Pediatric Oncology Subcommittee of Oncologic Drugs Advisory Committee





The following background readings are intended to facilitate the discussion.


Thiopurine Methyltransferase and 6-Mercaptopurine Metabolism


1.      Current Product Label Purinethol


2.      Lennard L, Gibson BES, Nicole T, Lilleyman JS.

Congenital Thiopurine Methyltransferase Deficiency And 6-Mercaptopurine Toxicity During Treatment For Acute Lymphoblastic Leukemia. Arch Dis Child. 69:577-579. 1993;


3.      Yates C, Krynetski EY, Loennechen, T Fessing M; Tai, H-L Pui C-H, Relling MV Evans WE

Molecular Diagnosis Of Thiopurine S-Methyltransferase Deficiency: Genetic Basis For Azathioprine And Mercaptopurine Intolerance. Annals of Internal Medicine 126:608-614. 1997


4.      Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui C-H, Evans WE

Mercaptopurine Therapy Intolerance and Heterozygosity at the Thiopurine S-Methyltransferase Gene Locus, Journal of The National Cancer Institute, 91 (23): 2001-20081999


5.      Evans WE, Hon YY, Bomgaars L, Coutre S, Holdsworth M, Janco R, Kalwinsky D, Keller F, Khatib Z, Margolin J, Murray J, Quinn J, Ravindranath Y, Ritchey K, Roberts W, Rogers ZR, Schiff D, Steuber C, Tucci F, Kornegay N, Krynetski EY, Relling MV

Preponderance of Thiopurine S-Methyltransferase Deficiency and Heterozygosity among Patients Intolerant to Mercaptopurine or Azathioprine. J Clin Oncol 19:2293-2301, 2001


6.      Weinshilboum R

Thiopurine Pharmacogenetics: Clinical and Molecular Studies of Thiopurine Methyltransferase

Drug Metabolism and Disposition Vol. 29, No. 4, Part 2, 601-605, 2001


7.      Lancaster DL, Patel N, Lennard L LilleymanJS

6-Thioguanine in children with acute lymphoblastic leukaemia: Influence of food on parent drug pharmacokinetics and 6-thioguanine nucleotide concentrations. J Clin Pharmacol, 51, 531-539 2001


8.      Lennard L, Lewis IJ, Michelagnoli M, Lilleyman JS

Thiopurine Methyltransferase Deficiency in Childhood Lymphoblastic Leukaemia: 6-Mercaptopurine Dosage Strategies. Med. Pediatr. Oncol. 29:252255, 1997


9.      Lennard L , S. Chew T Lilleyman JS

Human thiopurine methyltransferase activity varies with red blood cell age. J Clin Pharmacol, 52, 539-546 2001

Pediatric Oncology Subcommittee of Oncologic Drugs Advisory Committee


Bibliography Continued



Principles for International Cooperative Studies


10.   Nuremberg Code,1949


11.   Belmont Report, 1979


12.   American Academy of Pediatrics Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations, 1995


13.   American Academy of Pediatrics Informed Consent, Parental Permission, and Assent in Pediatric Practice, 1995


14.   National Institutes of Health Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects, 1998


15.   Royal College of Paediatrics (U.K.) and Child Health Ethics Advisory Committee: Guidelines for the conduct of medical research involving children, 2000


16.   International Conference on Harmonization Efficacy Document 11: Clinical Investigation of Medicinal Products in the Pediatric Population


17.   National Bioethics Advisory Committee Ethical and Policy Issues in Research Involving Human Participants, 2001


18.   World Medical Association, Declaration of Helsinki, Ethical Principles for Medical Research Involving Human Subjects, 2002