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.