Background/Purpose: Recently, methotrexate (MTX) has been considered as the anchor drug in the treatment of rheumatoid arthritis (RA). However, it has been reported that MTX occasionally induced lymphoproliferative disorder (LPD) most of which is malignant lymphoma (ML), especially in Japan. MTX-LPD is one of the “other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD)” in the WHO classification. A line of evidence suggests that Epstein-Barr virus (EBV) infection may be involved in the pathogenesis of MTX-LPD, however, precise mechanism and the risk factor of MTX-LPD have not been known yet. Although some of MTX-LPD naturally improves by discontinuing MTX, other may need the chemotherapy for fatal ML. Taken together with the several reports showing that RA itself increases the risk of ML, this problem needs to be solved. Thus, we investigated clinical courses of 30 RA patients complicated with ML in our hospital.

Methods: We analyzed clinical characteristics and course of 30 RA patients complicated with ML retrospectively and compared their laboratory data with those from 1260 RA patients without ML in our department.

Results: Characteristics of the thirty patients (23 female); age 62.5±10.0 years, disease duration 9.2±0.6 years. Twenty-one were diagnosed as MTX-LPD. Three patients with MTX-LPD were naturally improved by discontinuing MTX, however, 2 of those patients were relapsed. Twelve patients among 15 patients with MTX-LPD on chemotherapy have continued to be complete remission. One patient died after chemotherapy. The dose of MTX was under 8mg/week in 13 among 15 patients and duration of MTX was under 5 years in 11 among 15 patients. The histological type of MTX-LPD was diffuse large B-cell lymphoma (DLBCL) in 16 patients. The most first-symptom is palpable tumors in 15 (50%) patients. Serum CRP was elevated 2 months before ML onset and LDH was elevated at the time of ML onset. The numbers of lymphocytes, hemoglobin and IgG were significantly lower and those of LDH, CRP and ESR were significantly higher compared with non-ML RA patients.

Conclusion: We clarified clinical characteristics of RA patients complicated with ML. From our study, the summarized clinical characteristics of MTX-LPD were as follows; age of onset; from 50 to 70 years old, MTX-duration; within 5 years when start to receive MTX, histology; DLBCL, and first symptom; palpable tumor. MTX-LPD developed in RApatients in spite of low dose MTX and relapsed patients exist after cessation of MTX. The levels of CRP rather than LDH might be elevated earlier before diagnosis of ML. Furthermore, low lymphocytes and IgG might be the risk factors of ML, including MTX-LPD.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-analysis-of-30-rheumatoid-arthritis-patients-complicated-with-malignant-lymphoma-especially-methotrexate-related-lymphoproliferative-disorder/