Clinicopathological characteristics and rituximab addition to cytotoxic therapies in patients with rheumatoid arthritis and methotrexate‐associated large B lymphoproliferative disorders. Issue 1 (5th February 2015)

• Record Type: Journal Article
• Authors: Yamada, Kozue; Oshiro, Yumi; Okamura, Seiichi; Fujisaki, Tomoaki; Kondo, Seiji; Nakayama, Yoshifuku; Suematsu, Eiichi; Tamura, Kazuo; Takeshita, Morishige
• Is Part Of: Histopathology. Volume 67:Issue 1(2015)
• Page Start: 70
• Page End: 80
• Publication Date: 2015-02-05
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12627
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" id="his12627-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="his12627-sec-0001" sec-type="section"> <title>Aims</title> <p>To analyse the clinicopathological characteristics and prognosis of 40 rheumatoid arthritis (RA) patients with methotrexate (MTX)‐associated large B cell lymphoproliferative disorders (MTX–BLPD).</p> </sec> <sec id="his12627-sec-0002" sec-type="section"> <title>Methods and results</title> <p>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) (<italic>P </italic><<italic> </italic>0.01). Using <italic>in‐situ</italic> hybridization, Epstein–Barr virus (EBV) was detected in tumour cells of 25 of 40 RA patients with MTX–BLPD (63%). Immunohistologically, BCL2 expression was detected in 35% of patients with MTX–BLPD, which was lower than 93% of control DLBCL patients (<italic>P </italic><<italic> </italic>0.01). Eleven patients with EBV<sup>+</sup> 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 (<italic>P </italic><<italic> </italic>0.05). Among the 15 patients, seven with MTX–BLPD showed better overall survival than nine control DLBCL patients (<italic>P </italic><<italic> </italic>0.01).</p> </sec> <sec id="his12627-sec-0003" sec-type="section"> <title>Conclusions</title> <p>In RA patients with MTX–BLPD, immunosuppression by MTX, EBV infection and low BCL2 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.</p> </sec> </abstract>