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.