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J Pediatr Hematol Oncol. 2015 Apr;37(3):e206-9. doi: 10.1097/MPH.0000000000000246.

Pharmacokinetics of 6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of Childhood ALL: Hypothesis and Case Report.

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*Department of Pediatrics and Adolescent Medicine, The University Hospital Rigshospitalet †The Faculty of Medicine, Institute of Gynecology, Obstetrics and Pediatrics, University of Copenhagen, Copenhagen, Denmark.


Methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia is challenged by treatment-related hepatotoxicity, failure to achieve the myelosuppressive target, and lack of direct parameters for monitoring treatment efficacy or even intensity. Patients with low thiopurine methyltransferase (TPMT) activity have lower levels of hepatotoxic methylated thiopurine metabolites (MeMPs), higher levels of thioguanine nucleotides (TGNs), and reduced relapse rates. Addition of 6-thioguanine to maintenance therapy of a child with ALL and high TPMT activity increased the TGN/MeMP index in erythrocytes 5.5-fold, mimicking the more favorable thiopurine metabolism seen in patients with low TPMT activity.

[Indexed for MEDLINE]

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