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Lymphoma in Patients with Rheumatoid Arthritis

What is the Evidence of a Link with Methotrexate?

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Abstract

An increasing number of instances of lymphoma in patients with rheumatoid arthritis who are treated with methotrexate continue to appear. The majority of patients with lymphoproliferation have features of immunosuppression-associated lymphoma. Rheumatoid arthritis itself and the actions of methotrexate concur in leading to a immunosuppressed state.

Possible oncogenic mechanisms and the risk factors for patients with rheumatoid arthritis to develop lymphoma while receiving methotrexate include: (i) intense immunosuppression and severe disease in combination with genetic predisposition and; (ii) an increased frequency of latent infection with pro-oncogenic viruses like Epstein-Barr virus.

The aetiological role of methotrexate in the development of these lymphomas is supported by the spontaneous remission of these malignancies in some of patients with rheumatoid arthritis after methotrexate has been stopped. The physicians caring for patients with rheumatoid arthritis receiving methotrexate should be vigilant about signs and symptoms suggestive of lymphoma, mostly in those patients with significant comorbidity, long standing and severe disease who are more likely to be immunosuppressed. If a lymphoma appears in these patients, methotrexate should be stopped.

Spontaneous remission may occur and a period of observation is advisable when clinically possible. If functional deterioration appears or there are signs of lymphoproliferative organ invasion after several months then specific antineoplastic treatment should be instituted.

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References

  1. Symmons DP, Prior P, Scott DL, et al. Factors influencing mortality in rheumatoid arthritis. J Chronic Dis 1986; 39(2): 137–45

    Article  PubMed  CAS  Google Scholar 

  2. Weinblatt ME, Weissman BN, Holdsworth DE, et al. Long-term prospective study of methotrexate in the treatment of rheumatoid arthritis: 84-month update. Arthritis Rheum 1992; 35: 129–37

    Article  PubMed  CAS  Google Scholar 

  3. Weinstein A, Marlowe S, Korn J, et al. Low-dose methotrexate treatment of rheumatoid arthritis: long-term observations. Am JMed 1985; 79: 331–7

    CAS  Google Scholar 

  4. Kremer JM, Phelps CT. Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis: update after a mean of 90 months. Arthritis Rheum 1992; 35: 138–45

    Article  PubMed  CAS  Google Scholar 

  5. Furst DE, Erikson N, Clute L, et al. Adverse experience with methotrexate during 176 weeks of a longterm prospective trial in patients with rheumatoid arthritis. J Rheumatol 1990; 17: 1628–35

    PubMed  CAS  Google Scholar 

  6. Tishler M, Caspi D, Yaron M. Long-term experience with low dose methotrexate in rheumatoid arthritis. Rheumatol Int 1993; 13: 103–6

    Article  PubMed  CAS  Google Scholar 

  7. Bailin PL, Tindall JP, Roenigk HH, et al. Is methotrexate therapy for psoriasis carcinogenic? JAMA 1975; 232: 359–62

    Article  PubMed  CAS  Google Scholar 

  8. Rustin GHS, Rustin F, Dent J, et al. No increase in second tumors after cytotoxic chemotherapy for gestational tropho-blastic tumors. N Engl J Med 1983; 308: 473–6

    Article  PubMed  CAS  Google Scholar 

  9. Stern RS, Zierler S, Parrish JA. Methotrexate used for psoriasis and the risk of noncutaneous or cutaneous malignancy. Cancer 1982; 50: 869–72

    Article  PubMed  CAS  Google Scholar 

  10. Nyfors A, Jensen H. Frequency of malignant neoplasm in 248 long-term methotrexate treated psoriatics. Dermatologica 1983; 167: 260–1

    Article  PubMed  CAS  Google Scholar 

  11. Carmeli Y, Mevorach D, Kaminski N, et al. Regression of Kaposi’s sarcoma after intravenous immunoglobulin treatment for polymyositis. Cancer 1994; 72: 2859–61

    Article  Google Scholar 

  12. Harrison PV, Gorst DW, Fennell SJ, et al. Methotrexate, psoriasis, and malignancy. Lancet 1984; I: 996–7

    Google Scholar 

  13. Bologna C, Viu P, Jorgensen C, et al. Study of 8 cases of cancer observed in 458 rheumatoid arthritis (rheumatoid arthritis) patients treated with methotrexate (MTX) [abstract]. Arthritis Rheum 1995; 38: S206

    Google Scholar 

  14. Georgescu L, Geoffrey CQ, Schwartzman S, et al. Lymphoma in patients with rheumatoid arthritis: association with disease state or methotrexate treatment. Semin Arthritis Rheum 1997; (26): 794–804

    Article  PubMed  CAS  Google Scholar 

  15. Sany J, Anaya JM, Lussiez V, et al. Treatment of rheumatoid arthritis with methotrexate: a prospective open long term study of 191 cases. J Rheumatol 1991; 18: 1323–7

    PubMed  CAS  Google Scholar 

  16. Shiroky JB, Frost A, Skelton JD, et al. Complications of immunosuppression associated with weekly low dose methotrexate. J Rheumatol 1991; 18: 1172–5

    PubMed  CAS  Google Scholar 

  17. Ellman MH, Hurwitz H, Thomas C, et al. Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotrexate. J Rheumatol 1991; 18: 1741–3

    PubMed  CAS  Google Scholar 

  18. Kingsmore SF, Hall BD, Allen NB, et al. Association of methotrexate, rheumatoid arthritis and lymphoma: report of 2 cases and literature review. J Rheumatol 1992; 19: 1462–5

    PubMed  CAS  Google Scholar 

  19. Taillan B, Gamier G, Castanet J, et al. Lymphoma developing in a patient with rheumatoid arthritis taking methotrexate. Clin Rheumatol 1993; 12: 93–4

    Article  PubMed  CAS  Google Scholar 

  20. Kamel OW, van de Rijn M, Weiss LM, et al. Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med 1993; 328: 1317–21

    Article  PubMed  CAS  Google Scholar 

  21. Cobeta-Garcia JC, Ruiz-Jimeno MT, Fontova-Garrofe R. Non-Hodgkin’s lymphoma, rheumatoid arthritis and methotrexate [letter]. J Rhematol 1993; 20: 200–2

    CAS  Google Scholar 

  22. Morris CR, Morris AJ. Localized lymphoma in a patient with rheumatoid arthritis treated with parenteral methotrexate [letter]. J Rheumatol 1993; 12: 1272–3

    Google Scholar 

  23. Le Goff P, Koreichi A, Saraux A, et al. Lymphoma in a patient under low-dose methotrexate for rheumatoid arthritis: a new case [letter]. Rev Rhum Mal Osteoartic 1994; 61E: 330–1

    Google Scholar 

  24. Zimmer-Galler I, Lie JT. Choroidal infiltrates as the initial manifestation of lymphoma in rheumatoid arthritis after treatment with low-dose methotrexate. Mayo Clin Proc 1994; 69: 258–61

    PubMed  CAS  Google Scholar 

  25. Kamel OW, van de Rijn M, LeBrun DP, et al. Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: frequency of Epstein-Barr virus and other features associated with immunosuppression. Hum Pathol 1994; 25: 638–43

    Article  PubMed  CAS  Google Scholar 

  26. Lioté F, Pertuiset E, Cochand-Priollet B, et al. Methotrexate related B lymphoproliferative disease in a patient with rheumatoid arthritis: role of Epstein-Barr virus infection. J Rheumatol 1995; 22: 1174–8

    PubMed  Google Scholar 

  27. Davies JMS, Kremer JM, Furst DE, et al. Lymphomatous changes during methotrexate therapy [abstract]. Arthritis Rheum 1995; 38 Suppl.: S204

    Article  Google Scholar 

  28. Bachman TR, Sawitzke AD, Perkins SL, et al. Methotrexate associated lymphoma in patients with rheumatoid arthritis: report of two cases. Arthritis Rheum 1996; 39: 325–9

    Article  PubMed  CAS  Google Scholar 

  29. van de Rijn M, Michael LC, Variakojis D, et al. Epstein-Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis. Arthritis Rheum 1996; 39: 638–42

    Article  PubMed  Google Scholar 

  30. Ferraccioli GF, Casatta L, Bartoli E, et al. Epstein-Barr virus-associated Hodgkin’s lymphoma in a rheumatoid arthritis patient treated with methotrexate and cyclosporin A. Arthritis Rheum 1995; 38: 867–8

    Article  PubMed  CAS  Google Scholar 

  31. Moder KG, Tefferi A, Cohen MD, et al. Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospective study. Am J Med 1995; 99: 276–89

    Article  PubMed  CAS  Google Scholar 

  32. Williams CA, Block DA, Sibley J, et al. Lymphoma and leukemia in Rheumatoid arthritis: a matched case-control study in the Arheumatoid arthritisMIS (arthritis, rheumatism and aging medical information system) population [abstract]. Arthritis Rheum 1995; 38 Suppl.: S204

    Google Scholar 

  33. Shiroky JB, Newkirk MM. Reversible lymphomas [letter]. N Engl J Med 1993; 329: 1657–8

    PubMed  CAS  Google Scholar 

  34. Penn I. Cancers complicating organ transplantation. N Engl J Med 1990; 323: 1767–9

    Article  PubMed  CAS  Google Scholar 

  35. Knowles DM, Chamulak GA, Subar M, et al. Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1988; 108: 744–53

    PubMed  CAS  Google Scholar 

  36. Penn I. The changing pattern of posttransplant malignancies. Transplant Proc 1991; 23: 1101–3

    PubMed  CAS  Google Scholar 

  37. Penn I. Why do immunosuppressed patients develop cancer? Crit Rev Oncog 1989; 1: 27–52

    PubMed  CAS  Google Scholar 

  38. Biemer JJ. Malignant lymphomas associated with immunodeficiency states. Ann Clin Lab Sci 1990; 20: 175–91

    PubMed  CAS  Google Scholar 

  39. Hamilton DS, Pallesen G, Franzmann MB, et al. AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. Am J Pathol 1991; 138: 149–63

    Google Scholar 

  40. Nalesnic MA, Makowka L, Starzl TE. The diagnosis and treatment of posttransplant lymphoproliferative disorders. Curr Probl Surg 1988; 25: 367–472

    Article  Google Scholar 

  41. Cash JM, Klippel JH. Is malignancy a major concern in rheumatoid arthritis patients? J Clin Rheum 1995; 1: 14–22

    Article  CAS  Google Scholar 

  42. Symmons DP. Neoplasms of the immune system in rheumatoid arthritis. Am J Med 1985; 78 Suppl. 1A: 22–8

    Article  PubMed  CAS  Google Scholar 

  43. Staal SP, Ambinder R, Beschorner WE, et al. A survey of Epstein-Barr virus DNA in lymphoid tissue: frequent detection in Hodgkin’s disease. Am J Clin Pathol 1989; 91: 1–5

    PubMed  CAS  Google Scholar 

  44. Starzl TE, Nalesnik MA, Porter KA, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1984; I: 583–7

    Article  Google Scholar 

  45. Kassan SS, Thomas TL, Moutsopoulos HM, et al. Increased risk of lymphoma in sicca syndrome. Ann Intern Med 1978; 89: 888–92

    PubMed  CAS  Google Scholar 

  46. Shirai T, Hirose S, Okada T, et al. CD5+ B cells in autoimmune disease and lymphoid malignancy. Clin Immunol Immunopathol 1991; 59: 173–86

    Article  PubMed  CAS  Google Scholar 

  47. Burastero SE, Casali P, Wilder RL, et al. Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med 1988; 168: 1979–92

    Article  PubMed  CAS  Google Scholar 

  48. Kuryliszyn-Moskal A. Comparison of blood and synovial fluid lymphocytes subsets in rheumatoid arthritis and osteoarthritis. Clin Rheumatol 1995; 14(10): 43–50

    Article  PubMed  CAS  Google Scholar 

  49. Sakane T, Murakawa Y, Takeno M, et al. T cell interactions in active rheumatoid arthritis: insights from human autologus mixed reaction as a model of T cell activation cascade. Clin Exp Immunol 1991; 85(1): 55–60

    Article  PubMed  CAS  Google Scholar 

  50. Jones BM, Cheng IK, Wong RW. Aberrant T-regulation in rheumatoid arthritis and IgA nephropathy affects CD5+ and CD5-B lymphocytes equally. Clin Exp Immunol 1991; 86(2): 212–8

    Article  PubMed  CAS  Google Scholar 

  51. Brown-Galatola CH, Hall ND. Impaired suppressor cell activity due to surface sulphydryl oxidation in rheumatoid arthritis. BrJ Rheumatol 1992; 31(9): 599–603

    Article  CAS  Google Scholar 

  52. Young CL, Adamson TC III, Vaughan JH, et al. Immunohistological characterization of synovial membrane lymphocytes in rheumatoid arthritis. Arthritis Rheum 1984; 27: 32–9

    Article  PubMed  CAS  Google Scholar 

  53. Dobloug JH, Forre O, Kvien TK, et al. Natural killer cell activity of peripheral blood, synovial tissue lymphocytes from patients with rheumatoid arthritis and juvenile rheumatoid arthritis. Ann Rheum Dis 1982; 41: 490–4

    Article  PubMed  CAS  Google Scholar 

  54. Fox RI, Fong S, Tsoukas C, et al. Characterization of recirculating lymphocytes in rheumatoid arthritis patients: selective deficiency of natural killer cells in thoracic duct lymph. J Immunol 1984; 132: 2883–7

    PubMed  CAS  Google Scholar 

  55. Depper JM, Bluestein HG, Zvaifler NJ. Impaired regulation of Epstein-Bar virus induced lymphocyte proliferation in rheumatoid arthritis due to a T cell defect. J Immunol 1981; 127: 1899–902

    PubMed  CAS  Google Scholar 

  56. Tosato G, Steinberg AD, Yarchoan R, et al. Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis. J Clin Invest 1984; 73: 1789–95

    Article  PubMed  CAS  Google Scholar 

  57. Kahan A, Kahan A, Amor B, et al. Different defects of T cell regulation of Epstein-Barr virus-induced B cell activation in rheumatoid arthritis. Arthritis Rheum 1985; 28: 961–70

    Article  PubMed  CAS  Google Scholar 

  58. Bannwart B, Labat L, Moride Y, et al. Methotrexate in rheumatoid arthritis. An update. Drugs 1994; 47: 25–50

    Article  Google Scholar 

  59. Merrill JT, Shen C, Schreibman D, et al. Adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes. Arthritis Rheum 1997; 40: 1308–15

    PubMed  CAS  Google Scholar 

  60. Hersh EM, Carbone PP, Wong VG, et al. Inhibition of the primary immune response in man by antimetabolites. Cancer Res 1965; 25: 997–1002

    PubMed  CAS  Google Scholar 

  61. Benedict WF, Banerjee A, Gardner A, et al. Induction of morphological transformation in mouse C3H/10T1/2 clone 8 cells and chromosomal damage in hamster A (T1)C 1–3 cells by cancer chemotherapeutic agents. Cancer Res 1977; 37: 2202–8

    PubMed  CAS  Google Scholar 

  62. Benedict F, Baker MS, Haroun L, at al. Mutagenicity of cancer chemotherapeutic agents in the salmonella/microsome test. Cancer Res 1977; 37: 2209–13

    PubMed  CAS  Google Scholar 

  63. Ryan TJ, Boddington MM, Spriggs AI. Chromosomal abnormalities produced by folic acid antagonists. Br J Dermatol 1965; 77: 546–55

    Google Scholar 

  64. Jensen MK, Nyfors A. Cytogenetic effect of methotrexate on human cells in vivo: comparison between results obtained by chromosome studies on bone marrow cells and blood lymphocytes and by the micronucleus test. Mutat Res 1979; 64: 339–43

    Article  PubMed  CAS  Google Scholar 

  65. Marquardt H, Marquardt H. Induction of malignant transformation and mutagenesis in cell cultures by cancer chemotherapeutic agents. Cancer 1977; 40: 1930–4

    Article  PubMed  CAS  Google Scholar 

  66. Melnik J, Duffy DM, Sparkes RS. Human mitotic and meiotic chromosome damage following in vivo exposure to methotrexate. Clin Genetics 1971; 2: 28–31

    Article  Google Scholar 

  67. Sieber SM, Adamson RH. Toxicity of antineoplastic agents in man: chromosomal aberrations, antifertility effects, congenital malformations, and carcinogenic potential. Adv Cancer Res 1975; 22: 57–155

    Article  PubMed  CAS  Google Scholar 

  68. Chow M, Rubin H. Ubiquitous, heritable damage in cell populations that survive treatment with methotrexate. Proc Natl Acad Sci USA 1997; 94: 8773–8

    Article  PubMed  CAS  Google Scholar 

  69. Banjeree A, Benedict WF. Production of sister chromatid exchanges by various cancer chemotherapeutic agents. Cancer Res 1979; 39: 797–9

    Google Scholar 

  70. Goodman LS, Gilman A. The pharmacological basis of therapeutics. New York: The MacMillan Company, 1955: 1430

    Google Scholar 

  71. Johnson Carol A, Russell AS, Kovithavongs T, et al. Measures of immunologie and inflammatory response in vitro in rheumatoid patients treated with methotrexate. J Rheumatol 1986; 12: 294–6

    Google Scholar 

  72. Yunis JJ, Soreng AL. Constitutive fragile sites and cancer. Science 1984; 226: 1199–204

    Article  PubMed  CAS  Google Scholar 

  73. Melief CJM. Tumor eradication by adoptive transfer of cyto-toxic T lymphocytes. Adv Cancer Res 1992; 58: 143–75

    Article  PubMed  CAS  Google Scholar 

  74. Hanna N, Fidler IJ. Role of natural killer cells in the destruction of circulating tumor emboli. J Natl Cancer Inst 1980; 65: 801–9

    PubMed  CAS  Google Scholar 

  75. Purtilo DT, DeFlorio D, Hutt LM, et al. Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. N Engl J Med 1977; 297: 1077–81

    Article  PubMed  CAS  Google Scholar 

  76. Fox R, Martin Lotz, Rhodes G, et al. Epstein Barr virus in rheumatoid arthritis. Rheum Dis Clin North Am 1985; 11(3): 665–85

    CAS  Google Scholar 

  77. Rowe M, Peng-Pilon M, Huen DS, et al. Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B-cell-specific response that is delayed relative to NF-kB activation and to induction of cell surface markers. J Virol 1994; 68: 5602–12

    PubMed  CAS  Google Scholar 

  78. Wang D, Liebowitz D, Kieff E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 1985; 43: 831–40

    Article  PubMed  CAS  Google Scholar 

  79. Gregory CD, Dive C, Henderson S, et al. Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis [letter]. Nature 1991; 349: 612–4

    Article  PubMed  CAS  Google Scholar 

  80. Fillingame RH, Jorstad Cm, Morris DR. Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A. Proc Natl Acad Sei U S A 1975; 72: 4042–5

    Article  CAS  Google Scholar 

  81. Bowlin TL, McKown BJ, Babcock GF, et al. Intracellular polyamine biosynthesis is required for interleukin 2 responsiveness during lymphocyte mitogenesis. Cell Immunol 1987; 106: 420–7

    Article  PubMed  CAS  Google Scholar 

  82. Pasquali JL, Mamont PS, Weryha A, et al. Immunosuppressive effects of (2R,5R)- 6-heptyne-2,5-diamine, an inhibitor of polyamine synthesis. I. Effects on mitogen- induced immunoglobulin production in human cultured lymphocytes. Clin Exp Immunol 1988; 72: 141–4

    PubMed  CAS  Google Scholar 

  83. Olsen NJ, Murray LM. Antiproliferative effects of methotrexate on peripheral blood mononuclear cells. Arthritis Rheum 1989; 32: 378–85

    Article  PubMed  CAS  Google Scholar 

  84. Bowlin TL, McKown BJ, Schroeder KK. Methylacetylenic putrescine (MAP) an inhibitor of polyamine biosynthesis reduces the frequency and cytolytic activity of alloantigen-induced lyt 2.2 positive lymphocytes in vivo. Int J Immunopharmacol 1989; 11: 259–65

    Article  PubMed  CAS  Google Scholar 

  85. Claverie N, Pasquali JL, Mamont PS, et al. Immunosuppressive effects of (2R,5R)-6-heptyne-2,5-diamine, an inhibitor of polyamine synthesis: II. Beneficial effects on the development of a lupus-like disease in MRL-lpr/lpr mice. Clin Exp Immunol 1988; 72: 293–8

    PubMed  CAS  Google Scholar 

  86. O’Callaghan JW, Bretscher P, Russell AS. The effect of low dose chronic intermittent parental methotrexate on delayed type hypersensitivity and acute inflammation in a mouse model. J Rheumatol 1986; 13: 710–4

    PubMed  Google Scholar 

  87. Nakajima A, Hakoda M, Yamanaka H, et al. Methotrexate (MTX) induces apoptosis in activated T cells [abstract]. Arthritis Rheum 1995; 38 Suppl.: S192

    Article  Google Scholar 

  88. Weinblatt ME, Trentham DE, Fraser PA, et al. Long term prospective trial of low dose methotrexate in rheumatoid arthritis. Arthritis Rheum 1988; 31: 167–75

    Article  PubMed  CAS  Google Scholar 

  89. Kremer JM. Lymphocyte subset analysis after long-term methotrexate therapy for rheumatoid arthritis [abstract]. Arthritis Rheum 1986; 29 Suppl.: S75

    Article  Google Scholar 

  90. O’Meara A, Headon B, Reen DJ. Effect of methotrexate on the immune responses in children with acute lymphatic leukemia. Immunopharmacology 1985; 9: 33–8

    Article  PubMed  Google Scholar 

  91. Boerbooms AMT, Kerstens PJSM, van Loenhout JWA, et al. Infections during low-dose methotrexate treatment in rheumatoid arthritis. Semin Arthritis Rheum 1995; 24: 411–21

    Article  PubMed  CAS  Google Scholar 

  92. Newkirk MM, Shiroki JB, Johnson N, et al. Rheumatic disease patients, prone to Sjögren’s syndrome and/or lymphoma, mount an antibody response to BHRF1, the Epstein-Barr viral homologue of BCL-2. Br J Rheumatol 1996; 35: 1075–81

    Article  PubMed  CAS  Google Scholar 

  93. Barich LL, Schwartz J, Barich D. Oral methotrexate in mice: a co-carcinogenic as well as anti-tumor agent to methylcholan-threne-induced cutaneous tumors. J Invest Dermatol 1962; 39: 615–9

    Article  CAS  Google Scholar 

  94. Rustia M, Shubick P. Life-span carcinogenicity tests with 4-amino-N10- methylpteroylglutamic acid (methotrexate) in Swiss mice and Syrian golden hamsters. Toxicol Appl Pharmacol 1973; 26: 329–38

    Article  PubMed  CAS  Google Scholar 

  95. Burke JS, Butler JJ, Fuller LM. Malignant lymphomas of the thyroid: a clinical pathologic study of 35 patients including ultrastructural observations. Cancer 1977; 39: 1587–602

    Article  PubMed  CAS  Google Scholar 

  96. Isomaki HA, Hakulinen T, Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chron Dis 1978; 31: 691–6

    Article  PubMed  CAS  Google Scholar 

  97. Gridley G, McLaughlin JK, Ekborn A, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993; 85: 307–11

    Article  PubMed  CAS  Google Scholar 

  98. Katusic S, Beard CM, Kurland LT, et al. Occurrence of malignant neoplasms in the Rochester, Minnesota, rheumatoid arthritis cohort. Am J Med 1985; 79 Suppl. 1A: 50–5

    Article  Google Scholar 

  99. Prior P. Cancer and rheumatoid arthritis: epidemiologic considerations. Am J Med 1985; 78 Suppl. 1A: 15–21

    Article  PubMed  CAS  Google Scholar 

  100. Castor WC, Bull FE. Review of United States data on neoplasms in rheumatoid arthritis. Am J Med 1985; 78 Suppl. 1A: 33–8

    Article  PubMed  CAS  Google Scholar 

  101. Doody MM, Linet MS, Glass AG, et al. Leukemia, lymphoma and multiple myeloma following selected medical conditions. Cancer Causes Control 1992; 3: 449–56

    Article  PubMed  CAS  Google Scholar 

  102. Cibere J, Sibley J, Haga M. Rheumatoid arthritis and the risk of malignancy. Arthritis Rheum 1997; 40: 1580–6

    Article  PubMed  CAS  Google Scholar 

  103. Gridley G, Klippel JH, Hoover RN, et al. Incidence of cancer among men with the Felty syndrome. Ann Intern Med 1994; 120: 35–9

    PubMed  CAS  Google Scholar 

  104. Weisenberger DD. Epidemiology of non-Hodgkin’s lymphoma: recent findings regarding an emerging epidemic. Ann Oncol 1994; 5 Suppl. 1: S19–24

    Article  Google Scholar 

  105. Tugwell P, Pincus T, Yocum D, et al. Combination therapy with cyclosporin and methotrexate in severe rheumatoid arthritis. N Engl J Med 1995; 333: 137–41

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Medicine, Division of Rheumatic Diseases, The Hospital for Special Surgery, The New York Hospital, Cornell University Medical Center, New York, New York, NY 10021, USA

    Liviu Georgescu & Stephen A. Paget

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Georgescu, L., Paget, S.A. Lymphoma in Patients with Rheumatoid Arthritis. Drug-Safety 20, 475–487 (1999). https://doi.org/10.2165/00002018-199920060-00002

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