3.1. Patient Characteristics
One-hundred and seventeen pediatric subjects with a diagnosis of B-cell or T-cell ALL who had 6MMP and 6TGN metabolites drawn during maintenance therapy were identified by the UNCMC Pharmacy Analytics team. Twenty-two patients were deemed ineligible for final analyses, including subjects with metabolites drawn only to assess medication non-adherence (n=12), subjects who received a portion of their ALL maintenance therapy at an institution outside UNCMC (n=5), subjects who had metabolites drawn outside of maintenance therapy (n=3), a subject with allopurinol initiated outside of the study time frame (n=1), and a subject who was >18 years-old at the time of allopurinol initiation (n=1). Ultimately, a total of 95 patients met study inclusion criteria with 32 patients receiving allopurinol for management of skewed 6MP metabolism during their maintenance therapy (34%) (Figure 1).
There were no significant differences in baseline demographics between the allopurinol cohort and the standard treatment cohort (Table 1). The average age at the start of maintenance in the allopurinol cohort was 7 years and 5 years in the standard treatment cohort. Fifty-six percent were female in the allopurinol cohort and 44% were female in the standard treatment cohort, while most patients in both cohorts self-identified as White.
Among the 32 patients in the allopurinol cohort, the median time point for allopurinol initiation was on day 218, corresponding to maintenance cycle 3, day 48. The average dose of 6MP prior to allopurinol initiation was 83 (+ 16) mg/m2/day, which was decreased to an average dose of 37 (+ 10) mg/m2/day after allopurinol initiation. The average dose of allopurinol was 63 (+ 19) mg/m2/day. The rationale for initiating allopurinol was inadequate myelosuppression (50%), followed by hepatotoxicity (43%), GI upset (22%), rash (13%), or other clinical reasons (16%). Rational for allopurinol initiation was not mutually exclusive, and patients often had more than one reason for therapeutic intervention.