This application will involve two parts examining the relationship of cancer chemotherapy pharmacokinetics with disease-specific outcome. They involve the analysis of RBC's for thiopurine metabolites in patients receiving either 6-mercaptopurine (6-MP) or 6-thioguanine (6-TG). If successful, these studies will lead to better understanding on how to utilize these agents more effectively and extend a potential for tailoring chemotherapy based on individual patient biochemistry rather than on empirical formulas. Part 1 will examine the relationship of RBC thiopurine metabolite concentration with outcome (disease-free survival) in patients enrolled on the proposed Children's Cancer Group protocol CCG-1952 for standard acute lymphoblastic leukemia. In addition to standard ALL therapy, these patients will be randomized to receive either oral 6-MP or oral 6-TG during the 2nd through 4th months of therapy followed by oral 6-MP thereafter. This group will determine if oral 6-TG affords a better systemic drug exposure vs. oral 6-MP by quantifying RBC thiopurine metabolite levels, and whether these concentrations correlate with event-free survival. Patients will also be evaluated to determine if a group with """"""""subtherapeutic"""""""" RBC thiopurine metabolite levels can be identified. Part 2 will examine the relationship between RBC thiopurine metabolite levels with outcome in patients enrolled on the proposed CCG/NCI pilot study protocol CCG-1942 for lower risk ALL. In addition to standard therapy, these patients will receive IV 6-TG in place of oral 6-MP during consolidation and interim maintenance chemotherapy, and oral 6-TG in place of oral 6-MP during maintenance chemotherapy. This group will determine if IV 6-TG affords a better systemic drug exposure by quantifying intracellular thiopurine metabolite concentration in RBCs and whether these concentrations correlate with EFS.
