An expert panel was convened to provide specific, expert consensus guidelines for the use of glucarpidase in patients who develop high‐dose methotrexate (HDMTX)‐induced nephrotoxicity and delayed methotrexate excretion. This guideline provides recommendations to identify the population of patients who would benefit from glucarpidase rescue by more precisely defining the absolute methotrexate concentrations associated with risk for severe or life‐threatening toxicity at several time points after the start of a HDMTX infusion.

Background High-dose methotrexate (HDMTX)-induced acute kidney injury is a rare but life-threatening complication. The methotrexate rescue agent glucarpidase rapidly hydrolyzes methotrexate to inactive metabolites. We retrospectively reviewed glucarpidase use in pediatric cancer patients at our institution and evaluated whether subsequent resumption of HDMTX was tolerated. Methods Clinical data and outcomes of all patients who received glucarpidase after HDMTX administration were reviewed. Results Of 1,141 patients treated with 4,909 courses of HDMTX, 20 patients (1.8% of patients, 0.4% of courses) received 22 doses of glucarpidase. The median glucarpidase dosage was 51.6 units/kg (range, 13 – 65.6 units/kg). At the time of administration, the median plasma methotrexate concentration was 29.1 µM (range, 1.3 – 590.6 µM). Thirteen of the 20 patients received a total of 39 courses of HDMTX therapy after glucarpidase. The median time to complete methotrexate excretion was 355 hours (range, 244 – 763 hours) for the HDMTX course during which glucarpidase was administered, 90 hours (range, 66 – 268 hours) for the next HDMTX course, and 72 hours (range, 42 – 116 hours) for subsequent courses. The median peak serum creatinine during these HDMTX courses was 2.2 mg/dL (range, 0.8 – 9.6 mg/dL), 0.8 mg/dL (range, 0.4 – 1.6 mg/dL), and 0.6 mg/dL (range, 0.4 – 0.9 mg/dL), respectively. One patient experienced nephrotoxicity upon rechallenge with HDMTX. Renal function eventually returned to baseline in all patients and no patient died as a result of methotrexate toxicity. Conclusion It is possible to safely resume HDMTX therapy after glucarpidase treatment for HDMTX-induced acute kidney injury.

Background-Improved cure rates for childhood acute lymphoblastic leukemia over the past 2 decades have allowed greater attention to patients' quality of life. Neuropathic pain is an unpleasant side effect of chemotherapeutic agents for leukemia, especially vincristine.

BACKGROUND Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescent, and young adult patients with cancer. At St. Jude Children’s Research Hospital, the recommended posaconazole dose in patients less than 34 kg is 18–24 mg/kg daily given in 4 divided doses. For patients 13 years and older or those weighing 34 kg or more, the recommended dose is 800 mg daily given orally in four divided doses. OBJECTIVE This study was conducted to determine if the current posaconazole dosing guidelines achieved target posaconazole plasma concentrations of ≥ 0.7 μg/mL. METHODS We examined data from patients who received treatment-dose posaconazole with at least one posaconazole plasma concentration measurement. RESULTS Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5–23.2 years). Twenty-one patients out of 33 (63.6%) had posaconazole concentrations of ≥ 0.7 μg/mL (median 1.4 μg/mL; range 0.7–2.98 μg/mL) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg per day. Patients with concentrations < 0.7 μg/mL (median 0.4 μg/mL; range 0.025–0.69 μg/mL) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg per day; p = 0.02). Of the 12 patients with concentrations < 0.7 μg/mL, seven (58.3%) were 13 years of age or older. CONCLUSIONS The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients < 13 than those > 13 years of age. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent and young adult cancer patients with routine therapeutic drug monitoring in all patients to ensure adequate concentrations.