Full Papers
Involvement of Epstein-Barr virus in the development and spontaneous regression of methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis
N. Kitamura1, K. Sugiyama2, Y. Nagasawa3, M. Hamaguchi4, H. Kobayashi5, M. Takei6
- Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. kitamura.noboru@nihon-u.ac.jp
- Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
- Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
- Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
- Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
- Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
CER14569
2022 Vol.40, N°7
PI 1330, PF 1335
Full Papers
PMID: 34369356 [PubMed]
Received: 26/02/2021
Accepted : 12/07/2021
In Press: 05/08/2021
Published: 04/07/2022
Abstract
OBJECTIVES:
Conventionally, some patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) undergo spontaneous tumour regression after cessation of MTX. Although the involvement of Epstein-Barr virus (EBV) in the development and spontaneous regression has been suggested, the underlying mechanism remains unknown. In this study, we analysed patients who had developed MTX-LPD to evaluate the association between the development and spontaneous regression of MTX-LPD with EBV.
METHODS:
We analysed the age, stage, disease activity, MTX dose, lymphocyte count, EBV real-time polymerase chain reaction (PCR) test value, and EBV-encoded small RNA (EBER) positivity rate in patients with MTX-LPD at our hospital. Moreover, we investigated the factors related to spontaneous regression, which is a characteristic of MTX-LPD.
RESULTS:
Thirty-four patients were enrolled in this study. The MTX dose at LPD onset was 8.3±2.0 mg/week, and the total dose of MTX was 1,530.3±779.2 mg. The EBV load in the peripheral blood was 270.4±431.8 copy/μL, and the pathological tissues of 17 of 34 (50%) patients tested positive for EBER. Twenty-one patients had spontaneous regression after discontinuation of MTX. The factors related to spontaneous regression were examined using a univariate analysis, and the EBV real-time PCR test value in the peripheral blood, EBER in pathological tissues, and improvement rate of lymphocyte count were considered significant factors. The EBV real-time PCR test value in the peripheral blood was defined as an independent factor of spontaneous regression using a multivariate analysis of related factors.
CONCLUSIONS:
EBV may be involved in the development of MTX-LPD and its spontaneous regression.