Use of Allopurinol to Manage Skewed 6-Mercaptopurine Metabolism in
Pediatric Maintenance Acute Lymphoblastic Leukemia Treatment
Abstract
Background: 6-Mercaptopurine is a cornerstone of maintenance
therapy for pediatric ALL. Response to 6MP is typically determined by
the ANC. Therapeutic ANC range while receiving 6MP is between
500-1,500/µL. In addition to desired myelosuppression, 6MP is associated
with multiple adverse drug effects. Increased doses of 6MP can lead to
therapeutic ANC values; however, patients may experience adverse effects
before obtaining therapeutic myelosuppression, often deemed “skewed
metabolism.” Allopurinol may potentially correct skewed 6MP metabolism.
Procedure: Pediatric patients with ALL with 6MMP and 6TGN
metabolites drawn during maintenance therapy were analyzed for
allopurinol use. The primary outcome evaluated the percentage of time
spent in therapeutic ANC range before and after allopurinol initiation.
Additionally, the difference in 6MMP:6TGN ratios before and after
allopurinol initiation, incidence of hepatotoxicity, and rates of
relapse, were analyzed. Results: Ninety-five patients were
included for analysis. Thirty-two (34%) patients received allopurinol.
There were no significant differences in baseline demographics between
the patients who received allopurinol and those who did not. When
comparing ANC values pre- and post- allopurinol initiation, a
statistically significant increase in the percentage of time spent in
therapeutic range was observed (27% vs. 43%; P=0.03).
Additionally, when comparing metabolite ratios pre- and post-allopurinol
initiation, a statistically significant decrease in 6MMP:6TGN metabolite
ratio values was observed (86.7 vs 3.6; P < 0.0001).
Conclusions: Allopurinol significantly increased the percent time
in therapeutic ANC range and can be safely utilized to significantly
lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable
side effects of 6MMP, and optimizing the anti-leukemic effects
associated with 6TGN.