Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1987 May;55(5):523–529. doi: 10.1038/bjc.1987.107

A comparison of the incidence of the myelodysplastic syndrome and acute myeloid leukaemia following melphalan and cyclophosphamide treatment for myelomatosis. A report to the Medical Research Council's working party on leukaemia in adults.

J Cuzick, S Erskine, D Edelman, D A Galton
PMCID: PMC2001731  PMID: 3300761

Abstract

Twelve of 648 patients in the Medical Research Council's first two trials in myelomatosis have developed myelodysplasia or acute leukaemia. This corresponds to a 5-year actuarial prevalence of 3% and an 8-year prevalence of 10%. Patients were randomised to treatment with either melphalan or cyclophosphamide and the relative capabilities of these two drugs to cause these conditions were examined as a function of duration of treatment. A significant relationship with length of melphalan treatment was found but no relationship was observed for cyclophosphamide treatment. The amount of melphalan treatment given in various intervals before diagnosis of myelodysplasia or leukaemia was studied and it was found that the amount of treatment in the most recent 3-year period was the most important determinant of risk (P = 0.0001). It is estimated that the risk of haemopoietic neoplasia after 10 years of follow-up is about 3% for each year of melphalan treatment and that much of this risk will occur within three years of the last treatment.

Full text

PDF
528

Selected References

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

  1. Bennett J. M., Catovsky D., Daniel M. T., Flandrin G., Galton D. A., Gralnick H. R., Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189–199. [PubMed] [Google Scholar]
  2. Bergsagel D. E., Bailey A. J., Langley G. R., MacDonald R. N., White D. F., Miller A. B. The chemotherapy on plasma-cell myeloma and the incidence of acute leukemia. N Engl J Med. 1979 Oct 4;301(14):743–748. doi: 10.1056/NEJM197910043011402. [DOI] [PubMed] [Google Scholar]
  3. Berk P. D., Goldberg J. D., Silverstein M. N., Weinfeld A., Donovan P. B., Ellis J. T., Landaw S. A., Laszlo J., Najean Y., Pisciotta A. V. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med. 1981 Feb 19;304(8):441–447. doi: 10.1056/NEJM198102193040801. [DOI] [PubMed] [Google Scholar]
  4. 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]
  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. Casciato D. A., Scott J. L. Acute leukemia following prolonged cytotoxic agent therapy. Medicine (Baltimore) 1979 Jan;58(1):32–47. doi: 10.1097/00005792-197901000-00002. [DOI] [PubMed] [Google Scholar]
  7. Cuzick J. A method for analysing case-control studies with ordinal exposure variables. Biometrics. 1985 Sep;41(3):609–621. [PubMed] [Google Scholar]
  8. Gonzalez F., Trujillo J. M., Alexanian R. Acute leukemia in multiple myeloma. Ann Intern Med. 1977 Apr;86(4):440–443. doi: 10.7326/0003-4819-86-4-440. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Kyle R. A., Pierre R. V., Bayrd E. D. Multiple myeloma and acute myelomonocytic leukemia. N Engl J Med. 1970 Nov 19;283(21):1121–1125. doi: 10.1056/NEJM197011192832101. [DOI] [PubMed] [Google Scholar]
  11. Lakhani S., Davidson R. N., Hiwaizi F., Marsden R. A. Razoxane and leukaemia. Lancet. 1984 Aug 4;2(8397):288–289. doi: 10.1016/s0140-6736(84)90330-1. [DOI] [PubMed] [Google Scholar]
  12. Mufti G. J., Hamblin T. J., Clein G. P., Race C. Coexistent myelodysplasia and plasma cell neoplasia. Br J Haematol. 1983 May;54(1):91–96. doi: 10.1111/j.1365-2141.1983.tb02070.x. [DOI] [PubMed] [Google Scholar]
  13. Nowell P., Finan J. Chromosome studies in preleukemic states. IV. Myeloproliferative versus cytopenic disorders. Cancer. 1978 Nov;42(5):2254–2261. doi: 10.1002/1097-0142(197811)42:5<2254::aid-cncr2820420525>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  14. Pedersen-Bjergaard J., Larsen S. O. Incidence of acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome up to 10 years after treatment of Hodgkin's disease. N Engl J Med. 1982 Oct 14;307(16):965–971. doi: 10.1056/NEJM198210143071601. [DOI] [PubMed] [Google Scholar]
  15. Pedersen-Bjergaard J., Philip P., Pedersen N. T., Hou-Jensen K., Svejgaard A., Jensen G., Nissen N. I. Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. II. Bone marrow cytology, cytogenetics, results of HLA typing, response to antileukemic chemotherapy, and survival in a total series of 55 patients. Cancer. 1984 Aug 1;54(3):452–462. doi: 10.1002/1097-0142(19840801)54:3<452::aid-cncr2820540313>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  16. 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]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES