including 20 with rheumatoid arthritis (RA) and 1 with polymyositis, were analyzed. The mean dose of MTX was 6.1 mg/week and the mean duration of treatment was 71.1 months. Clinically, 5 patients were diagnosed with EBV-positive mucocutaneous ulcer (EBVMCU) and had polymorphic histological findings. The proportion of those patients successfully treated solely by withdrawal of MTX was significantly greater than that of those without EBVMCU (75% vs 7.7%, p = 0.015). The HLA-B15:11 haplotype was more frequent in patients with EBV+ RA with MTX-LPD than in healthy Japanese controls (p = 0.0079, Bonferroni's method). EBV latency classification and HLA typing were not associated with the prognosis of MTX-LPD in our cohort. Conclusion. Our data demonstrate that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD, had a better clinical outcome when MTX was withdrawn than did other patients with MTX-LPD. (First Release Dec 15 2013; J Rheumatol 2014;41:293-9; doi:10.3899/jrheum.130270).

Original languageEnglish
Pages (from-to)293-299
Number of pages7
JournalJournal of Rheumatology
Issue number2
Publication statusPublished - 02-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology


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