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Clinicopathological characteristics and rituximab addition to cytotoxic therapies in patients with rheumatoid arthritis and methotrexate‐associated large B lymphoproliferative disorders
Author(s) -
Yamada Kozue,
Oshiro Yumi,
Okamura Seiichi,
Fujisaki Tomoaki,
Kondo Seiji,
Nakayama Yoshifuku,
Suematsu Eiichi,
Tamura Kazuo,
Takeshita Morishige
Publication year - 2015
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12627
Subject(s) - methotrexate , medicine , lymphoproliferative disorders , rheumatoid arthritis , rituximab , cytotoxic t cell , lymphoma , immunosuppression , gastroenterology , immunology , biology , biochemistry , in vitro
Aims To analyse the clinicopathological characteristics and prognosis of 40 rheumatoid arthritis ( RA ) patients with methotrexate ( MTX )‐associated large B cell lymphoproliferative disorders ( MTX – BLPD ). Methods and results Soluble interleukin 2 receptor titres (median 1500 U/ml) in 40 patients with MTX – BLPD were lower than those of 24 RA patients with non‐ MTX ‐ associated (non‐ MTX ) BLPD (5731 U/ml) and 15 with control diffuse large B cell lymphoma ( DLBCL , 5918 U/ml) ( P < 0.01). Using in‐situ hybridization, Epstein–Barr virus ( EBV ) was detected in tumour cells of 25 of 40 RA patients with MTX – BLPD (63%). Immunohistologically, BCL 2 expression was detected in 35% of patients with MTX – BLPD , which was lower than 93% of control DLBCL patients ( P < 0.01). Eleven patients with EBV + MTX – BLPD (44%) showed remission after MTX withdrawal. In RA patients with clinical stage III / IV BLPD , 15 with rituximab (R)+ cytotoxic therapies pursued better prognosis than 10 with R− cytotoxic therapies ( P < 0.05). Among the 15 patients, seven with MTX – BLPD showed better overall survival than nine control DLBCL patients ( P < 0.01). Conclusions In RA patients with MTX – BLPD , immunosuppression by MTX , EBV infection and low BCL 2 expression in tumour cells may play roles in tumorigenesis and tumour regression. R+ cytotoxic therapies as well as MTX withdrawal were highly effective in these patients.