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.