Toxicities
Methotrexate cleared on time in 76.5% of doses (Table 2). The 46 doses which resulted in delayed clearance occurred in 26 patients (56.5%). Of these, methotrexate cleared by hour 72 in 26 doses, with 20 doses clearing beyond hour 72 (range: 84 to 256 hours). Grade ≥3 mucositis occurred following 25 doses of HD-MTX (13% of all doses administered) in 18 patients (39.1%). Serum creatinine elevations occurred during 48 HD-MTX doses (24%) in 27 patients (58.7%). Creatinine elevations were transient and returned to baseline in all patients, due to early recognition and appropriate increases in hydration. Creatinine elevations were significantly associated (p<0.001) with an increased likelihood of delayed clearance (OR=4.44, 95% CI: 1.82-10.84) after accounting for clinical factors. Additionally, creatinine elevations (OR=4.36, 95% CI: 1.44-13.25) and delayed clearance (OR=6.24, 95% CI: 2.17-17.95) were independently associated with subsequent grade ≥3 mucositis. No patient required glucarpidase for methotrexate toxicity or delayed clearance. There was no observed association between race/ethnicity and time to clearance, serum creatinine elevations, or mucositis. There was an observed association (p<0.05) of self-reported Latino ethnicity and shorter time to clearance, as well as a potentially increased time to clearance in patients receiving R-CYM cycles in ANHL01P1 and ANHL1131, and an increased risk of serum creatinine elevations observed during methotrexate in patients receiving courses of R-COPADM in ANHL01P1 and ANHL1131.