Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases.

Salloum, Emile; Cooper, Dennis; Howe, Greg; Lacy, Jill; Tallini, Giovanni; Crouch, Jill; Schultz, M.; Murren, John R.

doi:10.1200/jco.1996.14.6.1943

Cited by 350 publications

(252 citation statements)

References 30 publications

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“…In RA patients treated with methotrexate, studies have shown varying results. EBV has been detected in 16-44% of lymphomas (14,15,26), and, as in the present study, a role for EBV in lymphoma development cannot be ruled out.…”

Section: Discussionsupporting

confidence: 53%

“…The reason for this association is still incompletely understood, but immunosuppressive therapy in RA (6)(7)(8)(9)(10) as well as Epstein-Barr virus (EBV) infection may play a role in the development of these lymphomas (11)(12)(13)(14)(15). Additionally, both we (16) and others (17) have reported that high RA disease activity in itself may be associated with an increased lymphoma risk.…”

mentioning

confidence: 99%

“…As a consequence of the present widespread use of disease-modifying antirheumatic drugs (DMARDs) in RA patients, most data concerning lymphoma features in RA patients are derived from studies and case reports in which patients were treated with different immunosuppressive drugs (12,14,(18)(19)(20)(21)(22)(23)(24)(25)(26). Information about lymphoma characteristics in RA patients not influenced by immunosuppressive drug treatment is limited.…”

mentioning

confidence: 99%

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Lymphoma subtypes in patients with rheumatoid arthritis: Increased proportion of diffuse large B cell lymphoma

Baecklund

Sundström

Ekbom

et al. 2003

Arthritis & Rheumatism

153

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Objective. Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphoma. It is not clear whether the increase is confined to certain subtypes of lymphomas. Immunosuppressive therapy and Epstein-Barr virus (EBV) have been linked to the development of these lymphomas. To gain information about the baseline pattern of lymphoma subtypes in RA before the current widespread use of immunosuppressive drugs, we examined the distribution of lymphoma subtypes and the presence of EBV in a cohort of RA patients with a low frequency and duration of treatment with immunosuppressive drugs.Methods. By linking data from the Swedish Hospital Discharge Register and the Swedish Cancer Register, 42 cases of lymphoma were identified among 11,683 patients with RA in the Uppsala Health Care Region between 1964 and 1984. The medical records and paraffin-embedded lymphoma tissues were collected, and the lymphomas were reclassified using the World Health Organization classification. In situ hybridization was used to detect EBV.Results. Tissues from 35 patients were reviewed. Non-Hodgkin's lymphoma (NHL) was found in 33 patients and Hodgkin's lymphoma in 2 patients. There was an increased frequency of diffuse large B cell lymphoma (DLBCL) (22 of 33 NHL patients, 67%) compared with that in the general population (30-40%). EBV was detected in 5 of 30 examined lymphomas from patients (17%). Twenty of the 22 DLBCL patients had RA with medium or high inflammatory activity, and 6 had been treated with a disease-modifying antirheumatic drug for >1 year.Conclusion. The findings of this study suggest an increased incidence of one specific lymphoma subtype,

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Section: Discussionsupporting

confidence: 53%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lymphoma subtypes in patients with rheumatoid arthritis: Increased proportion of diffuse large B cell lymphoma

Baecklund

Sundström

Ekbom

et al. 2003

Arthritis & Rheumatism

153

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“…Additionally, spontaneous regression was possible after the withdrawal of MTX in 88.9% of MTX-LPD patients (4). Therefore, EBV infection appears to contribute to RA-MTX-LPD onset (19).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, LPD developed by immunodeficient patients treated with MTX is defined as MTXassociated LPD (MTX-LPD) in the 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (3). MTX-LPD has the following characteristics: the Epstein-Barr virus (EBV) genome is present in lymphoma cells, and MTX withdrawal can potentially result in spontaneous regression of the lymphoma (4,5). However, the risk factors concerning MTX-LPD onset have not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Association of Higher Methotrexate Dose With Lymphoproliferative Disease Onset in Rheumatoid Arthritis Patients

Kameda

Dobashi

Miyatake

et al. 2014

Arthritis Care & Research

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Objective. Methotrexate (MTX) is used as an anchor drug for rheumatoid arthritis (RA). Lymphoproliferative disease (LPD) occasionally develops in patients treated with MTX, and is known as MTX-associated LPD (MTX-LPD).Although MTX-LPD occurs mainly in RA patients, it has not been established if MTX administration is an independent risk factor for LPD in RA patients. We examined the clinical characteristics of MTX-LPD in Japanese RA patients and attempted to determine the risk factors for MTX-LPD development. Methods. We performed a nested case-control study on RA patients. We enrolled 5,753 RA patients from Kagawa, Japan. In age-and sex-matched patients, we separated patients who did not develop LPD under MTX treatment (MTX non-LPD group) from those that did (MTX-LPD group) and conducted a comparative examination. We used multivariate analysis to determine the independent risk factors for MTX-LPD onset. Results. There were 28 patients in the MTX-LPD group and 125 patients in the MTX non-LPD group. Multivariate analysis of the parameters extracted by univariate analysis revealed that the mean MTX dose was a risk factor for MTX-LPD after adjusting for age; therefore, higher MTX dose is associated with LPD onset in RA patients. Conclusion. MTX is an independent risk factor for LPD onset in Japanese RA patients.

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Lymphoma Rates Are Low but Increased in Patients With Psoriasis

Gelfand¹,

Berlin²,

Voorhees³

et al. 2003

Arch Dermatol

231

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Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases.

Cited by 350 publications

References 30 publications

Lymphoma subtypes in patients with rheumatoid arthritis: Increased proportion of diffuse large B cell lymphoma

Lymphoma subtypes in patients with rheumatoid arthritis: Increased proportion of diffuse large B cell lymphoma

Association of Higher Methotrexate Dose With Lymphoproliferative Disease Onset in Rheumatoid Arthritis Patients

Lymphoma Rates Are Low but Increased in Patients With Psoriasis

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