Clinicopathological characteristics and rituximab addition to cytotoxic therapies in patients with rheumatoid arthritis and methotrexate-associated large B lymphoproliferative disorders.

Abstract

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, BCL2 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 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.

• Authors: Kozue Yamada, Yumi Oshiro, Seiichi Okamura, Tomoaki Fujisaki, Seiji Kondo, Yoshifuku Nakayama, Eiichi Suematsu, Kazuo Tamura, Morishige Takeshita
• Journal: Histopathology (Histopathology) Vol. 67 Issue 1 Pg. 70-80 (Jul 2015) ISSN: 1365-2559 [Electronic] England
• PMID: 25429725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Antirheumatic Agents
• Proto-Oncogene Proteins c-bcl-2
• RNA, Viral
• Receptors, Interleukin-2
• Rituximab
• Methotrexate

Topics

• Adult
• Aged
• Aged, 80 and over
• Antirheumatic Agents (adverse effects, therapeutic use)
• Arthritis, Rheumatoid (drug therapy, pathology, virology)
• Epstein-Barr Virus Infections (diagnosis)
• Female
• Herpesvirus 4, Human (genetics, isolation & purification)
• Humans
• In Situ Hybridization
• Lymphoma, Large B-Cell, Diffuse (blood, chemically induced, pathology, virology)
• Male
• Methotrexate (adverse effects)
• Middle Aged
• Proto-Oncogene Proteins c-bcl-2 (blood)
• RNA, Viral (genetics)
• Receptors, Interleukin-2 (blood)
• Rituximab (therapeutic use)