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. 1983 Aug;42(4):368–373. doi: 10.1136/ard.42.4.368

The occurrence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide: a controlled retrospective follow-up.

J A Baltus, J W Boersma, A P Hartman, J P Vandenbroucke
PMCID: PMC1001244  PMID: 6882031

Abstract

In a retrospective follow-up we compared the incidence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide with that in another group of patients with rheumatoid arthritis and also with the incidence of malignancies in the general population. Among 81 patients treated with cyclophosphamide in the past decade 15 malignancies occurred. This was 4.1 times the expected number obtained from a closely matched control group of patients with rheumatoid arthritis not treated with cytotoxic drugs (95% confidence interval 1.5 to 19.0), and 3.7 times the expected number calculated from general population rates (95% confidence interval 2.1 to 5.9). The increase in haematological and lymphoreticular malignancies was specially notable. The data also indicate that the development of malignancies after the start of cyclophosphamide therapy necessitates a certain induction time and that it is to some extent dose-dependent.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auclerc G., Jacquillat C., Auclerc M. F., Weil M., Bernard J. Post-therapeutic acute leukemia. Cancer. 1979 Dec;44(6):2017–2025. doi: 10.1002/1097-0142(197912)44:6<2017::aid-cncr2820440609>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  2. Banks P. M., Witrak G. A., Conn D. L. Lymphoid neoplasia following connective tissue disease. Mayo Clin Proc. 1979 Feb;54(2):104–108. [PubMed] [Google Scholar]
  3. COBB S., ANDERSON F., BAUER W. Length of life and cause of death in rheumatoid arthritis. N Engl J Med. 1953 Oct 1;249(14):553–556. doi: 10.1056/NEJM195310012491402. [DOI] [PubMed] [Google Scholar]
  4. Calabro J. J. Cancer and arthritis. Arthritis Rheum. 1967 Dec;10(6):553–567. doi: 10.1002/art.1780100608. [DOI] [PubMed] [Google Scholar]
  5. Currey H. L., Harris J., Mason R. M., Woodland J., Beveridge T., Roberts C. J., Vere D. W., Dixon A. S., Davies J., Owen-Smith B. Comparison of azathioprine, cyclophosphamide, and gold in treatment of rheumatoid arthritis. Br Med J. 1974 Sep 28;3(5934):763–766. doi: 10.1136/bmj.3.5934.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cytotoxic drugs in treatment of nonmalignant diseases. Ann Intern Med. 1972 Apr;76(4):619–642. doi: 10.7326/0003-4819-76-4-619. [DOI] [PubMed] [Google Scholar]
  7. DUTHIE J. J., BROWN P. E., TRUELOVE L. H., BARAGAR F. D., LAWRIE A. J. COURSE AND PROGNOSIS IN RHEUMATOID ARTHRITIS. A FURTHER REPORT. Ann Rheum Dis. 1964 May;23:193–204. doi: 10.1136/ard.23.3.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis J. D., Muss H. B., Turner R. A. Cytotoxic agents in the treatment of rheumatoid arthritis. South Med J. 1978 Jan;71(1):58–64. doi: 10.1097/00007611-197801000-00016. [DOI] [PubMed] [Google Scholar]
  9. Fosdick W. M., Parsons J. L., Hill D. F. Long-term cyclophosphamide therapy in rheumatoid arthritis. Arthritis Rheum. 1968 Apr;11(2):151–161. doi: 10.1002/art.1780110205. [DOI] [PubMed] [Google Scholar]
  10. Goldenberg G. J., Paraskevas F., Israels L. G. The association of rheumatoid arthritis with plasma cell and lymphocytic neoplasms. Arthritis Rheum. 1969 Dec;12(6):569–579. doi: 10.1002/art.1780120604. [DOI] [PubMed] [Google Scholar]
  11. Isomäki H. A., Hakulinen T., Joutsenlahti U. Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis. 1978;31(11):691–696. doi: 10.1016/0021-9681(78)90071-1. [DOI] [PubMed] [Google Scholar]
  12. Isomäki H. A., Mutru O., Koota K. Death rate and causes of death in patients with rheumatoid arthritis. Scand J Rheumatol. 1975;4(4):205–208. doi: 10.3109/03009747509165257. [DOI] [PubMed] [Google Scholar]
  13. Kahn M. F., Arlet J., Bloch-Michel H., Caroit M., Chaouat Y., Renier J. C. Leucémies aiguës après traitement par agents cytotoxiques en rhumatologie. 19 observations chez 2006 patients. Nouv Presse Med. 1979 Apr 14;8(17):1393–1397. [PubMed] [Google Scholar]
  14. Kent P. The slow miracle. Br Med J (Clin Res Ed) 1981 Jun 20;282(6281):2029–2030. doi: 10.1136/bmj.282.6281.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kinlen L. J., Sheil A. G., Peto J., Doll R. Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs. Br Med J. 1979 Dec 8;2(6203):1461–1466. doi: 10.1136/bmj.2.6203.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Konttinen Y. T., Reitamo S., Ranki A., Häyry P., Kankaanapä U., Wegelius O. Characterization of the immunocompetent cells of rheumatoid synovium from tissue sections and eluates. Arthritis Rheum. 1981 Jan;24(1):71–79. doi: 10.1002/art.1780240112. [DOI] [PubMed] [Google Scholar]
  17. Lewis R. B., Castor C. W., Knisley R. E., Bole G. G. Frequency of neoplasia in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 1976 Nov-Dec;19(6):1256–1260. doi: 10.1002/art.1780190605. [DOI] [PubMed] [Google Scholar]
  18. Love R. R., Sowa J. M. Myelomonocytic leukaemia following cyclophosphamide therapy of rheumatoid disease. Ann Rheum Dis. 1975 Dec;34(6):534–535. doi: 10.1136/ard.34.6.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller D. G. The association of immune disease and malignant lymphoma. Ann Intern Med. 1967 Mar;66(3):507–521. doi: 10.7326/0003-4819-66-3-507. [DOI] [PubMed] [Google Scholar]
  20. Monson R. R., Hall A. P. Mortality among arthritics. J Chronic Dis. 1976 Jul;29(7):459–467. doi: 10.1016/0021-9681(76)90086-2. [DOI] [PubMed] [Google Scholar]
  21. Mutru O., Koota K., Isomäki H. Causes of death in autopsied RA patients. Scand J Rheumatol. 1976;5(4):239–240. doi: 10.3109/03009747609099912. [DOI] [PubMed] [Google Scholar]
  22. Oleinick A. Leukemia or lymphoma occurring subsequent to an autoimmune disease. Blood. 1967 Jan;29(1):144–153. [PubMed] [Google Scholar]
  23. Penn I. Malignancies associated with immunosuppressive or cytotoxic therapy. Surgery. 1978 May;83(5):492–502. [PubMed] [Google Scholar]
  24. Penn I. Second malignant neoplasms associated with immunosuppressive medications. Cancer. 1976 Feb;37(2 Suppl):1024–1032. doi: 10.1002/1097-0142(197602)37:2+<1024::aid-cncr2820370806>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  25. Penn I., Starzl T. E. Immunosuppression and cancer. Transplant Proc. 1973 Mar;5(1):943–947. [PMC free article] [PubMed] [Google Scholar]
  26. Pirofsky B., Bardana E. J., Jr Immunosuppressive therapy in rheumatic disease. Med Clin North Am. 1977 Mar;61(2):419–437. doi: 10.1016/s0025-7125(16)31342-6. [DOI] [PubMed] [Google Scholar]
  27. Prieur A. M., Balafrej M., Griscelli C., Mozziconacci P. Résultats et risques à long terme des traitements immunosuppresseurs dans l'arthrite chronique juvénile. A propos de 40 observations. Rev Rhum Mal Osteoartic. 1979 Feb;46(2):85–90. [PubMed] [Google Scholar]
  28. Puri H. C., Campbell R. A. Cyclophosphamide and malignancy. Lancet. 1977 Jun 18;1(8025):1306–1306. doi: 10.1016/s0140-6736(77)91336-8. [DOI] [PubMed] [Google Scholar]
  29. Reimer R. R., Hoover R., Fraumeni J. F., Jr, Young R. C. Acute leukemia after alkylating-agent therapy of ovarian cancer. N Engl J Med. 1977 Jul 28;297(4):177–181. doi: 10.1056/NEJM197707282970402. [DOI] [PubMed] [Google Scholar]
  30. Renier J. C., Bregeon C., Bonnette C., Boasson M., Bernat M., Basle M., Besson J., Wellinger C., Bourgeois B., Teisseire N. Le devenir des sujets atteints de polyarthrite rhumatoïde et traités par les immunodépresseurs entre 1965 et 1973 inclus. Rev Rhum Mal Osteoartic. 1978 Jul-Sep;45(7-9):453–461. [PubMed] [Google Scholar]
  31. Seidenfeld A. M., Smythe H. A., Ogryzlo M. A., Urowitz M. B., Dotten D. A. Acute leukemia in rheumatoid arthritis treated with cytotoxic agents. J Rheumatol. 1976 Sep;3(3):295–304. [PubMed] [Google Scholar]
  32. Stojanović I., Budimir M., Nikolić J., Maksimović B., Berović Z. Duration of improvement of rheumatoid arthritis after good response to cyclophosphamide treatment. Scand J Rheumatol. 1978;7(1):1–2. [PubMed] [Google Scholar]
  33. Tannenbaum H., Schur P. H. Development of reticulum cell sarcoma during cyclophosphamide therapy. Arthritis Rheum. 1974 Jan-Feb;17(1):15–18. doi: 10.1002/art.1780170104. [DOI] [PubMed] [Google Scholar]
  34. Townes A. S., Sowa J. M., Shulman L. E. Controlled trial of cyclophosphamide in rheumatoid arthritis. Arthritis Rheum. 1976 May-Jun;19(3):563–573. doi: 10.1002/art.1780190308. [DOI] [PubMed] [Google Scholar]
  35. Uddin J., Kraus A. S., Kelly H. G. Survivorship and death in rheumatoid arthritis. Arthritis Rheum. 1970 Mar-Apr;13(2):125–130. doi: 10.1002/art.1780130204. [DOI] [PubMed] [Google Scholar]
  36. Wall R. L., Clausen K. P. Carcinoma of the urinary bladder in patients receiving cyclophosphamide. N Engl J Med. 1975 Aug 7;293(6):271–273. doi: 10.1056/NEJM197508072930604. [DOI] [PubMed] [Google Scholar]
  37. Williams H. J., Reading J. C., Ward J. R., O'Brien W. M. Comparison of high and low dose cyclophosphamide therapy in rheumatoid arthritis. Arthritis Rheum. 1980 May;23(5):521–527. doi: 10.1002/art.1780230502. [DOI] [PubMed] [Google Scholar]

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