Using this approach, retrospective clinical data from our patient population has identified a significant number of HDMTX treatments associated with delayed MTX excretion (defined as a MTX level of >1 µmol/L at 42 hours and > 0.40 µmol/L at 48 hours) and secondary toxicity. From January 2012-May 2013, 16 ALL patients received 64 total HDMTX doses (4 cycles each). At 48 hours post-HDMTX infusion, 27 doses (42%) exhibited delayed MTX clearance [median plasma MTX level 0.41 µmol/L (range, 0.01-1.6 µmol/L) above the 48-hour clearance level of 0.40 µmol/L]. Mucositis, cytopenias, skin rashes, and subsequent chemotherapy delays were noted in 31%, 31%, 6%, and 34% of doses respectively. Toxicities in combination with delayed MTX clearance occurred in 17 doses (27%) and toxicity without delayed clearance occurred in 18 doses (28%). Also, a mean increase in sCr of 17% (range 0-57.6%) above pre-HDMTX baseline was observed. Although measurements of sCr are used per the standard of care as an indirect marker of kidney injury, the known delay in sCr rise following nephrotoxic (drug-induced) kidney injury (KI) eliminates its use as a point of care surrogate marker for kidney toxicity. Therefore, this study seeks to identify more sensitive markers of kidney injury that could serve as better predictors of delayed excretion and/or toxicity of HDMTX. This study is a pilot repeated-measures feasibility study.