Clinicopathologic investigation of methotrexate-induced lymphoproliferative disorders, with a focus on regression

Michihide Tokuhira, Shuntaro Saito, Ayumi Okuyama, Katsuya Suzuki, Morihiro Higashi, Shuji Momose, Takayuki Shimizu, Takehiko Mori, Tomoe Anan-Nemoto, Koichi Amano, Shinichiro Okamoto, Tsutomu Takeuchi, Jun Ichi Tamaru, Masahiro Kizaki

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


Although recent accumulative data reveal the clinicopathogenesis of regression in methotrexate-induced lymphoproliferative disorders (MTX-LPDs), the precise understanding including this category remains controversial. In this study, we analyzed 62 patients with MTX-LPD. Forty-three patients showed regression (Reg group), with high rates of Hodgkin lymphoma (HL) and LPD (90 and 88%, respectively). Among the 43 patients of the Reg group, 14 patients (33%) relapsed. The median duration before relapse in the Reg group was 10.6 months. Although the difference of OS between the Reg and Non-Reg groups was not significantly different, relapse-free patients in the Reg group had a superior overall survival (OS). MTX duration had a significant impact on Epstein–Barr virus (EBV) infection (p =.00131). Furthermore, EBV infection was significantly related to clinical manifestations, including spleen invasion, in the regression phenomenon. Some human leukocyte antigens (HLA) alleles might affect MTX-LPD development via EBV infection, although A*2402 and DRB1*0405 might be affected as fundamental factors.

Original languageEnglish
Pages (from-to)1143-1152
Number of pages10
JournalLeukemia and Lymphoma
Issue number5
Publication statusPublished - 2018 May 4


  • Methotrexate
  • autoimmune diseases
  • lymphoproliferative disorders
  • regression
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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