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Extended report
Lymphoma risk in systemic lupus: effects of disease activity versus treatment
  1. Sasha Bernatsky1,2,
  2. Rosalind Ramsey-Goldman3,
  3. Lawrence Joseph1,2,
  4. Jean-Francois Boivin2,
  5. Karen H Costenbader4,
  6. Murray B Urowitz5,
  7. Dafna D Gladman5,
  8. Paul R Fortin6,
  9. Ola Nived7,
  10. Michelle A Petri8,
  11. Soren Jacobsen9,
  12. Susan Manzi10,
  13. Ellen M Ginzler11,
  14. David Isenberg12,
  15. Anisur Rahman12,
  16. Caroline Gordon13,
  17. Guillermo Ruiz-Irastorza14,
  18. Edward Yelin15,
  19. Sang-Cheol Bae16,
  20. Daniel J Wallace17,
  21. Christine A Peschken18,
  22. Mary Anne Dooley19,
  23. Steven M Edworthy20,
  24. Cynthia Aranow21,
  25. Diane L Kamen22,
  26. Juanita Romero-Diaz23,
  27. Anca Askanase24,
  28. Torsten Witte25,
  29. Susan G Barr20,
  30. Lindsey A Criswell26,
  31. Gunnar K Sturfelt7,
  32. Irene Blanco27,
  33. Candace H Feldman4,
  34. Lene Dreyer28,
  35. Neha M Patel11,
  36. Yvan St Pierre1,
  37. Ann E Clarke1,2
  1. 1Medicine, Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Quebec, Canada
  2. 2Department of Medicine, McGill University, Montreal, Quebec, Canada
  3. 3Department of Medicine/Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  4. 4Medicine, Division of Rheumatology, Immunolog, Brigham and Women's Hospital, Boston, Massachusetts, USA
  5. 5Department of Medicine, Toronto Western Hospital, Toronto, Ontario, Canada
  6. 6Infectiologie et immunologie, Université de Laval, Quebec, Quebec, Canada
  7. 7Division of Rheumatology, Lund University Hospital, Lund, Sweden
  8. 8Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  9. 9Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  10. 10Department of Medicine, West Penn Allegheny Health System, Pittsburgh, Pennsylvania, USA
  11. 11Division of Rheumatology, Downstate Medical Centre, State University New York, Brooklyn, New York, USA
  12. 12Centre for Rheumatology Research, University College London, London, UK
  13. 13Rheumatology Research Group, University of Birmingham, Birmingham, UK
  14. 14Autoimmune Diseases Research Unit, Hospital Universitario Cruces, University of the Basque Country, Bizkaia, Spain
  15. 15Medicine, Division of Rheumatology, University of California, San Francisco, California, USA
  16. 16Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea
  17. 17Department of Medicine, Cedars-Sinai Medical Center/David Geffen School of Medicine at UCLA, Los Angeles, California, USA
  18. 18Medicine, Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  19. 19Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  20. 20Division of Rheumatology, University of Calgary, Calgary, Alberta, Canada
  21. 21Center for Autoimmune and Musculoskeletal, The Feinstein Institute for Medical Research, Manhasset, New York, USA
  22. 22Division of Immunology and Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA
  23. 23Division of Rheumatology and Immunology, Instituto Nacional de Cs Medicas y Nutricion, Mexico City, Mexico
  24. 24Department of Medicine, Hospital for Joint Diseases, New York University, New York, New York, USA
  25. 25Division of Immunology and Rheumatology, Hannover Medical School, Hannover, Germany
  26. 26Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, California, USA
  27. 27Division of Rheumatology, Albert Einstein College of Medicine, Bronx, New York, USA
  28. 28Department of Rheumatology, Rigshospitalet and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
  1. Correspondence to Dr Sasha Bernatsky, Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Royal Victoria Hospital, 687 Pine Avenue West, V-Building, Room V2.09 Montreal, Quebec, Canada H3A 1A1; sasha.bernatsky{at}


Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).

Methods We performed case–cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses.

Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls.

Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.

  • Systemic Lupus Erythematosus
  • Epidemiology
  • Treatment
  • Disease Activity

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