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Pediatric Oncology Group (POG) protocol 9605, a phase III study of standard risk acute lymphoblastic leukemia (ALL), was designed in part to compare daily (QD) versus twice-daily (BID) mercaptopurine (MP) dosing during intensification and continuation therapy. 1082 patients were enrolled between 1996 and 1999. MP is an important antimetabolite in the treatment of ALL. Due to its S-phase dependence and short half-life, dosing frequency may be crucial to toxicity and/or efficacy. MP is converted into two major metabolites, 6-thioguanine (TGN) and 6-methylthioinosinic acid (mMP). Correlations of toxicity and dose frequency were tabulated. Red blood cell (RBC) TGN and mMP levels measured in a randomized subpopulation (226/1082 patients) on POG 9605 found markedly elevated mMP in the QD versus BID group (2020 versus 1275 ng/8x10⁸ RBC) with slightly higher levels of TGN in the QD group (42 …