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. 1990 May;61(5):767–772. doi: 10.1038/bjc.1990.172

Prognostic significance of hepatotoxicity during maintenance chemotherapy for childhood acute lymphoblastic leukaemia.

K Schmiegelow 1, M Pulczynska 1
PMCID: PMC1971607  PMID: 2337515

Abstract

In a population-based study of 115 children with non-B-cell acute lymphoblastic leukaemia, we analysed the relation of the degree of leukopenia and risk of relapse to the degree of hepatotoxicity (as measured by serum aminotransferase (AT] during oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance chemotherapy (MT). Hepatotoxicity was calculated as a mean of all AT-measurements (mATMT). Lack of hepatotoxicity was defined as a mATMT less than or equal to 40 IUl-1. A highly significant correlation was demonstrated between the mean AT during the first, second, and third year of MT (r greater than 0.70, P less than 0.00001). mATMT was not related to the mean WBC during MT (r = -0.03, P = 0.36), but was related to the rise in WBC following cessation of therapy (r = 0.24, P = 0.06). Patients with recurrent disease had significantly lower mATMT than patients staying in remission (P = 0.03 for both over-all and haematological relapse risk). Patients with a mATMT greater than 40IUl-1 had a lower risk of relapse than patients with a mATMT less than or equal to 40IUl-1 (4.5 year CCR: 0.70 and 0.50, P = 0.06; and 4.5 year haematological remission: 0.83 and 0.63, P = 0.03). The favourable outcome for patients with hepatoxicity could be demonstrated for all risk groups.

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Selected References

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  1. Balis F. M., Holcenberg J. S., Zimm S., Tubergen D., Collins J. M., Murphy R. F., Gilchrist G. S., Hammond D., Poplack D. G. The effect of methotrexate on the bioavailability of oral 6-mercaptopurine. Clin Pharmacol Ther. 1987 Apr;41(4):384–387. doi: 10.1038/clpt.1987.45. [DOI] [PubMed] [Google Scholar]
  2. Harb J. M., Werlin S. L., Camitta B. M., Oechler H., Kamin B. A., Blank E. L. Hepatic ultrastructure in leukemic children treated with methotrexate and 6-mercaptopurine. Am J Pediatr Hematol Oncol. 1983 Winter;5(4):323–331. doi: 10.1097/00043426-198324000-00001. [DOI] [PubMed] [Google Scholar]
  3. Hendel J. Clinical pharmacokinetics of methotrexate in psoriasis therapy. Dan Med Bull. 1985 Dec;32(6):329–337. [PubMed] [Google Scholar]
  4. Lennard L., Lilleyman J. S. Are children with lymphoblastic leukaemia given enough 6-mercaptopurine? Lancet. 1987 Oct 3;2(8562):785–787. doi: 10.1016/s0140-6736(87)92511-6. [DOI] [PubMed] [Google Scholar]
  5. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966 Mar;50(3):163–170. [PubMed] [Google Scholar]
  6. McIntosh S., Davidson D. L., O'Brien R. T., Pearson H. A. Methotrexate hepatotoxicity in children with leukemia. J Pediatr. 1977 Jun;90(6):1019–1021. doi: 10.1016/s0022-3476(77)80587-8. [DOI] [PubMed] [Google Scholar]
  7. Ménard D. B., Gisselbrecht C., Marty M., Reyes F., Dhumeaux D. Antineoplastic agents and the liver. Gastroenterology. 1980 Jan;78(1):142–164. [PubMed] [Google Scholar]
  8. Nesbit M., Krivit W., Heyn R., Sharp H. Acute and chronic effects of methotrexate on hepatic, pulmonary, and skeletal systems. Cancer. 1976 Feb;37(2 Suppl):1048–1057. doi: 10.1002/1097-0142(197602)37:2+<1048::aid-cncr2820370811>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  9. Parker D., Bate C. M., Craft A. W., Graham-Pole J., Malpas J. S., Stansfeld A. G. Liver damage in children with acute leukaemia and non-Hodgkin's lymphoma on oral maintenance chemotherapy. Cancer Chemother Pharmacol. 1980;4(2):121–127. doi: 10.1007/BF00254033. [DOI] [PubMed] [Google Scholar]
  10. Peeters M., Koren G., Jakubovicz D., Zipursky A. Physician compliance and relapse rates of acute lymphoblastic leukemia in children. Clin Pharmacol Ther. 1988 Mar;43(3):228–232. doi: 10.1038/clpt.1988.25. [DOI] [PubMed] [Google Scholar]
  11. Poplack D. G., Balis F. M., Zimm S. The pharmacology of orally administered chemotherapy. A reappraisal. Cancer. 1986 Jul 15;58(2 Suppl):473–480. doi: 10.1002/1097-0142(19860715)58:2+<473::aid-cncr2820581311>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  12. Rodenhuis S., Kremer J. M., Bertino J. R. Increase of dihydrofolate reductase in peripheral blood lymphocytes of rheumatoid arthritis patients treated with low-dose oral methotrexate. Arthritis Rheum. 1987 Apr;30(4):369–374. doi: 10.1002/art.1780300402. [DOI] [PubMed] [Google Scholar]
  13. Simon R., Wittes R. E. Methodologic guidelines for reports of clinical trials. Cancer Treat Rep. 1985 Jan;69(1):1–3. [PubMed] [Google Scholar]
  14. Topley J. M., Benson J., Squier M. V., Chessells J. M. Hepatotoxicity in the treatment of acute lymphoblastic leukaemia. Med Pediatr Oncol. 1979;7(4):393–399. doi: 10.1002/mpo.2950070415. [DOI] [PubMed] [Google Scholar]
  15. Zimm S., Collins J. M., O'Neill D., Chabner B. A., Poplack D. G. Inhibition of first-pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol. Clin Pharmacol Ther. 1983 Dec;34(6):810–817. doi: 10.1038/clpt.1983.254. [DOI] [PubMed] [Google Scholar]
  16. Zimm S., Reaman G., Murphy R. F., Poplack D. G. Biochemical parameters of mercaptopurine activity in patients with acute lymphoblastic leukemia. Cancer Res. 1986 Mar;46(3):1495–1498. [PubMed] [Google Scholar]

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