2.1. Study design
This was a single center, retrospective cohort study of pediatric oncology patients at the University of North Carolina Medical Center (UNCMC) from April 1, 2014, through May 31, 2022. Eligibility criteria included patients aged 0 to 18 years who received their full maintenance treatment for B-cell or T-cell ALL at the UNCMC Pediatric Oncology Department and had 6MMP and 6TGN levels collected during maintenance therapy to assess for skewed metabolism. Exclusion criteria included a diagnosis of non-B-cell or T-cell leukemia (i.e., MPAL, NK-cell ALL, lymphoblastic lymphoma), metabolites drawn outside of maintenance therapy, metabolites collected only to assess non-adherence with therapy, or if any part of maintenance therapy was received at an outside hospital.
Patients were initially identified by UNCMC Pharmacy Analytics based on the pre-specified inclusion and exclusion criteria. Data were manually extracted from the institutional electronic medical record (EMR) for each patient from the beginning of maintenance therapy until the end of chemotherapy or May 31, 2022, whichever came first. UNCMC did not have a written institutional protocol for the initiation of allopurinol for skewed metabolism at the time of this study. Patients were started on allopurinol at the discretion of the primary oncologist. Common practice for the starting dose of allopurinol at UNCMC was 50 mg/m2, which was either rounded to the nearest tablet size or administered as an exact dose using a compounded oral suspension.12 This dosing was based on the recommendations from Brackett, et al.4 Generally, initiation of allopurinol was considered when patients displayed skewed metabolites along with inadequate myelosuppression, hepatotoxicity and/or other undesirable side effects associated with 6MP such as rash, hypoglycemia, and GI upset.