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Pediatric Inflammatory Bowel Disease pp 371–378Cite as

6-Mercaptopurine Therapy

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References

  1. Tiede I, Fritz G, Strand S. et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 2003;111:1122–4.

    Article  CAS  Google Scholar 

  2. Carvalho RS, Mahoney JA, Oliva-Hemker MM, et al. Inherent resistance to 6-thioguanine induced apoptosis correlates with disease activity in children with IBD. Gastroenterology 2006;A203.

    Google Scholar 

  3. Markowitz J, Rosa J, Grancher K, Aiges H, Daum F. Long-term 6-mercaptopurine treatment in adolescents with Crohn’s disease. Gastroenterology 1990;99:1347–51.

    PubMed  CAS  Google Scholar 

  4. Verhave M, Winter HS, Grand RJ. Azathioprine in the treatment of children with inflammatory bowel disease. J Pediatr 1990;117:809–14.

    Article  PubMed  CAS  Google Scholar 

  5. Markowitz J, Grancher K, Mandel F, Daum F. Immunosuppressive therapy in pediatric inflammatory bowel disease: results of a survey of the North American Society for pediatric Gastroenterology and Nutrition. Subcommittee on immunosuppressive use of the pediatric IBD collaborative research forum. Am J Gastroenterol 1993;88:44–8.

    PubMed  CAS  Google Scholar 

  6. Present DH, Meltzer SJ, Krumholz MP, et al. 6-mercaptopurine in the management of inflammatory bowel disease: short and long-term toxicity. Ann Intern Med 1995;111:641–9.

    Google Scholar 

  7. Weinshilboum RN, Sladek Sl. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyl transferase activity. Am J Hum Genet 1980;32:651–62.

    PubMed  CAS  Google Scholar 

  8. Pearson DC, May GR, Fick GH, Sutherland SR. Azathioprine and 6-mercaptopurine in Crohn’s disease: a meta-analysis. Ann Intern Med 1995;122:132–42.

    Google Scholar 

  9. Markowitz J, Hyams J, Mack D. et al. Corticosteroid therapy in the age of infliximab: Acute and 1-year outcomes in newly diagnosed children with crohn’s disease. Clin Gastroenterol Hepatol. Ann2006;4:1124–29.

    Google Scholar 

  10. Markowitz J, Grancher K, Kohn N, et.al. A multi-center trial of 6-mercaptopurine and prednisone therapy in children with newly diagnosed Crohn’s disease. Gastroenterology 2000;119:895–902.

    Article  PubMed  CAS  Google Scholar 

  11. Camma C, Giunta M, Rosselli M, Cottone M. Mesalamine in the maintenance treatment of Crohn’s disease: a meta-analysis adjusted for confounding variables. Gastroenterology 1997;113:1465–73.

    Article  PubMed  CAS  Google Scholar 

  12. Brant SR, Panhuysen CI, Bailey-Wilson JE, et al. Linkage heterogeneity for the IBD1 locus in Crohn’s disease pedigrees by disease onset and severity. Gastroenterology. Ann2000;119:1483–90.

    Google Scholar 

  13. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCECT I randomized trial. Lancet 2002;359:1541–9.

    Article  PubMed  CAS  Google Scholar 

  14. Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology 1999;117:761–9

    Article  PubMed  CAS  Google Scholar 

  15. Hommes D, Baert F, Van Assche G, et al. The ideal management of Crohn’s disease: top down versus step up strategies, a randomized control trial. Gastroenterology 2006;A108.

    Google Scholar 

  16. Siegel CA, Hur C, Korzenik JR, et al. Risks and Benefits of Infliximab for the Treatment of Crohn’s Disease. Clin Gastroenterol Hepatol 2006;8:1017–24.

    Article  CAS  Google Scholar 

  17. Thayu M, Markowitz JE, Mamula P, et al. Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn disease. J Pediatr Gastroenterol Nutr 2005;2:220–2.

    Google Scholar 

  18. Mamula P, Markowitz JE, Cohen LJ, et al. Infliximab in pediatric ulcerative colitis: two-year follow-up. J Pediatr Gastroenterol Nutr 2004;38(3):298–301.

    Article  PubMed  CAS  Google Scholar 

  19. Baldassano RN, Han PD, Jeshion WC, et al. Pediatric Crohn’s disease: risk factors for postoperative recurrence. Am J Gastroenterol 2001;7:2169–76.

    Article  Google Scholar 

  20. Hanauer SB, Korelitz BI, Rutgeerts P, et al. Post-operative maintenance of Crohn’s disease remission with 6-mercaptopurine, mesalamine or placebo: a 2 year trial. Gastroenterology 2004;127:723–9.

    Article  PubMed  CAS  Google Scholar 

  21. Ewe K, Press AG, Singe CC, et al. Azathioprine combined with prednisolone or monotherapy with prednisolone in active Crohn’s disease. Gastroenterology 1993;105:367–72.

    PubMed  CAS  Google Scholar 

  22. Candy S, Wright J, Gerber M, Adams G, Gerig M, Goodman R. A controlled double blind study of azathioprine in the management of Crohn’s disease Gut. Ann1995;37:674–78.

    Google Scholar 

  23. Korelitz BI, Adler DJ, Mendelsohn RA, et al. Long-term experience with 6-mercaptopurine in the treatment of Crohn’s disease. Am J Gastroenterol 1993;88:1198–205.

    PubMed  CAS  Google Scholar 

  24. Present DH, Korelitz BI, Wisch N, et al. Treatment of Crohn’s disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Engl J Med 1980;302:981–7.

    Article  PubMed  CAS  Google Scholar 

  25. Colonna T, Korelitz BI. The role of leukopenia in 6-mercaptopurine-induced remission of refractory Crohn’s disease. Am J Gastroenterol 1993;89:362–6.

    Google Scholar 

  26. Lennard L, Rees CA, Lilleyman JS, et al. Childhood leukemia: a relationship between intracellular 6-mercaptopurine metabolites and neutropenia. Br J Clin Pharmacol 1993;16:359–63.

    Google Scholar 

  27. Zimm S, Collins JM, Riccardi R, et al. Variable bioavailability of oral mercaptopurine. Is maintenance chemotherapy in acute lymphoblastic leukemia being optimally delivered. Ann 1983;308:1005–9.

    CAS  Google Scholar 

  28. McLeod HL, Relling MV, Liu Q, Pui CH, Evans WE. Polymorphic thiopurine methyl transferase in erythrocytes is indicative of activity in leukemic blasts from children with acute lymphoblastic leukemia. Blood 1995;1887–902.

    Google Scholar 

  29. Christie NT, Drake S, Meyn RE. 6-thioguanine induced DNA damage as a determinant of cytotoxicity in cultured hamster ovary cells. Cancer Res 1986;44:3665–71.

    Google Scholar 

  30. Fairchild CR, Maybaum J, Kennedy KA. Concurrent unilateral chromatid damage and DNA strand breaks in response to 6-thioguanine treatment. Biochem Pharmacol 1986;35:3533–41.

    Article  PubMed  CAS  Google Scholar 

  31. Alves S, Prata MJ, Ferreira F, Amorim A. Screening of thiopurine methyl s-transferase mutations by horizontal conformation-sensitive gel electrophoresis. Human Mutation 2000;15:246–53.

    Article  PubMed  CAS  Google Scholar 

  32. Evans WE, Horner M, Chu YQ, et al. Altered mercaptopurine metabolism, toxic effects, and dosage requirements in a thiopurine methyltransferase deficient child with acute lymphoblastic leukemia. J Pediatr 1991;119:985–9.

    Article  PubMed  CAS  Google Scholar 

  33. McLeod HL, Krynetski EY, Relling MV, et al. Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia 2000;14:567.

    Article  PubMed  CAS  Google Scholar 

  34. Cuffari C, Theoret Y, Latour S, et al. 6-mercaptopurine metabolism in Crohn’s disease: correlation with efficacy and toxicity. Gut 1996;39:401–6.

    Article  PubMed  CAS  Google Scholar 

  35. Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Theoret Y, Seidman EG. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000;118;705–13.

    Google Scholar 

  36. Achar JP, Stevens T, Brzezinski A, Seidner D, Lashner B. 6-Thioguanine levels versus white blood cell counts in guiding 6-mercaptopruine and azathioprine therapy. Am J Gastroenterol 2000;95:A272.

    Article  Google Scholar 

  37. Cuffari C, Hunt S, Bayless TM. Utilization of erythrocyte 6-thioguanine metabolite levels to optimize therapy in IBD. Gut 2001;48:642–6.

    Article  PubMed  CAS  Google Scholar 

  38. Gupta P, Gokhlae R, Kirschner BS. 6-mercaptopurine metabolite levels in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2001;33:450–4.

    Article  PubMed  CAS  Google Scholar 

  39. Belaiche J, Desager JP, Horsman Y, Louis E. Therapeutic drug monitoring of azathioprine and 6-mercaptopurinemetabolites in Crohn’s disease. Scand J Gastroenterol 2001;36:71–6.

    Article  PubMed  CAS  Google Scholar 

  40. Lowry PW, Franklin CL, Weaver AL, Szumlanski C, Mays DC, Loftus EV, Tremaine WJ, Lipsky JJ, Weinshilboum RM, Sandborn WJ. Leukopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine or balsalazide. Gut 2001;49:656–64.

    Article  PubMed  CAS  Google Scholar 

  41. Goldenberg BA, Rawsthorne P, Berstein CN. The utility of 6-thioguanine metabolite levels in managing patients with inflammatory bowel disease. Am J Gastroenterol 2004;99:1744–8.

    Article  PubMed  CAS  Google Scholar 

  42. Cuffari C, Dassoupolus T. Bayless TM. Thiopurine methyl-transferase activity influences clinical response to azathioprine therapy in patients with IBD. Clin Gastroenterol Hepatol 2004;2:410–17.

    Article  PubMed  CAS  Google Scholar 

  43. Kaskas BA, Louis E, Hinderof U, et al. Safe treatment of thiopurine S-transferase deficient Crohn’s disease patients with azathioprine. Gut 2003;52:140–2.

    Article  PubMed  CAS  Google Scholar 

  44. Dubinsky MC, Yang H, Hassard PV, Seidman EG, Kam LY, Abreu MT, Targan SR, Vasiliauskas E. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002;122:904–15.

    Article  PubMed  CAS  Google Scholar 

  45. Sparrow MP, Hande SA, Friedman S, et al. Allopurinol safely and effectively optimizes thioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine. Aliment Pharmacol Ther 2005;22:441–6.

    Article  PubMed  CAS  Google Scholar 

  46. Black AJ, McLeod HL, Capell HA. Thiopurine methyl transferase predicts therapy-limitingsever toxicity from azathioprine. Ann Intern Med 1998;129:716–18.

    PubMed  CAS  Google Scholar 

  47. Colombel JF, Ferrari N, Debuysere H, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000;118(6):1025–30.

    Article  PubMed  CAS  Google Scholar 

  48. Bo J, Schroder H, Kristinsson J, Possible carcinogenic effect of 6-mercaptopurine on bone marrow stem cells: relation to thiopurine metabolism. Cancer 1999;86:1080–6.

    Article  PubMed  CAS  Google Scholar 

  49. Garza A, Sninsky CA. Changes in red cell mean corpuscular volume (MCV) during azathioprine or 6-mercaptopurine therapy for Crohn’s disease may indicate optimal dose titration. Gastroenterology 2001;120:A3166.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Gastroenterology, The Johns Hopkins Hospital, 600 N. Wolfe St., Brady 308, Baltimore, MD 21287, USA

    Carmen Cuffari

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  1. Carmen Cuffari
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Editor information

Editors and Affiliations

  1. Attending Physician, Division of GI Hepatology and Nutrition, Director Endoscopy Suite, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    Petar Mamula M.D. (Assistant Professor of Pediatrics) (Assistant Professor of Pediatrics)

  2. Attending Physician, Children’s Center for Digestive Health, Greenville Hospital System University Medical Center, University of South Carolina School of Medicine, Greenville, South Carolina, USA

    Jonathan E. Markowitz M.D., M.S.C.E. (Associate Professor of Clinical Pediatrics) (Associate Professor of Clinical Pediatrics)

  3. Attending Physician and Director, Inflammatory Bowel Disease Center Division of GI, Hepatology and Nutrition. The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    Robert N. Baldassano M.D. (Professor) (Professor)

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Cuffari, C. (2008). 6-Mercaptopurine Therapy. In: Mamula, P., Markowitz, J.E., Baldassano, R.N. (eds) Pediatric Inflammatory Bowel Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-73481-1_29

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  • DOI: https://doi.org/10.1007/978-0-387-73481-1_29

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-73480-4

  • Online ISBN: 978-0-387-73481-1

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