title: A clinical, pathological, and genetic characterization of methotrexate-associated lymphoproliferative disorders.
abstract: 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.
  
  
  CONCLUSIONS
  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that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD, had a better clinical outcome when MTX was withdrawn than did other patients with MTX-LPD.
authors: From the Department of Rheumatology and Clinical Immunology, the Department of Diagnostic Pathology, the Center for Genomic Medicine, and the Department of Hematology and Oncology, Kyoto University Graduate School of Medicine; the Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital; the HLA Foundation Laboratory, Kyoto, Japan.
authors: Noriyuki
authors: N
authors: Yamakawa
authors: Masakazu
authors: M
authors: Fujimoto
authors: Daisuke
authors: D
authors: Kawabata
authors: Chikashi
authors: C
authors: Terao
authors: Momoko
authors: M
authors: Nishikori
authors: Ran
authors: R
authors: Nakashima
authors: Yoshitaka
authors: Y
authors: Imura
authors: Naoichiro
authors: N
authors: Yukawa
authors: Hajime
authors: H
authors: Yoshifuji
authors: Koichiro
authors: K
authors: Ohmura
authors: Takao
authors: T
authors: Fujii
authors: Toshiyuki
authors: T
authors: Kitano
authors: Tadakazu
authors: T
authors: Kondo
authors: Kimiko
authors: K
authors: Yurugi
authors: Yasuo
authors: Y
authors: Miura
authors: Taira
authors: T
authors: Maekawa
authors: Hiroh
authors: H
authors: Saji
authors: Akifumi
authors: A
authors: Takaori-Kondo
authors: Fumihiko
authors: F
authors: Matsuda
authors: Hironori
authors: H
authors: Haga
authors: Tsuneyo
authors: T
authors: Mimori
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D017285:Polymyositis / Q000188:drug therapy; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D018501:Antirheumatic Agents; D006680:HLA Antigens; D008727:Methotrexate
keywords: HEMATOPOIETIC SYSTEM; HLA ANTIGENS; RHEUMATIC DISEASES; RHEUMATOID ARTHRITIS; SKIN MANIFESTATIONS