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British Journal of Cancer logoLink to British Journal of Cancer
. 1987 Feb;55(2):213–218. doi: 10.1038/bjc.1987.40

Risk of leukaemia in ovarian tumour and breast cancer patients following treatment by cyclophosphamide.

J F Haas, B Kittelmann, W H Mehnert, W Staneczek, M Möhner, J M Kaldor, N E Day
PMCID: PMC2002085  PMID: 3814491

Abstract

A case-control study was conducted to determine whether the development of leukaemia was associated with chemotherapy for neoplasms of the ovary or breast, in a population where most such chemotherapy consisted of cyclophosphamide alone. Cases and controls were identified from the National Cancer Registry of the German Democratic Republic. Cases were women who had developed leukaemia as a second primary after an initial diagnosis, at least one year before, of an ovarian or breast tumour. Controls were patients with an ovarian tumour or breast cancer who had survived to the year when the case developed a leukaemia but who had not themselves developed a second malignancy. Controls were matched to cases by the site of the first primary and its year of diagnosis, as well as year of birth. The relative risk for acute leukaemia following treatment with cyclophosphamide alone was significantly elevated (P less than 0.05), at 14.6 for ovarian tumour patients and 2.7 for breast cancer patients. Among breast cancer patients the increased risk of leukaemia associated with chemotherapy was confined to women who had been under 50 years of age at the time of diagnosis of the breast cancer (for whom the relative risk was 13.1). No excess risk of leukaemia was observed in association with radiotherapy for either ovarian or breast cancer patients. The present findings strongly suggest that cyclophosphamide as a single chemotherapeutic agent is capable of inducing leukaemia in humans.

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Selected References

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

  1. Boice J. D., Hutchison G. B. Leukemia in women following radiotherapy for cervical cancer: ten-year follow-up of an international study. J Natl Cancer Inst. 1980 Jul;65(1):115–129. [PubMed] [Google Scholar]
  2. Boice J. D., Jr, Day N. E., Andersen A., Brinton L. A., Brown R., Choi N. W., Clarke E. A., Coleman M. P., Curtis R. E., Flannery J. T. Second cancers following radiation treatment for cervical cancer. An international collaboration among cancer registries. J Natl Cancer Inst. 1985 May;74(5):955–975. [PubMed] [Google Scholar]
  3. Boice J. D., Jr, Greene M. H., Killen J. Y., Jr, Ellenberg S. S., Keehn R. J., McFadden E., Chen T. T., Fraumeni J. F., Jr Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU). N Engl J Med. 1983 Nov 3;309(18):1079–1084. doi: 10.1056/NEJM198311033091802. [DOI] [PubMed] [Google Scholar]
  4. Brody R. S., Schottenfeld D., Reid A. Multiple primary cancer risk after therapy for Hodgkin's disease. Cancer. 1977 Oct;40(4 Suppl):1917–1926. doi: 10.1002/1097-0142(197710)40:4+<1917::aid-cncr2820400824>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  5. Buckman R., Cuzick J., Galton D. A. Long-term survival in myelomatosis. A report to the MRC working party on leukaemia in adults. Br J Haematol. 1982 Dec;52(4):589–599. doi: 10.1111/j.1365-2141.1982.tb03935.x. [DOI] [PubMed] [Google Scholar]
  6. Einhorn N. Acute leukemia after chemotherapy (melphalan). Cancer. 1978 Feb;41(2):444–447. doi: 10.1002/1097-0142(197802)41:2<444::aid-cncr2820410210>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  7. Einhorn N., Eklund G., Franzén S., Lambert B., Lindsten J., Söderhäll S. Late side effects of chemotherapy in ovarian carcinoma: a cytogenetic, hematologic, and statistical study. Cancer. 1982 Jun 1;49(11):2234–2241. doi: 10.1002/1097-0142(19820601)49:11<2234::aid-cncr2820491106>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  8. Elliott R. W., Essenhigh D. M., Morley A. R. Cyclophosphamide treatment of systemic lupus erythematosus: risk of bladder cancer exceeds benefit. Br Med J (Clin Res Ed) 1982 Apr 17;284(6323):1160–1161. doi: 10.1136/bmj.284.6323.1160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fisher B., Rockette H., Fisher E. R., Wickerham D. L., Redmond C., Brown A. Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience. J Clin Oncol. 1985 Dec;3(12):1640–1658. doi: 10.1200/JCO.1985.3.12.1640. [DOI] [PubMed] [Google Scholar]
  10. Greene M. H., Boice J. D., Jr, Greer B. E., Blessing J. A., Dembo A. J. Acute nonlymphocytic leukemia after therapy with alkylating agents for ovarian cancer: a study of five randomized clinical trials. N Engl J Med. 1982 Dec 2;307(23):1416–1421. doi: 10.1056/NEJM198212023072302. [DOI] [PubMed] [Google Scholar]
  11. Greene M. H., Harris E. L., Gershenson D. M., Malkasian G. D., Jr, Melton L. J., 3rd, Dembo A. J., Bennett J. M., Moloney W. C., Boice J. D., Jr Melphalan may be a more potent leukemogen than cyclophosphamide. Ann Intern Med. 1986 Sep;105(3):360–367. doi: 10.7326/0003-4819-105-3-360. [DOI] [PubMed] [Google Scholar]
  12. Grünwald H. W., Rosner F. Acute leukemia and immunosupressive drug use: a review of patients undergoing immunosuppressive therapy for non-neoplastic diseases. Arch Intern Med. 1979 Apr;139(4):461–466. [PubMed] [Google Scholar]
  13. Pedersen-Bjergaard J., Ersbøll J., Sørensen H. M., Keiding N., Larsen S. O., Philip P., Larsen M. S., Schultz H., Nissen N. I. Risk of acute nonlymphocytic leukemia and preleukemia in patients treated with cyclophosphamide for non-Hodgkin's lymphomas. Comparison with results obtained in patients treated for Hodgkin's disease and ovarian carcinoma with other alkylating agents. Ann Intern Med. 1985 Aug;103(2):195–200. doi: 10.7326/0003-4819-103-2-195. [DOI] [PubMed] [Google Scholar]
  14. Plotz P. H., Klippel J. H., Decker J. L., Grauman D., Wolff B., Brown B. C., Rutt G. Bladder complications in patients receiving cyclophosphamide for systemic lupus erythematosus or rheumatoid arthritis. Ann Intern Med. 1979 Aug;91(2):221–223. doi: 10.7326/0003-4819-91-2-221. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Schmähl D., Habs M. Carcinogenic action of low-dose cyclophosphamide given orally to Sprague-Dawley rats in a lifetime experiment. Int J Cancer. 1979 May 15;23(5):706–712. doi: 10.1002/ijc.2910230518. [DOI] [PubMed] [Google Scholar]

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