Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1983 Oct;48(4):559–567. doi: 10.1038/bjc.1983.229

Quantitation of chemosensitivity in acute myelocytic leukaemia.

M G Lihou, P J Smith
PMCID: PMC2011489  PMID: 6578837

Abstract

A system for the prediction of clinical response in acute myelocytic leukaemia (AML), based on inhibition of growth of colony forming cells (CFC) was studied. If the product of initial drug concentration and time of exposure (C X T) was constant, the response to adriamycin (Adr) was constant, at T values less than 48 h. No constancy of response to the phase-specific agents cytosine arabinoside (Ara-C) and 6-thioguanine (6TG) was demonstrated with constant C X T (T value range 0.25-48 h). Hence in the predictive test, a 1 h incubation with Adr was employed whilst a continuous exposure to Ara-C and 6TG, with these drugs incorporated in the agar medium, was used. The in vitro sensitivity to Adr, Ara-C and 6TG of 19 AML patients and the predictive value of several parameters of sensitivity were evaluated. 6TG sensitivity was not useful for prediction of remission. Adr sensitivity in vitro made a greater contribution to prediction of remission than did Ara-C sensitivity. Seventy-nine percent of patients were correctly classified if Adr data alone were considered. A multivariate function including Adr and Ara-C results was obtained which resulted in 84% of patients correctly classified as sensitive or resistant to the agents received in remission-induction therapy.

Full text

PDF
559

Selected References

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

  1. Bertoncello I., Bradley T. R. The physicochemical properties of erythrocyte derived activity which enhances murine bone marrow colony growth in agar culture. Aust J Exp Biol Med Sci. 1977 Jun;55(3):281–292. doi: 10.1038/icb.1977.23. [DOI] [PubMed] [Google Scholar]
  2. Bodey G. P., Rodriguez V. Approaches to the treatment of acute leukemia and lymphoma in adults. Semin Hematol. 1978 Jul;15(3):221–261. [PubMed] [Google Scholar]
  3. Burgess A. W., Wilson E. M., Metcalf D. Stimulation by human placental conditioned medium of hemopoietic colony formation by human marrow cells. Blood. 1977 Apr;49(4):573–583. [PubMed] [Google Scholar]
  4. Burgoyne L. A. Effect of cytosine arabinoside triphosphate on deoxyribonucleic acid synthesis in permealysed cells from Ehrlich ascites tumour. Studies of phosphorylated drub metabolites on quasi-normal deoxyribonucleic acid replication. Biochem Pharmacol. 1974 May 1;23(11):1619–1627. doi: 10.1016/0006-2952(74)90374-8. [DOI] [PubMed] [Google Scholar]
  5. Dooley T., Maddocks J. L. Assay of 6-thioguanine in human plasma. Br J Clin Pharmacol. 1980 Jan;9(1):77–82. doi: 10.1111/j.1365-2125.1980.tb04800.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eichholtz H., Trott K. R. Effect of methotrexate concentration and exposure time on mammalian cell survival in vitro. Br J Cancer. 1980 Feb;41(2):277–284. doi: 10.1038/bjc.1980.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gale R. P., Cline M. J. High remission-induction rate in acute myeloid leukaemia. Lancet. 1977 Mar 5;1(8010):497–499. doi: 10.1016/s0140-6736(77)91366-6. [DOI] [PubMed] [Google Scholar]
  8. Harris P. A., Gross J. F. Preliminary pharmacokinetic model for adriamycin (NSC-123127). Cancer Chemother Rep. 1975 Jul-Aug;59(4):819–825. [PubMed] [Google Scholar]
  9. LePage G. A., Whitecar J. P., Jr Pharmacology of 6-thioguanine in man. Cancer Res. 1971 Nov;31(11):1627–1631. [PubMed] [Google Scholar]
  10. McCulloch E. A., Buick R. N., Curtis J. E., Messner H. A., Senn J. S. The heritable nature of clonal characteristics in acute myeloblastic leukemia. Blood. 1981 Jul;58(1):105–109. [PubMed] [Google Scholar]
  11. McCulloch E. A., Curtis J. E., Messner H. A., Senn J. S., Germanson T. P. The contribution of blast cell properties to outcome variation in acute myeloblastic leukemia (AML). Blood. 1982 Mar;59(3):601–608. [PubMed] [Google Scholar]
  12. Meyskens F. L., Jr, Moon T. E., Dana B., Gilmartin E., Casey W. J., Chen H. S., Franks D. H., Young L., Salmon S. E. Quantitation of drug sensitivity by human metastatic melanoma colony-forming units. Br J Cancer. 1981 Dec;44(6):787–797. doi: 10.1038/bjc.1981.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moon T. E., Salmon S. E., White C. S., Chen H. S., Meyskens F. L., Durie B. G., Alberts D. S. Quantitative association between the in vitro human tumor stem cell assay and clinical response to cancer chemotherapy. Cancer Chemother Pharmacol. 1981;6(3):211–218. doi: 10.1007/BF00256973. [DOI] [PubMed] [Google Scholar]
  14. Park C. H., Amare M., Savin M. A., Goodwin J. W., Newcomb M. M., Hoogstraten B. Prediction of chemotherapy response in human leukemia using an in vitro chemotherapy sensitivity test on the leukemic colony-forming cells. Blood. 1980 Apr;55(4):595–601. [PubMed] [Google Scholar]
  15. Preisler H. D. Prediction of response to chemotherapy in acute myelocytic leukemia. Blood. 1980 Sep;56(3):361–367. [PubMed] [Google Scholar]
  16. Salmon S. E., Alberts D. S., Meyskens F. L., Jr, Durie B. G., Jones S. E., Soehnlen B., Young L., Chen H. S., Moon T. E. Clinical correlations of in vitro drug sensitivity. Prog Clin Biol Res. 1980;48:223–245. [PubMed] [Google Scholar]
  17. Salmon S. E., Hamburger A. W., Soehnlen B., Durie B. G., Alberts D. S., Moon T. E. Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. N Engl J Med. 1978 Jun 15;298(24):1321–1327. doi: 10.1056/NEJM197806152982401. [DOI] [PubMed] [Google Scholar]
  18. Sheridan J. W., Simmons R. J. Studies on a human melanoma cell line: effect of cell crowding and nutrient depletion on the biophysical and kinetic characteristics of the cells. J Cell Physiol. 1981 Apr;107(1):85–100. doi: 10.1002/jcp.1041070111. [DOI] [PubMed] [Google Scholar]
  19. Wu P. C., Ozols R. F., Hatanaka M., Boone C. W. Anticancer drugs: effect on the cloning of Raji lymphoma cells in soft agar. J Natl Cancer Inst. 1982 Jan;68(1):115–121. [PubMed] [Google Scholar]

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

RESOURCES