Distinct decrease in peripheral lymphocytes in EBER-positive cases of MTX-LPD

Abstract

Objectives

To determine the clinical characteristics of methotrexate-associated lymphoproliferative disorder (MTX-LPD).

Methods

In this study, 12 RA patients who developed MTX-LPD were assessed. The peripheral blood lymphocyte (PBL) count at the onset of MTX-LPD was compared to that 6 months before the onset, in Epstein-Barr virus-encoded RNA (EBER)-positive and -negative subgroups. We examined the change in the PBL count after MTX withdrawal. In patients with relapsed LPD, changes in the PBL count before relapse were also examined.

Results

Regression of LPD after MTX withdrawal was noted in eight patients. In these patients, the PBL count was decreased at the onset of MTX-LPD compared to 6 months before the onset; the decrease was significantly more prominent in EBER-positive patients. In cases of spontaneous regression of LPD, the PBL count recovered quickly after MTX withdrawal. Four of eight patients showed a recurrence of LPD after they improved following MTX withdrawal. These patients also exhibited a decreased PBL count at recurrence compared to 6 months before recurrence.

Conclusion

A decrease in the PBL count might be involved in the pathogenesis of MTX-LPD, especially in EBER-positive cases and in patients with LPD relapse after MTX withdrawal following initial improvement.

Keywords:

• EBV
• lymphocyte
• MTX-LPD
• RA

Conflict of interest

Kondo M has received speaking fee from Eisai Co., Ltd., Chugai Pharma Co., Ltd., Mitsubishi-Tanabe Pharma, Bristol-Myers Squibb, Janssen Pharma K.K., Astellas Pharma Inc, Takeda Pharma Co., Nippon Kayaku Co., Ltd., Daiichi-Sankyo Co., Ltd., Asahi Kasei Pharma Co. and AbbVie Japan. Murakawa Y has received grants from Asahi Kasei Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., Teijin Pharma Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd. and Mitsubishi-Tanabe Pharma Corporation, instructor fees from Asahi Kasei Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd. and Janssen Pharmaceutical K.K. Eisai Co., Ltd. and speaking fees from Ono Pharmaceutical Co., Ltd., Mitsubishi-Tanabe Pharma Corporation, Astellas Pharma Inc., UCB Japan Co., Ltd., Chugai Pharmaceutical Co., Ltd., AbbVie Japan, Daiichi-Sankyo Co., Ltd., AYUMI Pharmaceutical Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Sanofi K.K., Teijin Pharma Ltd., Eli Lilly Japan K.K. and Eisai Co., Ltd. Moriyama M has received speaking fees from Mitsubishi-Tanabe Pharma Corporation, Janssen Pharmaceutical K.K. and manuscript fees from Sanofi K.K. Honda M has received speaking fees from Asahi Kasei Pharma Corporation and Ono Pharmaceutical Co., Ltd. Sugiura T has received speaking fee from Eisai Co., Ltd., Chugai Pharma Co., Ltd., Mitsubishi-Tanabe Pharma, Bristol-Myers Squibb, Astellas Pharma Inc., Asahi Kasei Pharma Co., AbbVie Japan and Pfizer Japan Inc. Watanabe Y has received speaking fee from Chugai Pharma Co., Ltd. and Mitsubishi-Tanabe Pharma. Kakimaru H has received speaking fee from Chugai Pharma Co., Ltd., Astellas Pharma Inc., Takeda Pharma Co., Daiichi-Sankyo Co., Ltd., and AbbVie Japan. Onoda K has no COI.