Erythrocyte concentrations of metabolites or cumulative doses of 6-mercaptopurine and methotrexate do not predict liver changes in children treated for acute lymphoblastic leukemia

Pediatric Blood and Cancer

Volumn 46, Issue 7, 2006, Pages 762-766

  Halonen, Päivi ^a,b   Mattila, Jorma ^b   Mäkipernaa, Anne ^c   Ruuska, Tarja ^d   Schmiegelow, Kjeld ^b  

^a TAMPERE UNIVERSITY OF TECHNOLOGY   (Finland)

^b TAMPERE UNIVERSITY HOSPITAL   (Finland)

^c FINNISH RED CROSS BLOOD SERVICE   (Finland)

^d Rigshospitalet   (Denmark)

Author keywords

Acute lymphoblastic leukemia; Hepatotoxicity; Mercaptopurine; Methotrexate

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARAGINASE; DEXAMETHASONE; DOXORUBICIN; DRUG METABOLITE; FOLINIC ACID; MERCAPTOPURINE; METHOTREXATE; PREDNISOLONE; VINCRISTINE;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADOLESCENT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CHILD; CLINICAL ARTICLE; DRUG ACCUMULATION; DRUG ERYTHROCYTE LEVEL; DRUG MEGADOSE; FATTY LIVER; FEMALE; HISTOPATHOLOGY; HUMAN; LEUKOCYTE COUNT; LIVER BIOPSY; LIVER FIBROSIS; LIVER TOXICITY; MAINTENANCE THERAPY; MALE; PRIORITY JOURNAL; STATISTICAL ANALYSIS;

6-MERCAPTOPURINE; ADOLESCENT; ANTIMETABOLITES, ANTINEOPLASTIC; BIOLOGICAL MARKERS; CHILD; CHILD, PRESCHOOL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG MONITORING; ERYTHROCYTES; FEMALE; HEPATITIS, TOXIC; HUMANS; LEUKEMIA, LYMPHOCYTIC, ACUTE, L1; LIVER CIRRHOSIS; MALE; METHOTREXATE; STATISTICS, NONPARAMETRIC;

EID: 33646543307     PISSN: 15455009     EISSN: 15455017     Source Type: Journal    
DOI: 10.1002/pbc.20442     Document Type: Article

References (26)

1. Einhorn M, Davidsohn I. Hepatotoxicity of mercaptopurine. JAMA 1964;188:802-806.
2. Shorey J, Schenker S, Suki WN, et al. Hepatotoxicity of mercaptopurine. Arch Intern Med 1968;122:54-58.
3. Colsky J, Greenspan EM, Warren TN. Hepatic fibrosis in children with acute lymphoblastic leukemia after therapy with folic acid antagonists. Arch Pathol Lab Med 1955;59:198-206.
4. Hutter RVP, Shipkey FH, Tan CTC, et al. Hepatic fibrosis in children with acute leukemia. Cancer 1960;13:288-307.
5. McIntosh S, Davidson DL, O'Brien RT, et al. Methotrexate hepatotoxicity in children with leukemia. J pediatr 1977;90:1019-1021.
6. Parker D, Bate CM, Craft AW, et al. Liver damage in children with acute leukaemia and non-Hodgkin's lymphoma on oral maintenance chemotherapy. Cancer Chemother Pharniacol 1980;4:121-127.
7. Ruymann FB, Mosijczuk AD, Sayers RJ. Hepatoma in a child with methotrexate-induced hepatic fibrosis. JAMA 1977;238:2631-2633.
8. Dahl MG, Gregory MM, Scheuer PJ. Methotrexate hepatotoxicity in psoriasis-comparison of different dose regimens. Br Med J 1972;1:654-656.
9. Zachariae H, Sogaard H. Methotrexate-induced liver cirrhosis. A follow-up. Dermatological 1987;175:178-182.
10. Kremer JM, Lee RG, Tolman KG. Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. Arthritis Rheum 1989;32:121-127.
11. King PD, Perry MC. Hepatotoxicity of chemotherapy. Oncologist 2001;6:162-176.
12. Craft AW, Rankin A, Aherne W. Methotrexate absorption in children with acute lymphoblastic leukemia. Cancer Treat Rep 1981;65:77-81.
13. Lennard L, Lilleyman JS. Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia. J Clin Oncol 1989;7:1816-1823.
14. Scmiegelow K, Schroder H, Gustafsson G, et al. Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. J Clin Oncol 1995;13:345-35 1.
15. Schmiegelow K, Schroder H, Schmiegelow M. Methotrexate and 6-mercaptopurine maintenance therapy for childhood acute lymphoblastic leukaemia: Dose adjustments by white cell counts or by pharmacokinetic parameters? Cancer Chemother Pharmacol 1994;34:209-215.
16. Tidd DM, Patersson ARP. A biochemical mechanism for the delayed cytotoxic action of 6-mercaptopurine. Cancer Res 1974;34:738-746.
17. Chabner BA, Allegra CJ, Curt GA, et al. Polyglutamation of methotrexate: Is methotreaxte a prodrug? J Clin Invest 1985;76:907-912.
18. Gustafsson G, Kreuger A, Clausen N, et al. Intensified treatment of childhood acute lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: The Nordic experience of 2648 patients diagnosed between 1981 and 1996. Acta Paediatr 1998;87:1151-1161.
19. Bruunshuus I, Schmiegelow K. Analysis of 6-mercaptopurine, 6-thioguanine nucleotides, and 6-thiouric acid in biological fluids by high-performance liquid chromatography. Scand J Clin Invest 1989;49:779-784.
20. Kamen BA, Takach PL, Valev R, et al. A rapid radiochemical-ligand binding assay for methotrexate. Anal Biochem 1976;70:54-63.
21. Scheuer PJ. Classification of chronic viral hepatitis, a need for reassessment. J Hepatol 1991;13:372-374.
22. Deugnier YM, Turlin B, Powell LW, et al. Differentiation between heterozygotes and homozygotes in genetic hemochromatosis by means of histological hepatic iron index: A study of 192 cases. Hepatology 1993;17:30-34.
23. Schmiegelow K, Schroder H, Pulczynska MK, et al. Maintenance chemotherapy for childhood acute lymphoblastic leukemia: Relation of bone-marrow and hepatotoxicity to the concentration of methotrexate in crythrocytes. Cancer Chemother Pharmacol 1989;25:65-69.
24. Nygaard U, Toft N, Schmiegelow K. Methylated metabolites of 6-mercaptopurine are associated with hepatotoxicity. Clin Pharmacol Ther 2004;75:274-281.
25. Brick JE, Morelund LW, Al-Kawas F, et al. Prospective analysis of liver biopsies before and after methotrexate therapy in rheumatoid patients. Semin Arthritis Rheum 1989;19:31-44.
26. Hashkes PJ, Balistreri WF, Bove KE, et al. The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis. J Pediatr 1999;134:47-52.